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Objective: We have previously reported that interleukin-1β (IL-1β) up-regulates the expression of Wnt-5A and the activation of Wnt-5A signaling induces matrix metalloproteinase (MMP) through the c-Jun N-terminal kinase pathway in condylar chondrocytes (CCs) of the temporomandibular joint (TMJ). These results suggest that Wnt-5A could play an essential role in IL-1β-mediated cartilage destruction. The objective of this study was to investigate the molecular mechanism underlying IL-1β-induced up-regulation of Wnt-5A in TMJ CCs. Methods: Primary CCs, limb chondrocytes (LCs) and SW1353 human chondrosarcoma cells were treated with IL-1β in the presence or absent of BAY 11-7082 (an inhibitor of IκBα-phosphorylation). Then, expression of Wnt-5A was estimated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunocytofluorescence. Transient transfection of p65 expression vector and chromatin immunoprecipitation (ChIP) assay was performed to define the effect of p65 on Wnt-5A expression. Results: IL-1β up-regulated Wnt-5A expression at both the RNA and protein levels in articular chondrocytes. The inhibitor of IκBα-phosphorylation, BAY 11-7082, blocked the induction of Wnt-5A by IL-1β in a dose-dependent manner. Moreover, experiments with overexpression of p65 and ChIP established that induction of Wnt-5A by IL-1β is mediated through the NF-κB pathway, especially the p65 subunit. Conclusion: These results clarify the molecular mechanism underlying up-regulation of Wnt-5A by IL-1β in chondrocytes, suggesting an important functional crosstalk between Wnt-5A and NF-κB signaling pathways. This finding provides new insights into the involvement of Wnt signaling in the cartilage destruction caused by arthritis. [ABSTRACT FROM AUTHOR]

Can the transcriptomic profile of a neuron predict its physiological properties? Using a Patch-seq dataset of the primary visual cortex, we addressed this question by focusing on spike rate adaptation (SRA), a well-known phenomenon that depends on small conductance calcium (Ca)-dependent potassium (SK) channels. We first show that in parvalbumin-expressing (PV) and somatostatin-expressing (SST) interneurons (INs), expression levels of genes encoding the ion channels underlying action potential generation are correlated with the half-width (HW) of spikes. Surprisingly, the SK encoding gene is not correlated with the degree of SRA (dAdap). Instead, genes that encode proteins upstream from the SK current are correlated with dAdap, a finding validated by a different dataset from the mouse's primary motor cortex that includes pyramidal cells and interneurons, as well as physiological datasets from multiple regions of macaque monkeys. Finally, we construct a minimal model to reproduce observed heterogeneity across cells, with testable predictions.

