Enzyme-Programmed Self-Assembly of Nanoparticles.

Nanoparticles are a hot topic in the field of nanomaterial research due to their excellent physical and chemical properties. In recent years, DNA-directed nanoparticle self-assembly technology has been widely applied to the development of numerous complex nanoparticle superstructures. Due to the inherent stability and surface electric repulsion of nanoparticles, it is difficult to make nanoparticle superstructures respond to molecular signals in the external environment. In fact, enzyme-programmed molecular systems are developed to allow diverse functions, including logical operations, signal amplification, and dynamic assembly control. Therefore, combining enzyme-controlled DNA systems may endow nanoparticle assembly systems with more flexibility in program design, allowing them to respond to a variety of external signals. In this review, we summarize the basic principles of enzyme-controlled DNA/nanoparticle self-assembly and introduce its applications in heavy metal detection, gene expression, proteins inside living cells, cancer cell therapy, and drug delivery. With the continuous development of new nanoparticle materials and the increasing functionality of enzyme DNA circuits, enzyme-directed DNA/nanoparticle self-assembled probe technology is expected to see significant future development.

Leukocyte telomere length mediates the association between cadmium exposure and cognitive function in US older adults.

BACKGROUND: Long-term exposure to cadmium-polluted environments may lead to shortened leukocyte telomere length and cognitive decline. This study aims to investigate (1) the associations among blood cadmium levels, leukocyte telomere length, and cognitive function, and (2) the mediating role of leukocyte telomere length between blood cadmium levels and cognitive function among older adults in the United States. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Cadmium exposure level was assessed by measuring cadmium levels in blood samples. Leukocyte telomere length was measured by quantitative polymerase chain reaction, and cognitive function was measured by the digit symbol substitution test (DSST). RESULTS: A total of 2185 older adults aged over 60 were included in this study, comprising 1109 (49.65%) males. Elevated blood cadmium levels were significantly associated with the risk of a decline in cognitive function (ß = - 2.842, p = 0.018). Shorter leukocyte telomere lengths were significantly associated with a higher risk of a decline in cognitive function (ß = 4.144, p = 0.020). The total indirect effect on the blood cadmium level and cognitive function via leukocyte telomere length was - 0.218 (p = 0.012). The mediation effect was estimated to be 0.218/2.084 × 100% = 10.46%. CONCLUSION: The findings suggest that cadmium exposure may increase the risk of cognitive impairment by causing shortened leukocyte telomere length.

Iruplinalkib (WX­0593), a novel ALK/ROS1 inhibitor, overcomes crizotinib resistance in preclinical models for non-small cell lung cancer.

Despite remarkable initial responses of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC) patients, cancers eventually develop resistance within one to two years. This study aimed to compare the properties of iruplinalkib (WX­0593) with other ALK inhibitors and report the comprehensive characterization of iruplinalkib against the crizotinib resistance. The inhibitory effect of iruplinalkib on kinase activity was detected. A kinase screen was performed to evaluate the selectivity of iruplinalkib. The effect of iruplinalkib on related signal transduction pathways of ALK and c-ros oncogene 1 (ROS1) kinases was examined. The cellular and in vivo activities of ALK inhibitors were compared in engineered cancer-derived cell lines and in mice xenograft models, respectively. Human hepatocytes derived from three donors were used for evaluating hepatic enzyme inducing activity. HEK293 cell lines expressing transportors were used to invesigated the drug interaction potential mediated by several transporters. The results showed iruplinalkib potently inhibited the tyrosine autophosphorylation of wild-type ALK, ALKL1196M, ALKC1156Y and epidermal growth factor receptor (EGFR)L858R/T790M. The inhibitory effects of iruplinalkib in patient-derived xenograft and cell line-derived xenograft models were observed. Moreover, iruplinalkib showed robust antitumor effects in BALB/c nude mice xenograft models with ALK-/ROS1-positive tumors implanted subcutaneously, and the tumor suppressive effects in crizotinib-resistant model was significantly better than that of brigatinib. Iruplinalkib did not induce CYP1A2, CYP2B6 and CYP3A4 at therapeutic concentration, and was also a strong inhibitor of MATE1 and MATE2K transporters, as well as P-gp and BCRP. In conclusion, iruplinalkib, a highly active and selective ALK/ROS1 inhibitor, exhibited strong antitumor effects in vitro and in crizotinib-resistant models.

A Strategy for Rapid Discovery of Marker Peptides Associated with Fibrinolytic Efficacy of Pheretima aspergillum Based on Bioinformatics Combined with Parallel Reaction Monitoring.

