Mechanism of Wenshen Xuanbi Decoction in the treatment of osteoarthritis based on network pharmacology and experimental verification.

To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.

A mechanistic model of calcium homeostasis leading to occurrence and propagation of secondary brain injury.

Secondary brain injury (SBI) refers to new or worsening brain insult after primary brain injury (PBI). Neurophysiological experiments show that calcium (Ca2+) is one of the major culprits that contribute to neuronal damage and death following PBI. However, mechanistic details about how alterations of Ca2+ levels contribute to SBI are not well characterized. In this paper, we first build a biophysical model for SBI related to calcium homeostasis (SBI-CH) to study the mechanistic details of PBI-induced disruption of CH, and how these disruptions affect the occurrence of SBI. Then, we construct a coupled SBI-CH model by formulating synaptic interactions to investigate how disruption of CH affects synaptic function and further promotes the propagation of SBI between neurons. Our model shows how the opening of voltage-gated calcium channels (VGCCs), decreasing of plasma membrane calcium pump (PMCA), and reversal of the Na+/Ca2+ exchanger (NCX) during and following PBI, could induce disruption of CH and further promote SBI. We also show that disruption of CH causes synaptic dysfunction, which further induces loss of excitatory-inhibitory balance in the system, and this might promote the propagation of SBI and cause neighboring tissue to be injured. Our findings offer a more comprehensive understanding of the complex interrelationship between CH and SBI.NEW & NOTEWORTHY We build a mechanistic model SBI-CH for calcium homeostasis (CH) to study how alterations of Ca2+ levels following PBI affect the occurrence and propagation of SBI. Specifically, we investigate how the opening of VGCCs, decreasing of PMCA, and reversal of NCX disrupt CH, and further induce the occurrence of SBI. We also present a coupled SBI-CH model to show how disrupted CH causes synaptic dysfunction, and further promotes the propagation of SBI between neurons.

Selective Photoaffinity Probe for Monitoring Farnesoid X Receptor Expression in Cultured Cells.

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is a vital ligand-activated transcriptional factor, which is highly expressed in the liver, intestine, and adrenal gland. However, FXR homeostasis is influenced by many factors, such as diet and circadian rhythm, and the expression of FXR differs in diverse organs. Currently, there is no method to monitor the FXR homeostasis in real time, which restricts us from further investigating the function of FXR under physiological and pathological conditions. In this project, classic FXR agonists were selected to be modified to targeting FXR. The photo-cross-linking diazirine group and alkynyl, a click reaction group, were incorporated to the ligands. Through biorthogonal reaction, fluorophore was linked to the ligands to realize the monitoring of FXR expression in cells.

Automatic Extraction of Power Lines from Aerial Images of Unmanned Aerial Vehicles.

Automatic power line extraction from aerial images of unmanned aerial vehicles is one of the key technologies of power line inspection. However, the faint power line targets and complex image backgrounds make the extraction of power lines a greater challenge. In this paper, a new power line extraction method is proposed, which has two innovative points. Innovation point one, based on the introduction of the Mask RCNN network algorithm, proposes a block extraction strategy to realize the preliminary extraction of power lines with the idea of "part first and then the whole". This strategy globally reduces the anchor frame size, increases the proportion of power lines in the feature map, and reduces the accuracy degradation caused by the original negative anchor frames being misclassified as positive anchor frames. Innovation point two, the proposed connected domain group fitting algorithm solves the problem of broken and mis-extracted power lines even after the initial extraction and solves the problem of incomplete extraction of power lines by background texture interference. Through experiments on 60 images covering different complex image backgrounds, the performance of the proposed method far exceeds that of commonly used methods such as LSD, Yolact++, and Mask RCNN. DSCPL, TPR, precision, and accuracy are as high as 73.95, 81.75, 69.28, and 99.15, respectively, while FDR is only 30.72. The experimental results show that the proposed algorithm has good performance and can accomplish the task of power line extraction under complex image backgrounds. The algorithm in this paper solves the main problems of power line extraction and proves the feasibility of the algorithm in other scenarios. In the future, the dataset will be expanded to improve the performance of the algorithm in different scenarios.