WOX11/12 is a homeobox gene of WOX11 and WOX12 in Arabidopsis that plays important roles in crown root development and growth. It has been reported that WOX11/12 participates in adventitious root (AR) formation and different abiotic stress responses, but the downstream regulatory network of WOX11/12 in poplar remains to be further investigated. In this study, we found that PagWOX11/12a is strongly induced by PEG-simulated drought stress. PagWOX11/12a-overexpressing poplar plantlets showed lower oxidative damage levels, greater antioxidant enzyme activities and reactive oxygen species (ROS) scavenging capacity than non-transgenic poplar plants, whereas PagWOX11/12a dominant repression weakened root biomass accumulation and drought tolerance in poplar. RNA-seq analysis revealed that several differentially expressed genes (DEGs) regulated by PagWOX11/12a are involved in redox metabolism and drought stress response. We used RT-qPCR and yeast one-hybrid (Y1H) assays to validate the downstream target genes of PagWOX11/12a. These results provide new insights into the biological function and molecular regulatory mechanism of WOX11/12 in the abiotic resistance processes of poplar., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Bony changes such as glenoid bone defects and Hill-Sachs lesions are responsible for recurrent anterior shoulder dislocations. With the development of arthroscopic techniques as well as arthroscopic surgical instruments, arthroscopic repair of bony structures has become an important surgical procedure for the treatment of recurrent shoulder dislocation. In this Technical Note, we used screws to fill Hill-Sachs lesions and autologous iliac bone grafts combined with soft tissue to repair the glenoid bone defects. In the surgical procedures within the shoulder, all operations are done arthroscopically, are minimally invasive, and achieve the goal of repairing composite shoulder injuries., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by the 10.13039/501100001809National Natural Science Foundation of China (No. 81672225, 81601941); the National Clinical Research Center for Geriatric Disorders, 10.13039/501100011790Xiangya Hospital, Central South University (2021KFJJ06); and Hunan Provincial Natural Foundation of China (2021JJ30040). All authors (Y-M.W., Y-F.X., J-H.M., Y-L.X., H.T., S-G.G.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus . Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro , the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Agaricus blazei is a rare medicinal and edible fungus with a crispy taste and delicious flavor. Both fruiting body and mycelium are rich in polysaccharides, sterols, terpenoids, peptides, lipids, polyphenols, and other active ingredients, which have strong pharmacological activities such as anti-tumor, lipid-lowering, glucose-lowering, immunomodulation, optimization of intestinal flora, and anti-oxidation. Therefore, it is a kind of fungal resource with a great prospect of edible and medicinal development. Among the reported chemical components of A. blazei, blazeispirol is a series of sterol compounds unique to A. blazei, which has a spiral structure and is different from classical steroids. It is an important active ingredient found in the mycelium of A. blazei and has significant hepatoprotective activity. It can be used as a phylogenetic and chemotaxonomic marker of A. blazei strains and is considered an excellent lead compound for drug development. According to the skeleton structure characteristics, the 17 discovered blazeispirol compounds can be divided into two types: blazeispirane and problazeispirane. In order to further explore the resource of blazeispirol compounds of A. blazei, the discovery, isolation, structure, biological activity, and biosynthetic pathways of blazeispirol compounds of A. blazei were systematically reviewed. Besides, the metabolic regulation strategies related to the fermentation synthesis of blazeispirol A by A. blazei were discussed. This review could provide a reference for the efficient synthesis and development of blazeispirol compounds, the research and development of related drugs and functional foods, and the quality improvement of A. blazei and other medicinal and edible fungi resources and derivatives.

The purpose of this study was to reveal the current trends and preferences of Chinese orthopedic surgeons regarding anterior cruciate ligament (ACL) reconstruction through a nationwide web-based survey conducted in China. The survey questionnaire was distributed via WeChat to the chairmen of provincial orthopedic and sports medicine organizing committees in China, who then shared it in their respective WeChat workgroups. The questionnaire consisted of 52 multiple-choice questions covering 8 sections. Data collection was implemented by Questionnaire Star. A total of 812 valid questionnaires were returned: 94.21% of the respondents preferred single-bundle reconstruction of ACL, while 61.70% preferred autogenous semitendinosus plus gracilis reconstruction; 76.35% of the respondents preferred establishing the femoral tunnel first, while 47.29% preferred establishing the femoral tunnel through a medial auxiliary approach; and 85.10% of the respondents recommended patients to undergo surgery within 3 months after ligament injury. Besides, the vast majority of respondents chose to retain the ligamentous remnant bundle (92.98%) and recommended routine use of knee braces postoperatively (94.09%). It is recommended to perform arthroscopic single-bundle ACL reconstruction with the remnant preserving technique using a hamstring autograft within 3 months of ACL rupture, with support of postoperative functional braces., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Arthroscopic repair of Bankart injury is the first choice for the treatment of anterior shoulder instability. How to avoid recurring shoulder joint dislocation is a challenge, especially when combined with Hill-Sachs lesions. The arthroscopy technology allows for broader vision and less surgical trauma but is limited by a smaller operating space. At present, extensive descriptions about the surgical procedure of arthroscopic Bankart repair have been published. In this Technical Note, we describe the use of remplissage filling with Hill-Sachs lesion combined with Bankart repair to further improve the surgical accuracy and clinical efficacy. In particular, the application of single needle-assisted outside-in remplissage technique and Bankart repair is introduced in detail., Competing Interests: The authors report the following potential conflicts of interest or sources of funding: This work was supported by the 10.13039/501100001809National Natural Science Foundation of China (No. 81672225, 81601941), the National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 10.13039/501100002822Central South University (2021KFJJ06), and Hunan Provincial Natural Foundation of China (2021JJ30040). All authors (Y.-M.W., Y.-F.X., H.T., Y.-L.X., W.-J.L., J.-H.M., S.-G.G.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2024 The Authors.)

