Peroxidase-mimetic activity of a nanozyme with uniformly dispersed Fe3O4 NPs supported by mesoporous graphitized carbon for determination of glucose.

A Fe3O4/mesoporous graphitized carbon (Fe3O4/m-GC) composite was prepared through a facile calcination method with iron-based metal-organic frameworks (Fe-MOFs) as a sacrificial template. After carbonization, the Fe3O4 nanoparticles were uniformly dispersed in the mesoporous carbon support, resulting in spatial structural stability. The mesoporous carbon support obtained was highly graphitized and exhibited eminent electrical conductivity, which accelerated the electron transfer between the Fe3O4 nanoparticles by Fe(II)/Fe(III) redox cycles and m-GC by C = Csp2/C-Csp3 redox cycles, leading to the excellent peroxidase-mimetic activity of Fe3O4/m-GC. Km values for tetramethylbenzidine (TMB) and H2O2 were 26.8 and 15.8 times lower than that of natural horseradish peroxidase, respectively. Taking advantage of the peroxidase-mimetic activity of Fe3O4/m-GC, a colorimetric assay was fabricated for detecting glucose in the range 0.5 ~ 200 µM, with a limit of detection of 0.24 µM. Fig 1 A Schematic illustration of the preparation process of Fe3O4/m-GC, B schematic illustration of a proposed synergistic catalytic mechanism of TMB oxidation by Fe3O4/m-GC.

MicroRNA-20b suppresses the expression of ZFP-148 in viral myocarditis.

Viral myocarditis is a common cardiovascular disease, which seriously endangers the health of people and even leads to sudden unexpected death. MicroRNAs play very important roles in various physical and pathological processes including cardiogenesis and heart diseases. In recent years, miR-20b has been implicated in various diseases such as breast cancer, gastric cancer, hepatocellular carcinoma, cardiovascular diseases. However, the function of miR-20b in the pathological progress of viral myocarditis has not been reported. In this study, we found that miR-20b was up-regulated in mouse heart tissues post Coxsackievirus B3 (CVB3) infection. Bioinformatics analysis identified ZFP-148, a transcription factor that plays essential roles in the regulation of virus replication, is one of the predicted targets of miR-20b. MiR-20b expression was found to be up-regulated and ZFP-148 protein level was markedly repressed during viral myocarditis. Further studies demonstrated that miR-20b directly binds to the 3'-UTR of ZFP-148 and suppresses its translation. Moreover, aberrant expression of miR-20b promoted the expression of anti-apoptosis proteins Bcl-2 and Bcl-xL, suggesting that altered gene expression might promote cardiomyocytes survival in viral myocarditis. Our findings indicated that miR-20b might be a potential therapeutic target for CVB3-induced viral myocarditis and a useful marker for the diagnosis of viral myocarditis.

[Progress in Stress Cardiomyopathy and Its Forensic Application].

Stress cardiomyopathy is an atypical myocardial disease induced by emotional or physical stress, with the characteristic of left ventricular systolic dysfunction, transient imaging and electrocardiogram (ECG) changes. Sudden cardiac death can occur in severe cases. Clinical symptoms are likely to appear on acute myocardial infarction, but the exact pathological mechanism is unclear. In the present study, we perform a systematic review of the literature on the clinical manifestations, epidemiological characteristics, ECG, imaging and laboratory tests of stress cardiomyopathy, in order to provide the values for forensic pathology diagnosis.

The G-quadruplex ligand, SYUIQ-FM05, targets proto-oncogene c-kit transcription and induces apoptosis in K562 cells.