A model of metabolic supply-demand mismatch leading to secondary brain injury.

Secondary brain injury (SBI) is defined as new or worsening injury to the brain after an initial neurologic insult, such as hemorrhage, trauma, ischemic stroke, or infection. It is a common and potentially preventable complication following many types of primary brain injury (PBI). However, mechanistic details about how PBI leads to additional brain injury and evolves into SBI are poorly characterized. In this work, we propose a mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH) of SBI. Our model, based on the Hodgkin-Huxley model, supplemented with additional dynamics for extracellular potassium, oxygen concentration, and excitotoxity, provides a high-level unified explanation for why patients with acute brain injury frequently develop SBI. We investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, and seizures can induce SBI and suggest three underlying paths for how events following PBI may lead to SBI. The proposed model also helps explain several important empirical observations, including the common association of acute brain injury with seizures, the association of seizures with tissue hypoxia and so on. In contrast to current practices which assume that ischemia plays the predominant role in SBI, our model suggests that metabolic crisis involved in SBI can also be nonischemic. Our findings offer a more comprehensive understanding of the complex interrelationship among potassium, oxygen, excitotoxicity, seizures, and SBI.NEW & NOTEWORTHY We present a novel mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH), which attempts to explain why patients with acute brain injury frequently develop seizure activity and secondary brain injury (SBI). Specifically, we investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, seizures, all common sequalae of primary brain injury (PBI), can induce SBI and suggest three underlying paths for how events following PBI may lead to SBI.

[Effects of electroacupuncture with different courses on the synaptic structure and synaptic function-related proteins in mice with radiation-induced brain injury].

The aim of the present study was to investigate the effects of different courses of electroacupuncture on synaptic structure and synaptic function-related proteins expression in the hippocampal CA1 region of radiation-induced brain injury mice. Sixty C57BL/6J male mice were randomly divided into control group, radiation-induced brain injury model group, 1-week electroacupuncture group (EA1), 2-week electroacupuncture group (EA2), 3-week electroacupuncture group (EA3), and electroacupuncture-control (EA-Ctrl) group. The mice in model group were exposed to X-ray irradiation (8 Gy, 10 min) to establish radiation-induced brain injury model. The mice in EA groups were acupunctured at electroacupuncture points (Baihui, Fengfu and bilateral Shenshu) for 1 week, 2 weeks and 3 weeks respectively after radiation. Immunohistochemistry was used to observe synaptic structure in hippocampal CA1 region. The expressions of brain-derived neurotrophic factor (BDNF), synapsin-1 and postsynaptic density 95 (PSD95) in the hippocampal CA1 region of each group were detected by RT-PCR and Western blotting. The results showed that the nuclear gap in model and EA-Ctrl groups was significantly decreased compared to control group, however nucleus to cytoplasm ratio was significantly increased. The synaptic cleft, postsynaptic density (PSD) thickness, the mitochondrial surface density, volume density and specific surface area were significantly reduced. Compared with model group, the nucleus to cytoplasm ratio of EA2 group was significantly decreased, the PSD thickness and mitochondrial volume density were significantly increased; the nuclear gap of EA3 group was significantly increased, nucleus to cytoplasm ratio was significantly decreased, synaptic cleft and PSD thickness were significantly increased, and the mitochondrial surface density and specific surface area were all increased significantly. In addition, compared with the control group, the gene and protein expressions of BDNF, synapsin-1 and PSD95 in the hippocampal CA1 region of the model group and EA-Ctrl group were significantly decreased. However, compared with the model group, the gene expression of synapsin-1 in EA groups was significantly up-regulated, the gene expression of BDNF in EA1 and EA2 groups was significantly up-regulated, and the gene expression of PSD95 in EA2 group was significantly up-regulated. Moreover, the protein expressions of BDNF, synapsin-1 and PSD95 of EA groups were significantly up-regulated compared with the model group. These results indicate that the synaptic structure and the expression of synaptic function-related proteins in hippocampal CA1 region were injured by radiation exposure, whereas electroacupuncture intervention can significantly improve the synaptic structure and function damage caused by radiation.