Quality control of animal-derived traditional Chinese medicines has improved dramatically as proteomics research advanced in the past few decades. However, it remains challenging to identify quality attributes with routine proteomics approaches since protein with fibrinolytic activity is rarely reported in pheretima, a typical animal-derived traditional medicine. A novel strategy based on bioinformatics combined with parallel reaction monitoring (PRM) was developed here to rapidly discover the marker peptides associated with a fibrinolytic effect. Potential marker peptides were found by lumbrokinase sequences' alignment and in silico digestion. The fibrinogen zymography was used to visually identify fibrinolytic proteins in pheretima. As a result, it was found that the fibrinolytic activity varied among different portions of pheretima. Fibrinolytic proteins were distributed regionally in the anterior and anterior-mid portion and there was no significant fibrinogenolytic activity observed in the mid-posterior and posterior portion. Finally, PRM experiments were deployed to validate and quantify selected marker peptides and a total of 11 peptides were identified as marker peptides, which could be potentially used in quality control of pheretima. This strategy provides a robust workflow to benefit the quality control of other animal-derived traditional medicines.

Application of PET/CT in Preoperative Evaluation and Diagnosis of Gastric Cancer.

The aim study to study the significance of pet clinical examination image technology for early gastric mucosal adenocarcinoma, improve the accuracy and accuracy of image examination results of gastric cancer, and provide important reference significance and value for early treatment. Study methods, we used the experimental method of clinical medicine to obtain some reference data through the intervention of different image examinations on experimental patients of different groups and stages, These data show that the use of PET-CT imaging can improve the one-year survival rate of patients and reduce the one-year recurrence rate. Lymphatic metastasis rate and hematogenous metastasis rate, so as to highlight the advantages of PET-CT imaging.

Herpetic uveitis caused by herpes simplex virus after cataract surgery in a patient without prior viral keratitis or uveitis: a case report.

BACKGROUND: To report a case of herpetic uveitis caused by herpes simplex virus after cataract surgery in a patient without prior viral keratitis or uveitis. CASE PRESENTATION: A 70-year-old female was referred to our clinic with a 16-day history of acute blurry vision with painful redness in the right eye. She accepted cataract surgery for the right eye ten days before initial of ocular symptoms. There was significant inflammation in anterior chamber of the right eye. Retina exam showed moderate dense vitreous opacity but not necrotic or focal retinal lesion in the right eye. The aqueous humor collected from the right eye was positive for herpes simplex virus (HSV) DNA by PCR. The diagnosis of herpetic uveitis in the right eye was made due to clinical presentations and aqueous humor examination. CONCLUSION: Herpetic virus reactivation might occasionally occur after intraocular surgery in patients without prior ocular viral diseases, inducing atypical postoperative intraocular inflammation.

Dielectric Surface Flashover under Long-Term Repetitive Microsecond Pulses in Compressed Gas Environment.

As a key component of a high-power microwave (HPM) system, a multi-gap gas switch (MGS) has recently developed insulation failure due to surface flashover. Although design criteria for surface insulation have been put forward, it is still not clear how the insulation in this case deteriorated under long-term repetitive microsecond pulses (RMPs). In this paper, flashover experiments under RMPs were carried out on various dielectric surfaces between parallel-plane electrodes in SF6 and air atmospheres, respectively. Based on tests of the surface insulation lifetime (SIL), an empirical formula for SIL prediction is proposed with variations of insulator work coefficient λ, which is a more suitable parameter to characterize SIL under RMPs. Due of the accumulation effect, the relationship between E/p and ptdelay varies with the pulse repetitive frequency (PRF) and SIL recovery capability decreases with an increase in PRF and surface deterioration is exacerbated during successive flashovers. It is concluded that the flashover path plays a crucial role in surface insulation performance under RMPs due to the photoemission induced by ultraviolet (UV) radiation, signifying the necessity of reducing surface paths in future designs as well as the improvement of surface insulation.

Deployment of a bioabsorbable plate as the rigid buttress for skull base repair after endoscopic pituitary surgery.