CONTEXT: N'-(7-Fluoro-5-N-methyl-10H-indolo[3,2-b]quinolin-5-ium)-N,N-dimethylpropane-1,3-diamine iodide (SYUIQ-FM05) is a semi-synthetic derivative of cryptolepine which is from Cryptolepis sanguinolenta (Lindl.) Schlechter (Periplocaeae). This ligand inhibits telomerase activity by stabilizing the G-quadruplex structure and induces growth arrest in cancer cells. OBJECTIVE: The anticancer activity of SYUIQ-FM05 via inhibiting c-kit transcription was investigated in leukemic cells. MATERIALS AND METHODS: The cytotoxicity of SYUIQ-FM05 in K562 cells was evaluated using a cell viability assay and flow cytometry (FCM) at 0.4, 2.0, 10.0 and 20.0 nM. Under the same concentrations of SYUIQ-FM05 or 100 nM imatinib mesylate (IM), quantitative polymerase chain reaction (Q-PCR) investigated transcription of c-kit and bcl-2, and western blotting analyzed the expression levels of c-Kit, total mitogen-activated protein kinase kinases (MEKs), phospho-MEK (p-MEK), total extracellular regulated protein kinases (ERKs), phospho-ERK (p-ERK), Bcl-2 and Bax. RESULTS: SYUIQ-FM05 inhibited cellular growth with an IC(50) of 10.83 ± 0.05 nM in K562 cells. c-Kit transcription was suppressed 2.69-, 4.39-, 7.71- and 10.52-fold at 0.4, 2.0, 10.0 and 20.0 nM SYUIQ-FM05, respectively, which produced proportional loss of total c-Kit protein except IM. Both SYUIQ-FM05 and IM downregulated p-MEK and p-ERK. Furthermore, bcl-2 transcription was suppressed 1.58- and 1.86-fold at 10.0 and 20.0 nM SYUIQ-FM05, respectively, but 0.4 and 2.0 nM SYUIQ-FM05 had no effect. A decrease in Bcl-2 and an increase in Bax appeared in these treated cells. DISCUSSION AND CONCLUSION: These findings demonstrate that SYUIQ-FM05 could induce apoptosis in a leukemic cell line through inhibiting c-kit transcription, which supports the anticancer potency of SYUIQ-FM05 in c-Kit-positive leukemic cells.

Efficacy of new hemostatic techniques in nonvariceal gastrointestinal bleeding: A systematic review and network meta-analysis.

OBJECTIVES: Nonvariceal gastrointestinal bleeding (NVGIB) is a common medical condition with significant mortality and morbidity. Several types of hemostatic modalities are currently available in clinical setting. This systematic review and network meta-analysis aimed to assess the efficacy of these modalities in treating NVGIB. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for studies that compared the efficacy of different hemostatic techniques (over-the-scope clip [OTSC], hemostatic powder [HP] and conventional endoscopic treatment [CET]) for NVGIB published up to June 2022. The 30-day rebleeding rate was regarded as the primary outcome. We performed pairwise and network meta-analyses for all treatments. The heterogeneity and transitivity were evaluated. RESULTS: Twenty-two studies were included. Regarding the 30-day rebleeding rate, OTSC and HP plus CET showed superior efficacy in treating NVGIB compared with CET (OTSC vs CET: relative risk [RR] 0.42, 95% confidence interval [CI] 0.28-0.60; HP plus CET vs CET: RR 0.40, 95% CI 0.17-0.87), while OTSC and HP plus CET had comparable efficacy (RR 0.95, 95% CI 0.38-2.31). HP plus CET ranked the highest in the network ranking estimate. The sensitivity analysis showed that it was not robust that OTSC was superior to CET regarding the short-term rebleeding rate and the initial hemostasis rate. While all-cause mortality, bleeding-related mortality and necessity of surgical or angiographic salvage therapy showed no statistically significant difference. CONCLUSION: OTSC and HP plus CET significantly reduced 30-day rebleeding rate compared to CET and had comparable efficacy in the treatment of NVGIB.

Imprudent blow, catastrophic consequence: a case of commotio cordis associated with violence.

Commotio cordis is a rare and catastrophic mechano-electric feedback syndrome, and it is especially apt to occur in male children, adolescents and youths during sports activities. The authors present a case of unexpected sudden death due to commotio cordis associated with violence. In a house of detention, a 19-year-old boy was punched and kicked in the face, neck and chest during a fight with another suspect in their ward. Unfortunately, his precordium was the major injured region. The victim turned pale, then lost the ability to resist and lost consciousness immediately. When the emergency medical personnel arrived, the victim was found in a condition of cardiac and respiratory arrest and he was pronounced dead at the scene without cardiopulmonary resuscitation. Both autopsy signs and forensic morphology were in accord with the criteria for commotio cordis diagnosis, showing no cardiac or other organic fatal lesions and no underlying cardiac diseases; moreover, the toxicological screening was negative for alcohol, drug and common toxicants. In the present case, the whole fight was seen by some witnesses in their ward, and it was recorded by the monitoring unit. Based on the statements of the witnesses and the monitoring videotape, combined with the forensic pathological and toxicological examinations, all the testimonies supported the conclusion that the cause of death was commotio cordis.

Metal Organic Frame-Upconverting Nanoparticle Assemblies for the FRET Based Sensor Detection of Bisphenol A in High-Salt Foods.