A high-density genetic map and QTL mapping of leaf traits and glucosinolates in Barbarea vulgaris.

BACKGROUND: Barbarea vulgaris is a wild cruciferous plant and include two distinct types: the G- and P-types named after their glabrous and pubescent leaves, respectively. The types differ significantly in resistance to a range of insects and diseases as well as glucosinolates and other chemical defenses. A high-density linkage map was needed for further progress to be made in the molecular research of this plant. RESULTS: We performed restriction site-associated DNA sequencing (RAD-Seq) on an F2 population generated from G- and P-type B. vulgaris. A total of 1545 SNP markers were mapped and ordered in eight linkage groups, which represents the highest density linkage map to date for the crucifer tribe Cardamineae. A total of 722 previously published genome contigs (50.2 Mb, 30% of the total length) can be anchored to this high density genetic map, an improvement compared to a previously published map (431 anchored contigs, 38.7 Mb, 23% of the assembly genome). Most of these (572 contigs, 31.2 Mb) were newly anchored to the map, representing a significant improvement. On the basis of the present high-density genetic map, 37 QTL were detected for eleven traits, each QTL explaining 2.9-71.3% of the phenotype variation. QTL of glucosinolates, leaf size and color traits were in most cases overlapping, possibly implying a functional connection. CONCLUSIONS: This high-density linkage map and the QTL obtained in this study will be useful for further understanding of the genetic of the B. vulgaris and molecular basis of these traits, many of which are shared in the related crop watercress.

Hemodynamic effects of myocardial bridging in patients with hypertrophic cardiomyopathy.

Myocardial bridging (MB) is linked to angina and myocardial ischemia and may lead to sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, it remains unclear how MB affect the coronary blood flow in HCM patients. The aim of this study was to assess the effects of MB on coronary hemodynamics in HCM patients. Fifteen patients with MB (7 HCM and 8 non-HCM controls) in their left anterior descending (LAD) coronary artery were chosen. Transient computational fluid dynamics (CFD) simulations were conducted in anatomically realistic models of diseased (with MB) and virtually healthy (without MB) LAD from these patients, reconstructed from biplane angiograms. Our CFD simulation results demonstrated that dynamic compression of MB led to diastolic flow disturbances and could significantly reduce the coronary flow in HCM patients as compared with non-HCM group (P < 0.01). The pressure drop coefficient was remarkably higher (P < 0.05) in HCM patients. The flow rate change is strongly correlated with both upstream Reynolds number and MB compression ratio, while the MB length has less impact on coronary flow. The hemodynamic results and clinical outcomes revealed that HCM patients with an MB compression ratio higher than 65% required a surgical intervention. In conclusion, the transient MB compression can significantly alter the diastolic flow pattern and wall shear stress distribution in HCM patients. HCM patients with severe MB may need a surgical intervention.NEW & NOTEWORTHY In this study, the hemodynamic significance of myocardial bridging (MB) in patients with hypertrophic cardiomyopathy (HCM) was investigated to provide valuable information for surgical decision-making. Our results illustrated that the transient MB compression led to complex flow patterns, which can significantly alter the diastolic flow and wall shear stress distribution. The hemodynamic results and clinical outcomes demonstrated that patients with HCM and an MB compression ratio higher than 65% required a surgical intervention.

miR-486-5p Inhibits Inflammatory Response, Matrix Degradation and Apoptosis of Nucleus Pulposus Cells through Directly Targeting FOXO1 in Intervertebral Disc Degeneration.