BACKGROUND: Bioresorbable alloplastic implants have become desirable as a rigid buttress for reconstructing skull base defects. This study aimed to describe the use of a biodegradable plate (PolyMax RAPID) in skull base repair of endoscopic endonasal pituitary surgery and to investigate the clinical outcome and safety of this novel method. METHODS: Between January 2019 and January 2020, 22 patients with pituitary adenomas who underwent endoscopic skull base repair with a Polymax RAPID plate were included. After endonasal transsphenoidal surgery, a trimmed bioresorbable plate was placed in the position between the dura and the bone of the skull base to reconstruct the sellar floor and buttress the pituitary gland and sellar packing. The patient demographics, radiologic imaging, and postoperative outcomes were carefully reviewed. All patients were followed up by a routine nasal endoscopic assessment and radiologic examinations. RESULTS: The present study comprised 10 (45.5%) males and 12 (54.4%) females with an average age of 51.9 years. There were 7 (31.8%) growth hormone (GH) secreting adenomas, 2 (9.1%) thyroid stimulating hormone (TSH) secreting adenomas, and 13 (59.1%) non-functioning adenomas. Enlarged sellar floor and paranasal sinusitis were seen in 13 (59.1%) and 11 (50.0%) cases shown by preoperative computed tomography (CT) or magnetic resonance imaging (MRI), respectively. There were 6 (27.3%) grade-1 and 16 (72.7%) grade-0 cases by intraoperative cerebrospinal fluid (CSF) leak grading. None of these patients received lumbar drains postoperatively and no postoperative CSF rhinorrhea was detected in our series. The PolyMax RAPID plates which could be clearly identified on postoperative CT or sagittal T1-weighted MRI were shown to provide an ideal rigid buttress for sellar repair. CONCLUSIONS: The Polymax RAPID plate can be an optimal implant to achieve rigid repair of sellar floor defects after endonasal transsphenoidal pituitary surgery.

Cryptotanshinone ameliorates cardiac injury and cardiomyocyte apoptosis in rats with coronary microembolization.

Coronary microembolization (CME) is a prevalent cardiovascular disease, especially nowadays when percutaneous coronary intervention is widely applied. However, neither cardio-protective agents nor devices for distal protection could effectively prevent the occurrence of CME. Therefore, we aimed to develop a new drug for CME. Rats were orally administrated with different doses of Cryptotanshinone (CTS, 5, 15, 45 mg/kg) daily for 2 weeks, respectively, following CME surgery. Then cardiac function and cardiac injury were evaluated in CME rats as well as measuring oxidative stress and apoptosis in cardiomyocytes. Compared to sham group, CME operation induced cardiac dysfunction, cardiac injury, the activation of platelet and endothelium, cardiomyocyte apoptosis and oxidative stress, all of which could be dose-dependently restored by CTS pretreatment. Moreover, NF-κB signaling pathway participated in the development of CME and also in the preventive process of CTS against CME. CTS might serve as a potential and promising candidate drug to prevent the occurrence of CME.

Risk Factors of Recurrent Retinal Detachment Following Surgical Treatment for Rhegmatogenous Retinal Detachment: A Retrospective Study.

OBJECTIVE: To identify potential risk factors for recurrent retinal detachment after surgical treatment for rhegmatogenous retinal detachment with choroidal detachment (RRD-CD) in a Chinese population. METHODS: A total of 1212 patients with RRD-CD admitted to Beijing Tongren Hospital from 2004 to 2018 were reviewed retrospectively. The rate of recurrent retinal detachment was calculated, and risk factors were analyzed by logistic regression analysis. RESULTS: The average age of the patients was 48.51 years, 760 patients (62.7%) were male, and 630 patients (52.0%) had right eye disease. The recurrence rate in the same eye was 21.3%. The incidence of recurrence retinal detachment was higher in patients who were male, middle age, and with poor preoperative vision, longer axial length, and scleral buckling. Recurrence usually occurred 3 months after surgery. CONCLUSION: Male, middle age, longer axial length, and scleral buckling could be risk factors for recurrent retinal detachment following surgical treatment in patients with RRD-CD.

Elevated Level of miR-551b-5p is Associated With Inflammation and Disease Progression in Patients With Severe Acute Pancreatitis.

Circulating microRNAs have the potential to be noninvasive biomarkers for assessing disease progression. MicroRNA-551b-5p (miR-551b-5p) was previously reported to be differentially expressed in pancreatic patients. The serum miR-551b-5p level was measured in patients with mild acute pancreatitis (MAP), severe acute pancreatitis (SAP), and healthy controls using quantitative real-time polymerase chain reaction (RT-PCR) analysis to evaluate its impact on inflammatory response. Acute Physiology and Chronic Health Evaluation II (APACHE II), Multiple Organ Dysfunction Score (MODS), Sequential Organ Assessment Score (SOFA), and Ranson's scores were recorded. Inflammatory cytokines, IL-6, IL-17, IL-1ß, and Tumor Necrosis Factor-α (TNF-α), were detected in serum samples obtained from MAP and SAP patients on admission day 1, day 3, and day 5 using Enzyme Linked Immunosorbent Assay (ELISA). Inflammatory cytokines were analyzed in peripheral blood mononuclear cells (PBMCs), which were transfected with miR-551b-5p-negative controls and inhibitors. The serum miR-551b-5p level was significantly higher in MAP and SAP patients compared to controls (P < 0.001). An elevated miR-551b-5p level is positively associated with APACHE II, MODS, SOFA, and Ranson's scores (P < 0.001). Serum cytokines levels were significantly elevated in MAP and SAP patients compared to controls (P < 0.05). In addition, the level of these inflammatory cytokines was increased in PBMCs of SAP patients in comparison with those of healthy controls (P < 0.05), and this rise was significantly reduced with the addition of an miR-551b-5p inhibitor. In conclusion, serum miR-551b-5p is elevated in patients with MAP and SAP and is involved in the regulation of inflammatory response. It may be a useful biomarker for assessing the severity of SAP.