Massive rotator cuff tears are a huge challenge for orthopaedic surgeons, as the patients may be in need of multiple operations, even including reverse total shoulder arthroplasty. The various repair methods for the rotator cuff, such as partial rotator cuff repair, patch-augmented rotator cuff repair, bridging rotator cuff reconstruction with graft interposition, tendon transfer, and superior capsular reconstruction, have always been the focus of research. During surgical intervention for failed rotator cuff repairs, complexity of tears, poor tissue quality, retained hardware, and adhesions are the problems routinely encountered. In this Technical Note, we describe the technique of interposition grafting using fascia lata autograft to reconstruct the rotator cuff after failed primary repair., (© 2023 The Authors.)

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda . This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Ma, Long, Yan, Peng, Cai, Zhong, Huang, Qiao, Zhou, Cai, Cheng, Zhou, Han, Liu, Zhang, Tang, Meng and Luo.)

Cortical GABAergic interneurons (INs) represent a diverse population of mainly locally projecting cells that provide specialized forms of inhibition to pyramidal neurons and other INs. Most recent work on INs has focused on subtypes distinguished by expression of Parvalbumin (PV), Somatostatin (SST), or Vasoactive Intestinal Peptide (VIP). However, a fourth group that includes neurogliaform cells (NGFCs) has been less well characterized due to a lack of genetic tools. Here, we show that these INs can be accessed experimentally using intersectional genetics with the gene Id2 . We find that outside of layer 1 (L1), the majority of Id2 INs are NGFCs that express high levels of neuropeptide Y (NPY) and exhibit a late-spiking firing pattern, with extensive local connectivity. While much sparser, non-NGFC Id2 INs had more variable properties, with most cells corresponding to a diverse group of INs that strongly expresses the neuropeptide CCK. In vivo, using silicon probe recordings, we observed several distinguishing aspects of NGFC activity, including a strong rebound in activity immediately following the cortical down state during NREM sleep. Our study provides insights into IN diversity and NGFC distribution and properties, and outlines an intersectional genetics approach for further study of this underappreciated group of INs., Competing Interests: RM, SD, MV, HZ, IK, JM, JH, YH, BS, GB, BR No competing interests declared, (© 2023, Machold et al.)

Neocortical layer 1 (L1) consists of the distal dendrites of pyramidal cells and GABAergic interneurons (INs) and receives extensive long-range "top-down" projections, but L1 INs remain poorly understood. In this work, we systematically examined the distinct dominant electrophysiological features for four unique IN subtypes in L1 that were previously identified from mice of either gender: Canopy cells show an irregular firing pattern near rheobase; neurogliaform cells are late-spiking, and their firing rate accelerates during current injections; cells with strong expression of the α7 nicotinic receptor (α7 cells), display onset (rebound) bursting; vasoactive intestinal peptide (VIP) expressing cells exhibit high input resistance, strong adaptation, and irregular firing. Computational modeling revealed that these diverse neurophysiological features could be explained by an extended exponential-integrate-and-fire neuron model with varying contributions of a slowly inactivating K + channel, a T-type Ca 2+ channel, and a spike-triggered Ca 2+ -dependent K + channel. In particular, we show that irregular firing results from square-wave bursting through a fast-slow analysis. Furthermore, we demonstrate that irregular firing is frequently observed in VIP cells because of the interaction between strong adaptation and a slowly inactivating K + channel. At last, we reveal that the VIP and α7 cell models resonant with alpha/theta band input through a dynamic gain analysis. SIGNIFICANCE STATEMENT In the neocortex, ∼25% of neurons are interneurons. Interestingly, only somas of interneurons reside within layer 1 (L1) of the neocortex, but not of excitatory pyramidal cells. L1 interneurons are diverse and believed to be important in the cortical-cortex interactions, especially top-down signaling in the cortical hierarchy. However, the electrophysiological features of L1 interneurons are poorly understood. Here, we systematically studied the electrophysiological features within each L1 interneuron subtype. Furthermore, we build computational models for each subtype and study the mechanisms behind these features. These electrophysiological features within each subtype should be incorporated to elucidate how different L1 interneuron subtypes contribute to communication between cortexes., (Copyright © 2023 Meng et al.)