To resolve the occurrence of unfulfillable detection in high-salts foods, we used fluorescence resonant energy transfer (FRET) sensors based on nanoparticle upconversion. In this study, we developed a novel FRET sensor for the detection of bisphenol A (BPA) in high-salt foods. We based this approach on the assembly of aptamer modified upconversion nanoparticles (DNA1-UCNPs) and complementary DNA modified metal organic frames (DNA2-MOFs), which possessed corresponding wavelength absorption. Targeting BPA signal transduction was performed using the BPA aptamer, via competitive recognition between the BPA analyte and complementary DNA sequences in a high-salt solution. Sensor adaption in high-salt samples was attributed to functional hydrophilic groups, modified in the MOFs, and the enhanced colloidal stability of these MOFs. The MOF-UCNP assembly displayed considerable analytical performance in terms of BPA detection, with a linear range of 0.1-100 nM, and a limit of detection (LOD) of 0.02 nM, in a 340 mM NaCl food sample (the energy drink, Gatorade). Thus, this method provides a solid basis for small molecules detection in high-salt foods.

[Changes of RyR2 mRNA expression in rats suffering from acute myocardial ischemia].

OBJECTIVE: To investigate the changes of ryanodine receptor 2 (RyR2) mRNA expression in rats suffering from acute myocardial ischemia. METHODS: SD rats were divided randomly into normal control group, myocardial ischemia group and sudden death group. The models of myocardial ischemia and sudden cardiac death were induced by intraperitoneal injection of hypophysine. The changes of RyR2 mRNA expression in cardiac sarcoplasmic reticulum (SR) of rats suffering from myocardial ischemia were detected by fluorescent RT-PCR technique. RESULTS: The levels of RyR2 mRNA in the myocardial ischemia group and sudden death group were significant lower than those in the control group (P<0.05). CONCLUSION: Myocardial ischemia may induce down-regulation of cardiac SR RyR2 mRNA expression.

Determination of carbendazim in bananas by excitation-emission matrix fluorescence with three second-order calibration methods.

A novel method for determination of carbendazim in bananas is proposed in this study. After the bananas were simply extracted, the carbendazim was quantified under the interference of banana extract using the second-order calibration algorithms based on the parallel factor analysis (PARAFAC), the self-weighted alternating trilinear decomposition (SWATLD) and the alternating penalty trilinear decomposition algorithms (APTLD), respectively. For analysis of the complex samples, the so-called second-order advantage was adequately exploited and good results were obtained. Figures of merit, such as limit of detection, sensitivity and selectivity, were calculated to compare the performances of the three algorithms.

Determination of sulpiride in human urine using excitation-emission matrix fluorescence coupled with second-order calibration.

This paper proposes a new and effective approach for the quantitative analysis of sulpiride, a significant antipsychotic drug, in human urine samples by the incorporation of excitation-emission matrix (EEM) fluorescence and second-order calibration methodologies based on the alternating fitting residue (AFR) and self-weighted alternating trilinear decomposition (SWATLD) algorithms. With the application of a second-order advantage, the proposed strategy could be utilized for a direct concentration determination of sulpiride with a simple pretreatment step, even in the presence of serious natural fluorescent interferences. The average recoveries of sulpiride in complex urine samples by using AFR and SWATLD with an estimated component number of three were 101.2 +/- 2.1 and 94.4 +/- 0.7%, respectively. Moreover, the accuracy of the two algorithms was also evaluated through elliptical joint confidence region (EJCR) tests as well as the figures of merit, such as sensitivity (SEN), selectivity (SEL) and limit of detection (LOD). The experimental results demonstrated that both algorithms, as promising quantitative alternatives, have been satisfactorily applied to the determination of sulpiride in human urine, but the performance of AFR was slightly better than that of SWATLD.

[Expression of fibrillin-1 in congenital bicuspid aortic valves].

OBJECTIVE: To detect the expression of fibrillin-1 in congenital bicuspid aortic valves, and to investigate the molecular mechanism of congenital bicuspid aortic valves. METHODS: Specimens of aortic valve were obtained from 12 pediatric patients with congenital bicuspid aortic valve, 11 boys and 1 girl, aged 16.7 (10 - 18), including 5 cases of aortic stenosis (AS), 8 of aortic insufficiency (AI), and 1 of AS and AI, undergoing valve replacement, 8 children who died accidentally without cardiovascular system and collagen system diseases, 6 boys and 2 girls, aged 9.1 (1 - 17), collected in autopsy [normal (tricuspid) aortic valve controls], and 18 pediatric patients of rheumatic valvular heart disease with diseased tricuspid aortic valves who underwent aortic valve replacement, 13 boys and 5 girls, aged 16.5 (12 - 18) (rheumatic valvular heart disease controls). HE staining and light microscopy were conducted. Immunohistochemistry was used to detect the expression of fibrillin-1 in the aortic valves. RESULTS: Microscopy showed that the tissue structure of the congenital bicuspid aortic valves was unclear with hyperplasia of fibrous tissue. The grey degree value of fibrillin-1 of the congenital bicuspid aortic valve group was 170 +/- 10, significantly lower than those of normal aortic valve group and diseased tricuspid aortic valve group (126 +/- 8 and 73 +/- 16 respectively, both P < 0.05). There were not significant difference in the grey degree value of fibrillin-1 among the patients of congenital bicuspid aortic valves with AS, AI, and AS + AI (167 +/- 6, 171 +/- 8, and 168 +/- 6 respectively). CONCLUSION: The expression of fibrillin-1 is significantly reduced in congenital bicuspid aortic valves which may contribute to the morphological changes of the aortic valve leaflets and their resultant functional failure in congenital bicuspid aortic valves.