Optical Coherence Tomographic Features and Visual Prognosis after Treatment for Idiopathic Choroidal Neovascularization.

BACKGROUND: The aim of this study was to determine whether pretreatment spectral-domain optical coherence tomographic (SD-OCT) features are associated with visual prognosis after treatment for idiopathic subfoveal choroidal neovascularization (ISCNV) with intravitreal ranibizumab. METHODS: We retrospectively evaluated SD-OCT images of eyes with ISCNV undergoing treatment with intravitreal ranibizumab with a mean follow-up of 7 months. RESULTS: This study included 22 patients (22 eyes) with a mean age of 32.7 ± 8.1 years. In univariate analysis, better final visual acuity expressed in logMAR units was significantly associated with a lower amount of pretreatment ellipsoid zone defects (p = 0.03; standardized correlation coefficient ß = 0.46) and a lower amount of pretreatment external limiting membrane (ELM) damage (p = 0.007; ß = 0.56). All other SD-OCT parameters were not significantly associated with final visual acuity. A higher improvement in visual acuity was marginally significantly associated with larger pretreatment ellipsoid zone defects (p = 0.049; ß = -0.43). CONCLUSIONS: The integrity of the outer retinal layers at baseline, in particular of the ELM, is of importance in predicting the final visual outcome in patients undergoing intravitreal medical therapy for ISCNV.

[Application of the pedicle screw in the subaxial cervical spine].

OBJECTIVE: To research the clinical application of lower cervical pedicle screw fixation procedure. METHODS: From September 2011 to July 2013,32 patients underwent posterior pedicle screw-rod system fixation were retrospective analyzed includinig 20 males and 12 females with an average age of 56.4 years old ranging from 21 to 78 years. Among them, 10 patients were traumatic cervical spinal injury, 9 patients were cervical spinal canal tumors, 7 cases were posterior longitudinal ligament ossification of cervical vertebrae, 6 cases were multiple segmental cervical spondylopathy. Preoperatively, X-ray, computed tomography, magnetic resonance imaging and magnetic resonance angiography of the vertebral artery were performed in all patients. After the operation and during the follow-up,X-ray and computed tomography were performed to confirm the pedicle screw position. The accuracy of the pedicle screw placement was evaluated by 4 grades classification from Lee. The spinal cord function was assessed by ASIA impairment scale for traumatic patients and JOA score for non traumatic patients. RESULTS: Totally 144 pedicle screws performed on 32 patients from C3 to C7 involving 132 screws of grade 0,5 screws of grade 1,5 of screws grade 2 and 2 screws of grade 3 according to postoperative CT. There were 12 screws penetrating the pedicle cortex including 8 screws at lateral,2 screws at caudal, 1 screw at medial and 1 screw at cranial. The follow-up time was 12 to 33 months with an average of (21.0±1.5) months. The spinal cord function was not improved in 6 complete cervical spinal cord injury patients,but their paraplegic level descended 1 to 3 segments. Four incomplete cervical spinal cord injury patients' ASIA impairment scale was increased by 1 to 2 grades in average. The JOA score of 22 atraumatic patients increased from preoperative 11.5±0.8 to 15.9±0.6 of postoperative at 6 months (P<0.01). There were no screw loosening,screw pullout and screw-rod breakage. CONCLUSION: The lower cervical pedicle screw fixation can provide excellent 3D stability of the vertebral column. The operation risk and Complication could be minimized by adequate preoperative evaluation for appropriate cases and individual pedicle screw placement. It deserved the clinical expansion.

Subfoveal choroidal thickness change after intravitreal ranibizumab for idiopathic choroidal neovascularization.