BACKGROUND/AIMS: microRNA-486-5p (miR-486-5p) and forkhead box protein O1 (FOXO1) play an important role in the development of intervertebral disc degeneration (IDD). However, their molecular mechanisms in IDD remain unknown. METHODS: qRT-PCR assay was used to identify miR-486-5p expression in nucleus pulposus (NP) cells. In-vitro transfection, CCK-8, flow cytometry and luciferase reporter assay were used to validate the role and relationship of miR-486-5p and FOXO1 in lipopolysaccharides (LPS)-stimulated NP cells. qRT-PCR and Western blot were used to measure the expression levels of inflammatory cytokines, matrix degrading enzymes, and extracellular matrix (ECM)-related genes. RESULTS: miR-486-5p expression was significantly down-regulated, while FOXO1 expression was up-regulated in LPS-treated NP cells (P<0.001). miR-486-5p over-expression repressed LPS-induced expressions of inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and matrix degrading enzymes (MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5), and promoted the expressions of LPS-inhibited ECM-related genes (Aggrecan and Collagen II) (all P<0.001). In addition, miR-486-5p over-expression protected NP cells against LPS-induced apoptosis. However, inhibition of miR-486-5p led to the opposite effects. Mechanically, FOXO1 was a direct target gene of miR-486-5p. Over-expressed FOXO1 aggravated LPS-induced injury, and antagonized protection effects of miR-486-5p. CONCLUSION: miR-486-5p can inhibit inflammatory response, ECM degradation and apoptosis in NP cells by directly targeting FOXO1, which may contribute to the biological therapy of IDD.

A novel neural computational model of generalized periodic discharges in acute hepatic encephalopathy.

Acute hepatic encephalopathy (AHE) due to acute liver failure is a common form of delirium, a state of confusion, impaired attention, and decreased arousal. The electroencephalogram (EEG) in AHE often exhibits a striking abnormal pattern of brain activity, which epileptiform discharges repeat in a regular repeating pattern. This pattern is known as generalized periodic discharges, or triphasic-waves (TPWs). While much is known about the neurophysiological mechanisms underlying AHE, how these mechanisms relate to TPWs is poorly understood. In order to develop hypotheses how TPWs arise, our work builds a computational model of AHE (AHE-CM), based on three modifications of the well-studied Liley model which emulate mechanisms believed central to brain dysfunction in AHE: increased neuronal excitability, impaired synaptic transmission, and enhanced postsynaptic inhibition. To relate our AHE-CM to clinical EEG data from patients with AHE, we design a model parameter optimization method based on particle filtering (PF-POM). Based on results from 7 AHE patients, we find that the proposed AHE-CM not only performs well in reproducing important aspects of the EEG, namely the periodicity of triphasic waves (TPWs), but is also helpful in suggesting mechanisms underlying variation in EEG patterns seen in AHE. In particular, our model helps explain what conditions lead to increased frequency of TPWs. In this way, our model represents a starting point for exploring the underlying mechanisms of brain dynamics in delirium by relating microscopic mechanisms to EEG patterns.

Rhabdothermincola sediminis gen. nov., sp. nov., a new actinobacterium isolated from hot spring sediment, and emended description of the family Iamiaceae.

One thermophilic bacterium, designated strain SYSU G02662T, was isolated from hot spring sediment sampled in Tibet, PR China. Polyphasic taxonomic analyses and whole-genome sequencing were used to determine the taxonomy position of the strain. Phylogenetic analysis using 16S rRNA gene sequences indicated that strain SYSU G02662T showed the highest sequence similarity to Actinomarinicola tropica SCSIO 58843T (95.1 %). The strain could be differentiated from other species of the family Iamiaceae by its distinct phenotypic and genotypic characteristics. Cells of strain SYSU G02662T were aerobic, Gram-staining-positive and short rodshaped. Growth occurred optimally at 45 °C and pH 7.0. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The respiratory quinone was MK-9 (H8), while the major fatty acids (>10 %) were C16 : 0, C17 : 0, C18 : 0 and iso-C16 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. The G+C content of the genomic DNA was 70.5 % based on the draft genomic sequence. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU G02662T represents a novel species of a novel genus in the family Iamiaceae, for which the name Rhabdothermincola sediminis gen. nov., sp. nov. is proposed. The type strain of the proposed novel species is SYSU G02662T (=CGMCC 4.7688T=KCTC 49500T).