Objectives: To evaluate the diagnostic accuracy of fused CBCT images for patients with condylar bone resorption of temporomandibular joint (TMJ) osteoarthrosis., Materials and Methods: Forty-two TMJs from twenty-one patients were included. Bone resorption of condyles evaluated by three experts was used as the reference standard. Three oral and maxillofacial radiology residents evaluated the resorption of condyles with a five-point scale for the four sets of images (two consecutive CBCT images without fusion, fused 2D cross-sectional images, fused 3D images, and combining fused 2D cross-sectional images and fused 3D images) randomly and independently. Each set of images was evaluated at least 1 week apart, and a second evaluation was performed 4 weeks later. Intraclass correlation coefficients were calculated to assess the intra- and inter-observer agreement. The areas under the ROC curves (AUCs) were compared among the four image sets using the Z test., Results: Twenty-four TMJs were determined as condylar bone resorption, and eighteen were determined as no obvious change. The average AUC values from the three observers for the three fused image sets (0.94, 0.93, 0.93) were significantly higher than the image set without fusion (p < 0.01). The intra- and inter-observer agreement on the three fused image sets (0.70-0.89, 0.91-0.92) was higher than the image set without fusion (0.37-0.63, 0.75)., Conclusions: Fused CBCT images of TMJ osteoarthrosis patients can intuitively display the condylar bone resorption and significantly improve the diagnostic accuracy., Clinical Relevance: Fused CBCT images can help clinicians intuitively observe bone changes of the condyle in TMJ osteoarthrosis patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to observe the effects of puerarin on glycolysis and cisplatin sensitivity in oral squamous cell carcinoma (oSCC) cells and to explore the underlying mechanisms. CAL27 cells over- or under-expressing FBXW7 were treated with cisplatin or puerarin, and the levels of proteins involved in glycolysis as well as the activity of the respective enzymes were assessed. Glucose uptake and lactate production were also evaluated, and the IC50 value of cisplatin in CAL27 cells was determined. FBXW7 overexpression significantly downregulated HK2, PKM2, and LDH; suppressed the activity of the corresponding enzymes hexokinase, pyruvate kinase, and lactate dehydrogenase; as well as reduced glucose uptake and lactate production. FBXW7 overexpression was also associated with decreased mTOR phosphorylation and increased cisplatin sensitivity. These effects were partially antagonized by lactate or the mTOR agonist MHY1485. Puerarin suppressed glycolysis by reducing glucose uptake and lactate production, while it promoted cisplatin sensitivity and activated the FBXW7/mTOR signal pathway in a concentration-dependent manner. These effects were antagonized by FBXW7 downregulation or treatment with MHY1485. Our results suggest that FBXW7 improves cisplatin chemosensitivity and suppresses glycolysis in oSCC cells, indicating its promising potential as a target for puerarin to regulate the cisplatin sensitivity of oSCC cells.