[Recent progress in epilepsy in neuropathology].

Epilepsy is a common cerebral disease, and may cause sudden death. Although electric activity study of epileptic brain had been emphasized in the past, the neuropathological study of epilepsy has become a main focus in clinical and forensic medicine recently. This article reviews the recent progress in neuropathology of epilepsy including developmental disorder, abnormal tumoral proliferation, hippocampal sclerosis, dual pathological alteration, and mossy fiber sprouting. Its significance in forensic medicine, particularly for the diagnosis of sudden unexpected death in epilepsy, is discussed.

Berberine containing quadruple therapy for initial Helicobacter pylori eradication: An open-label randomized phase IV trial.

BACKGROUND: Due to increasing antimicrobial resistance, a bismuth-based quadruple regimen has been recommended as an alternative first-line therapy for Helicobacter pylori (H pylori) eradication. However, different results are varied greatly and the availability of bismuth was limited in some countries. We assessed the efficacy and safety of 14-day berberine-containing quadruple therapy as an alternative regimen for H pylori eradication. METHODS: In a randomized, open-label, non-inferiority, phase IV trial between November 25, 2014, and October 15, 2015, 612 treatment-naive patients were randomly assigned to 14-day berberine-containing (n = 308) or 14-day bismuth-containing (n = 304) quadruple therapy. The primary outcomes were eradication rates determined by the C urea breath test (C-UBT) 28 days after the end of treatment. The secondary outcomes were adverse events and compliance. RESULTS: The baseline demographic data including age, gender, body mass index (BMI), general condition and severity score were not statistically different in both groups. The eradication rates in bismuth and berberine groups were 86.4% (266/308) and 90.1% (274/304) in intention-to-treat (ITT) analysis (P = .149), and 89.6% (266/297) and 91.3% (273/299) in per-protocol (PP) analysis (P = .470), respectively. No statistically significant difference was found in the overall incidence of adverse events between both groups (35.7% vs 28.6%, P = .060). CONCLUSIONS: Both regimens achieved the recommended efficacy for H pylori eradication. The berberine-containing quadruple regimen was not inferior to bismuth-containing quadruple regimen and can be recommended as an alternative regimen for H pylori eradication in the local region.

Glucocorticoid treatment inhibits intracerebral hemorrhage­induced inflammation by targeting the microRNA­155/SOCS­1 signaling pathway.

Intracerebral hemorrhage (ICH) results in inflammation, and glucocorticoids have been proven to be effective inhibitors of ICH­induced inflammation. However, the precise underlying mechanisms of ICH­induced inflammation and glucocorticoid function remain largely undefined. Using a mouse ICH model, the present study demonstrated that the short non­coding RNA molecule microRNA­155 (miR­155) is involved in the inflammatory process initiated by ICH in mice. Increased mRNA expression levels of miR­155, as well as the pro­inflammatory cytokines interferon­ß (IFN­ß), tumor necrosis factor­α (TNF­α) and interleukin­6 (IL­6), were observed in vivo following ICH. By contrast, the expression level of suppressor of cytokine signaling 1 (SOCS­1) protein was reduced in the ICH group compared with control mice. Similar results were observed in vitro using astrocytes, the primary effector cells in ICH. Compared with wild type astrocytes, astrocytes overexpressing miR­155 exhibited significant inhibition of SOCS­1 protein expression levels. These results suggest that miR­155 contributes to the development of ICH­induced inflammation in mice by downregulating SOCS­1 protein expression levels and promoting pro­inflammatory cytokine (IFN­ß, TNF­α and IL­6) production. Expression levels of miR­155 and pro­inflammatory cytokines in the ICH group were significantly decreased following dexamethasone administration. This suggests that glucocorticoids attenuate ICH­induced inflammation by targeting the miR­155/SOCS­1 signaling pathway in mice. In conclusion, the results of the present study demonstrated that the miR­155/SOCS­1 signaling pathway is required for ICH­induced inflammation, and glucocorticoids inhibit this process by targeting the miR­155/SOCS­1 signaling pathway.