Outcome and Pathological Characteristics of Primary Malignant Cardiac Tumors.

The literature on malignant cardiac tumors is relatively limited because they are rare, especially among the Chinese population. We analyzed 14 patients diagnosed with malignant cardiac tumors in Fuwai Hospital and present the results of surgical treatments on the tumors. The mean age at tumor diagnosis was 47 years in a male-dominated cohort. There was a high frequency of pericardial effusion and coronary artery involvement in our group. We compared the survival times of patients who received different treatments and found that surgery improved prognosis of tumors, especially for patients who underwent orthotopic heart transplantation.

[Effects of different concentrations of calcitonin gene-related peptide on long-term depression of hippocampus in mice].

The purpose of this study was to explore the effects of calcitonin gene-related peptide (CGRP) on the long-term depression (LTD) of hippocampus in mice. Sixty C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP (50, 100, and 200 nmol/L) groups, CGRP + CGRP8-37 group and CGRP + APV group (10 mice for each group). The effects of exogenous application of different concentrations of CGRP on synaptic plasticity and LTD in hippocampus of mice were detected by in vitro recording of local field potential. The results showed that higher doses (100 and 200 nmol/L) of CGRP significantly enhanced the induction of LTD in the hippocampus. Moreover, CGRP increased the magnitude of N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents. The above-mentioned effects of CGRP were blocked by either CGRP selective antagonist CGRP8-37 or NMDA receptor antagonist APV. These results suggest that CGRP can dose-dependently enhance the induction of LTD in hippocampus of mice, and the underlying mechanism involves the mediation of NMDA receptor function.

[Effects and mechanisms of electro-acupuncture on proliferation and differentiation of neural stem cells in C57 mice exposed to different doses of X-ray radiation].

The present study was aimed to investigate the effects and mechanisms of electro-acupuncture (EA) on proliferation and differentiation of neural stem cells in the hippocampus of C57 mice exposed to different doses of X-ray radiation. Thirty-day-old C57BL/6J mice were randomly divided into control, irradiation, and EA groups. The control group was not treated with irradiation. The irradiation groups were exposed to different doses of X-ray (4, 8 or 16 Gy) for 10 min. The EA groups were electro-acupunctured at Baihui, Fengfu and bilateral Shenyu for 3 courses of treatment after X-ray radiation. Immunohistochemistry was used to evaluate proliferation and differentiation of the hippocampal neural stem cell. RT-PCR and Western blot were used to detect mRNA and protein expressions of Notch1 and Mash1 in the hippocampus, respectively. The results showed that, compared with the control group, the numbers of BrdU positive cells (4, 8 Gy subgroup) and BrdU/NeuN double-labeling positive cells (3 dose subgroups) were decreased significantly in the irradiation group, but the above changes could be reversed by EA. Compared with the control group, the number of BrdU/GFAP double-labeling positive cells in each dose subgroup of irradiation group was decreased significantly, while EA could reverse the change of 4 and 8 Gy dose subgroups. In addition, compared with the control group, the expression levels of Notch1 mRNA and protein in hippocampus were up-regulated, and the expression levels of Mash1 mRNA and protein were significantly decreased in each dose subgroup of irradiation group. Compared with irradiation group, the expression levels of Notch1 mRNA and protein in hippocampus of EA group were decreased significantly in each dose subgroup, and the expression levels of Mash1 mRNA and protein were increased significantly in 4 and 8 Gy subgroups. These results suggest that irradiation affects the proliferation and differentiation of neural stem cells in hippocampus of mice, whereas EA may significantly increase the proliferation and differentiation of hippocampal neural stem cells via the regulation of Notch signaling pathway.