Learning to discriminate between different sensory stimuli is essential for survival. In rodents, the olfactory bulb, which contributes to odor discrimination via pattern separation, exhibits extensive structural synaptic plasticity involving the formation and removal of synaptic spines, even in adult animals. The network connectivity resulting from this plasticity is still poorly understood. To gain insight into this connectivity we present here a computational model for the structural plasticity of the reciprocal synapses between the dominant population of excitatory principal neurons and inhibitory interneurons. It incorporates the observed modulation of spine stability by odor exposure. The model captures the striking experimental observation that the exposure to odors does not always enhance their discriminability: while training with similar odors enhanced their discriminability, training with dissimilar odors actually reduced the discriminability of the training stimuli. Strikingly, this differential learning does not require the activity-dependence of the spine stability and occurs also in a model with purely random spine dynamics in which the spine density is changed homogeneously, e.g., due to a global signal. However, the experimentally observed odor-specific reduction in the response of principal cells as a result of extended odor exposure and the concurrent disinhibition of a subset of principal cells arise only in the activity-dependent model. Moreover, this model predicts the experimentally testable recovery of odor response through weak but not through strong odor re-exposure and the forgetting of odors via exposure to interfering odors. Combined with the experimental observations, the computational model provides strong support for the prediction that odor exposure leads to the formation of odor-specific subnetworks in the olfactory bulb., Competing Interests: The authors have declared that no competing interests exist.

Cyclosporine (CsA) is a component of the first-line treatment for acquired aplastic anemia (acquired AA) in pediatric patients. This study aimed to develop a population pharmacokinetic (PK) model of CsA in Chinese pediatric patients with acquired AA to inform individual dosage regimens. A total of 681 CsA whole blood concentrations and laboratory data of 157 pediatric patients with acquired AA were retrospectively collected from two hospitals in Shanghai. A nonlinear mixed-effect model approach was used to build the population PK model. Potential covariate effects of age, body weight, and biochemical measurements (renal and liver functions) on CsA PK disposition were evaluated. Model fit was assessed using the basic goodness of fit and a visual predictive check. The CsA concentration data were accurately described using a two-compartment disposition model with first-order absorption and elimination. Body weight value was implemented as a fixed allometric function on all clearance and volume of distribution parameters. Total bilirubin level was identified as a significant covariate on apparent clearance (CL/F), with a 1.07% reduction per 1 nmol/L rise in total bilirubin level. The final estimates for CL/F and central volume (Vc/F) were 29.1 L/h and 325 L, respectively, for a typical 28 kg child. Other covariates (e.g., gender, age, albumin, hemoglobin, hematocrit, serum creatinine, and concomitant medication) did not significantly affect the PK properties of CsA. This population PK model, along with a maximum a posteriori Bayesian approach, could estimate individual PK parameters in pediatric patients with acquired AA to conduct individual CsA therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2022 Gao, Bian, Qiao, Qian, Li, Shen, Miao, Yu, Meng, Zhu, Jiang, Le, Yu, Wang and Zhai.)