[The research progress in Marfan syndrome].

Marfan syndrome (MFS) is a potentially fatal connective disorder that is inherited as an autosomal dominant trait with a prevalence of around 2-3 in 10000 live births. It is characterized by defects in the cardiovascular, skeletal and ocular systems. Evidence from genetic indicates that mutations in FBN1, the gene that encodes fibrillin-1 are responsible for MFS. In addition to skeletal, ocular, and cardiovascular feathers, patients with MFS have also involvement of skin, integument, lungs, and muscle tissue, and the condition in sudden death is also very common due to severe abnormalities of cardiovascular system.

[Expression of beta-amyloid precursor protein in diffuse axonal injury of rats].

OBJECTIVE: To explore an method for diffuse axonal injury (DAI) diagnosis and injury time estimation, the changes of beta-APP immunoreactivity and to observe the morphology of axonal in different parts of brain after experimental DAI injury. METHODS: The animal models of DAI was established according to the Marmarou's method. Immunohistochemistry and Gless staining were performed to observe the changes of beta-APP expression and the morphology of axon with the time elapsed after the DAI injury. RESULTS: In the brain injury group, the morphologic changes of axon in brain stem were showed as twisted, broken and swellen at 0.5 h, and the myelin sheaths broken could be observed, the retraction ball was found at 12 h. Those morphology changes further progressed at 12h, reached to peack up to 1 d, then repaired at 3 d, and recovered at 10 d; Meanwhile the analysis of beta-APP immunoreactivity was also showed a time-dependent difference as fellows: beta-APP expression begin at 3h, increased its immunoreactivity at 12h, reached to maximize at 1 d, decreased after 3 d, returned to basal level at 10 d. CONCLUSIONS: The results suggest that beta-APP immunohistochemistry combine with Gless staining be sensitive methods for DAI diagnosis, they could discover the time-dependent changes of the axonal morphology.The changes beta-APP are quite regular and could be used for timing DAI injury.

[Immunohistochemical and morphometrical study on the expression of interleukin-10 (IL-10) in different expressive parts during cutaneous wound healing in mice].

OBJECTIVE: To explore the expression of interleukin-10 (IL-10) in different expressive parts and its relationship with the wound age during cutaneous wound healing in mice. METHODS: Immunohistochemical and morphometrical analysis methods were performed on vital skin wounds. RESULTS: In normal and injury mouse skin IL-10 immunoreactivity was observed in epidermal cells. The expression of IL-10 in epidermal cells was already enhanced since 1-3h after incision, and it returned to lower lever by 24h, but increased again at 48h after injury. IL-10 immunoreactivive cells under epidermis were mainly infiltrating mononuclear cells. Morphometrically, the ratio of the number of infiltrating cells was evaluated. A subsequent increase in the IL-10 positive cells was observed in the granulation tissue beyond the wound and in dermal at 6h after incision, and the maximum ratio was (51.41 +/- 3.12)% in a 72h-old wound. Then the positive cells gradually decreased (29.38 +/- 2.64)%-(5.56 +/- 4.74)% after incision 96-168h. CONCLUSIONS: The expression characteristics of IL-10 in different expressive parts should be related to the wound age and morphometry of different expressive parts may be employed for determining the wound age.

[Adaptability assessment of economic and environmental development of Tangshan, Hebei, China].

It is vital to explore whether the economic system adapts to the environmental system as the relationship between economy and environment becomes a gradually concerned problem. Tangshan, a typical resource-based city, was chosen to study the adaptabilities and performances of economic developments in response to environmental changes from 1992 to 2011. It was found that the economic-environmental adaptation curve of Tangshan City had an overall fluctuating and increasing tendency. The systematic adaptability kept advancing, reflecting Tangshan paid much attention to environmental development in addition to economic performances, and the two aspects became more and more coordinated. Filtering analysis of the adaptive curve with Eviews software revealed that the potential systematic coordinating index was rising continuously, however, the sum of resilience gap for 20 years was still negative, which implied that fundamental contradictions between high economic development and high energy consumption and high pollutant emission still existed. Carrying out adaptive researches not only helps people to adapt to climate changes better, but also has significances for economic and environmental coordination and sustainability research.