[Current situation and consideration of patent protection in classical representative famous prescriptions in China].

Classical Representative Famous Prescription is the valuable cultural heritage of Chinese medicine. In November 2018,the State Council issued the " Intensive Implementation of the National Intellectual Property Strategy in 2018 to Accelerate the Construction of IP Strong Country",explicitly proposing to strengthen the intellectual property protection of Classical Representative Famous Prescription.How about the current situation of intellectual property protection of lassical Representative Famous Prescription in China? We selected Liuwei Dihuang Pills,Shengmai Powder and Guizhi Fuling Pills( three representative drugs on market) from Chinese Pharmacopoeia2015 Volume I issued by Chinese Pharmacopoeia Commission to analyze their patent layout,reflecting its status quo of patent protection as follows: first,in recent years,the number of related patent applications for Classical Representative Famous Prescriptions has declined,which was positively correlated with the drug registration and approval policies in recent years,but the policy dividend has not been reflected in the patent application,which may be related to the long period of pharmaceutical R&D; secondly,the patent applicant in the field of Chinese medicine is mainly based on individuals,but the applicant of Classical Representative Famous Prescription is mainly of enterprises,and in addition,the company applicants have the highest authorization rate; thirdly,the main technologies are to improve preparation method and the dosage form in the research and development of Classical Representative Famous Prescription,but these two types of authorized patents have much difficulty in further application on the market. Therefore,the innovative entities shall look for a new breakthrough in secondary development and utilization of Classical Representative Famous Prescriptions.

A modified method for isolation of human cardiomyocytes to model cardiac diseases.

BACKGROUND: Cardiomyocytes derived from animals and induced pluripotent stem cells (iPSCs) are two main cellular models to study cardiovascular diseases, however, neither provides precise modeling of the response of mature human cardiomyocytes to disease or stress conditions. Therefore, there are emerging needs for finding an optimized primary human cardiomyocytes isolation method to provide a bona fide cellular model. METHODS AND RESULTS: Previous established protocols for the isolation of primary human cardiomyocytes are limited in their application due to relatively low cell yield and the requirement of tissue integrity. Here, we developed a novel, simplified method to isolate human cardiomyocytes robustly with improved viability from tissue slicing. Isolated cardiomyocytes showed intact morphology, retained contractility, ion flux, calcium handling, and responses to neurohormonal stimulation. In addition, we assessed the metabolic status of cardiomyocytes from different health conditions. CONCLUSION: We present a novel, simplified method for isolation of viable cardiomyocytes from human tissue.

Serotonin Transporter Gene (SLC6A4) Polymorphism May Be Associated with Chinese Globus Pharyngeus and Its Antidepressant Effects.

BACKGROUND: Although globus pharyngeus is not rare in clinical practice, little is known about its associated gene polymorphism. We investigated the association between the SLC6A4 polymorphism and globus pharyngeus and its response to treatment with antidepressants. METHODS: A total of 84 patients were diagnosed with globus pharyngeus according to Rome III, and 160 healthy controls were genotyped for the SLC6A4 polymorphism using polymerase chain reaction amplification and agarose gel electrophoresis. All patients with globus were studied using high-resolution manometry pre-therapy. Globus patients were randomized into paroxetine or amitriptyline groups for a 6-week treatment and asked to complete the following pre- and post-therapy questionnaires: the Glasgow Edinburgh Throat Scale (GETS), the Pittsburgh Sleep Quality Index, and the Hamilton Rating Scale Anxiety/Depression. Treatment response was defined as a >50% reduction in the GETS scores. RESULTS: A significant difference was observed in the globus S/S genotype with anxiety compared to that without anxiety (χ2 = 14.579, p = 0.006). The L/S genotype showed a significant difference between high upper esophageal sphincter pressure (>104 mm Hg) and non-high upper esophageal sphincter pressure patients (χ2 = 14.433, p = 0.006). A significant association between the S/S genotype and the response to antidepressant treatment was also observed, while patients with sleep disorders or depression showed no association. CONCLUSION: A significant association was observed between the S/S genotype of the SLC6A4 polymorphism and globus pharyngeus, suggesting that SLC6A4 is a potential candidate gene involved in the pathogenesis of globus pharyngeus.