PURPOSE: To investigate changes in subfoveal choroidal thickness (SFCT) after intravitreal injections of ranibizumab for idiopathic subfoveal choroidal neovascularization (ISCNV). METHODS: The prospective consecutive case series study included 16 patients with unilateral ISCNV. All eyes with ISCNV were treated with a single intravitreal injection of 0.5 mg ranibizumab followed by as-needed dosing. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography. RESULTS: The mean total follow-up time was 4.9 ± 1.5 months, and the follow-up after the last intravitreal ranibizumab injection was 4.4 ± 1.3 months. In the treated eyes, the SFCT decreased significantly from 354 ± 84 µm at baseline to 328 ± 79 µm at 1 month later (P < 0.001) and reincreased (P = 0.02) to 342 ± 75 µm at the final visit (P = 0.15 versus baseline value). Change in SFCT was marginally (P = 0.11) associated with the change in retinal foveal thickness. In the contralateral unaffected eyes, the SFCT did not change significantly during follow-up (P = 0.76). CONCLUSION: In patients with unilateral ISCNV, intravitreal ranibizumab therapy was associated with a thinning of an abnormally thick subfoveal choroid, marginally in association with a parallel decrease in retinal foveal thickness. It remained elusive whether the choroidal thinning was due to a direct pharmacological effect of ranibizumab or whether it was secondary due to the foveal retinal thinning. In view of the significant differences in SFCT between affected eyes and unaffected contralateral eyes at baseline and in view of the significant therapy-associated decrease in SFCT, the potential role of SFCT as an additional marker for the diagnosis and follow-up of ISCNV and other neovascular maculopathies may be examined in future studies.

Vascular endothelial growth factor in Coats' disease.

PURPOSE: To examine whether vascular endothelial growth factor (VEGF) as one of the most important intraocular cytokines for angiogenesis and increased vascular permeability is associated with Coats' disease. METHODS: The clinical interventional study included 28 patients with Coats' disease and seven control patients with congenital cataract. During intraocular surgery, we obtained aqueous humour samples in which the VEGF concentration was measured by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Coats' disease was graded into four stages. RESULTS: The mean aqueous VEGF level was significantly higher in the Coats' study group than in the control group (158±88 versus 97±21 pg/ml; p=0.002). The VEGF concentrations increased significantly (p<0.001) from 91±32 pg/ml in Coats' disease stage 2 to 100±37 pg/ml in stage 3A1, 185±56 pg/ml in stage 3A2 to 256±93 pg/ml in patients with stage 3B. Vascular endothelial growth factor concentrations in Coats' stage 2 and 3A1 did not differ significantly from the values in the control group. Parallel to the association with the stage of the diseases, the VEGF concentrations were significantly (p<0.001) correlated with extent of exudative retinal detachment. CONCLUSIONS: Increasing severity of Coats' disease is significantly associated with intraocular VEGF concentrations. These results favour the intravitreal application of anti-VEGF drugs as medical therapy of Coats' diseases.

[Analysis of changes of ultrasonic image and hemodynamics of retrobulbar blood vessels in Coats disease].

OBJECTIVE: To analyze the changes of color Doppler flow imaging (CDFI) and hemodynamics of retrobulbar blood vessels in Coats disease. METHODS: It was a prospective and self-comparative study in which 18 cases (18 eyes) were included. Axial eye length was measured with A scan. Routine CDFI was performed in all cases. We examined ophthalmic arteries (OA), central retinal arteries (CRA) and posterior ciliary arteries (PCA) by CDFI, and recorded the peak systolic velocities (PSV), end diastolic velocities (EDV), time averaged maximum velocities (TAMX), pulsatility indexes (PI) and resistance indexes (RI) in all cases. Each hemodynamic parameter in the affected eye (21.36 ± 1.19) mm was compared with those in the contralateral normal eye (controls). T-test was used for the estimation of significance of the difference between the diseased and normal eyes. RESULTS: The axial length in diseased eyes was significantly shorter than that of the controls (22.92 ± 1.09) mm (t = 3.617, P < 0.05). The changes of CDFI in diseased eyes included retinal detachment, retinal cyst, subretinal organization, etc. Vitreoretinal traction, intraocular ossification and calcification were uncommon. The PSV (6.96 ± 1.21) cm/s and EDV (1.99 ± 0.36) cm/s in the diseased eyes were significantly lower than the PSV (8.30 ± 1.46) cm/s and EDV (2.48 ± 0.47) cm/s in the control eyes (t = 2.995, 3.476;P < 0.05). No significance difference was present in other hemodynamic parameters between diseased and normal eyes. CONCLUSIONS: Coats disease is a congenital disease that may influence the development of the eye. The ultrasonography is helpful for the diagnosis and differential diagnosis in Coats disease. Low perfusion of the central optic artery might exist in Coats disease. The hemodynamics changes in Coats disease require further studies.