An in vitro Experimental Insight into the Osteoblast Responses to Vitamin D3 and Its Metabolites.

BACKGROUND: 25-hydroxyvitamin D3 (25[OH]VD3) has recently been found to be an active hormone. Its biological actions are also demonstrated in various cell types. However, the precise influences of vitamin D3 (VD3) and its metabolites (25[OH]VD3, 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2VD3]) on the osteoblast differentiation remain largely unknown. In this work, we investigated the effects of VD3 and its metabolites in different concentrations on the early and later osteoblast differentiation and biomineralization. METHODS: We first used quantitative real-time polymerase chain reaction (RT-qPCR) to evaluate the responsiveness of osteoblasts to VD3, 25(OH)VD3 or 1α,25-(OH)2VD3. We also evaluated the proliferation, differentiation and biomineralization of osteoblast at different time points via cell counting kit-8 assay and the analysis of osteogenic markers. RESULTS: The experimental results confirmed that osteoblasts could be responsive to 25(OH)VD3 and 1α,25-(OH)2VD3 but could not directly metabolize VD3 and 25(OH)VD3. Only 200 nmol/L VD3 significantly promoted osteoblast proliferation, while 25(OH)VD3 and 1α,25-(OH)2VD3 did not show obvious actions. Moreover, the early osteogenic markers were increased by 25(OH)VD3 and 1α,25-(OH)2VD3 in a dose-dependent manner. More importantly, only 25(OH)VD3 had accelerated the gene and protein expressions of osteocalcin and the biomineralization level of osteoblasts. CONCLUSIONS: Our findings provide reliable evidence that 25(OH)VD3 at 100-200 nmol/L can induce the early and later osteoblast differentiation and biomineralization for clinical bone tissue engineering.

Study on a New Ultraviolet Sterilizer to the Surface Disinfection of the Ultrasound Probe.

We studied the disinfection effect of a new ultraviolet (UV) sterilizer and its utilization on ultrasound probe surfaces. Carrier quantitative germicidal tests, simulated on-the-spot trials, and organic substance influence tests were used to carry out experimental observation. Artificially infected probes were disinfected using the sterilizer or a germicidal lamp for comparison. The total number and types of bacteria were determined and identified. Our results demonstrated the sterilizer had the best disinfection effect among three different disinfection methods in hospital. The sterilizer has been used in a hospital setting for 2 years with no notable damage to the ultrasound probe instrument. It has the advantages of fast disinfection, high disinfection effect, and good compatibility with the ultrasound instrument, worthy of being a promoted application in medical institutions.

[Effect of different concentrations of calcitonin gene-related peptide on the long-term potentiation in hippocampus of mice].

The purpose of this study was to explore the effects of different concentrations of calcitonin gene-related peptide (CGRP) on long-term potentiation (LTP) in the hippocampus of mice. C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP groups, and CGRP + CGRP8-37 group (10 mice for each group). Different concentrations of CGRP (50, 100 and 200 nmol/L) were given to the hippocampal slices of mice. The presynaptic release of neurotransmitters and the induction of LTP were measured by extracellular field recording techniques. The result showed that different concentrations of CGRP did not affect the presynaptic release of neurotransmitters, but 100 and 200 nmol/L CGRP increased the amplitude of LTP induced in the hippocampus of mice. This facilitation effect of CGRP was blocked by its specific antagonist CGRP8-37. These results suggest that CGRP dose-dependently facilitates the induction of LTP in the hippocampus of mice through its specific receptor.