Hemichannels (HCs)/gap junctions (GJs) and immunoglobulin (Ig)-like domain-containing proteins (IGLDCPs) are involved in the innate-adaptive immune response independently. Despite of available evidence demonstrating the importance of HCs/GJs and IGLDCPs in initiating, implementing, and terminating the entire immune response, our understanding of their mutual interactions in immunological function remains rudimentary. IGLDCPs include immune checkpoint molecules of the immunoglobulin family expressed in T and B lymphocytes, most of which are cluster of differentiation (CD) antigens. They also constitute the principal components of the immunological synapse (IS), which is formed on the cell surface, including the phagocytic synapse, T cell synapse, B cell synapse, and astrocytes-neuronal synapse. During the three stages of the immune response, namely innate immunity, innate-adaptive immunity, and adaptive immunity, HCs/GJs and IGLDCPs are cross-activated during the entire process. The present review summarizes the current understanding of HC-released immune signaling factors that influence IGLDCPs in regulating innate-adaptive immunity. ATP-induced "eat me" signals released by HCs, as well as CD31, CD47, and CD46 "don't eat me" signaling molecules, trigger initiation of innate immunity, which serves to regulate phagocytosis. Additionally, HC-mediated trogocytosis promotes antigen presentation and amplification. Importantly, HC-mediated CD4 + T lymphocyte activation is critical in the transition of the innate immune response to adaptive immunity. HCs also mediate non-specific transcytosis of antibodies produced by mature B lymphocytes, for instance, IgA transcytosis in ovarian cancer cells, which triggers innate immunity. Further understanding of the interplay between HCs/GJs and IGLDCPs would aid in identifying therapeutic targets that regulate the HC-Ig-like domain immune response, thereby providing a viable treatment strategy for immunological diseases. The present review delineates the clinical immunology-related applications of HC-Ig-like domain cross-activation, which would greatly benefit medical professionals and immunological researchers alike. HCs/GJs and IGLDCPs mediate phagocytosis via ATP; "eat me and don't eat me" signals trigger innate immunity; HC-mediated trogocytosis promotes antigen presentation and amplification in innate-adaptive immunity; HCs also mediate non-specific transcytosis of antibodies produced by mature B lymphocytes in adaptive immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Meng, Chen, Ahmadian, Zan, Luo and Jiang.)

Background: The dopamine D2 receptor (DRD2) plays an important role in the increased prolactin (PRL) levels associated with the pathogenesis of antipsychotic drugs (ADs). Elevated prolactin levels can affect people's quality of life. Maiya alkaloids has been used to treat diseases associated with high PRL levels. Maiya, is a processed product of the mature fruits of Hordeum vulgare L. (a gramineous plant) after sprouting and drying and also a common Chinese herbal drug used in the clinic, is traditionally used to treat abnormal lactation, and is currently used clinically for the treatment of abnormal PRL levels. Aims: Epigenetic mechanisms can be related to DRD2 expression. We investigated the role of DRD2 methylation in the induction of PRL expression by ADs and the mechanism underlying the effects of total barley maiya alkaloids (TBMA) on this induction. Methods: The methylation rate of DRD2 in 46 people with schizophrenia who took risperidone was detected by MassARRAY sequencing. Humans were long term users of Ris. Seventy Sprague Dawley female rats were divided into seven groups. A rat model of risperidone-induced PRL was established, and the potential protective effects of TBMA and its components [e.g., hordenine (Hor)] on these increased PRL levels were investigated. The PRL concentration was detected by Enzyme-linked immunosorbent assay. PRL, DRD2, and DNA methyltransferase (DNMT1, DNMT3α, and DNMT3β) protein and mRNA expression were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The positive rate of methylation in the DRD2 promoter region of rats was detected by MassARRAY sequencing. Results: Clinical studies showed that the positive rate of DRD2 methylation associated with increased PRL levels induced by ADs was significantly higher than in the normal prolactinemia (NPRL) group. In vivo and vitro, TBMA and Hor inhibited this induction of PRL expression and increased DRD2 expression by inhibiting the expression of the DNMTs. Conclusions: TBMA and hordenine increased DRD2 expression by inhibiting DNMT-dependent DRD2 methylation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, -Zhu, Zhang, Meng, Wu, Wang, Wu, Zou, Fang, An and Chen.)

A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Chen, Cai, Yan, Peng, Li, Cui, Han, Zhang, Meng, Tang, Cai, Long and Luo.)

Objectives: To evaluate the diagnostic efficacy of CBCT-MRI fused image for anterior disc displacement and bone changes of temporomandibular joint (TMJ), which are the main imaging manifestations of temporomandibular disorders (TMD)., Methods: Two hundred and thirty-one TMJs of 120 patients who were diagnosed with TMD were selected for the study. The anterior disc displacement, bone defect and bone hyperplasia evaluated by three experts were used as a reference standard. Three residents individually evaluated all the three sets of images, which were CBCT images, MRI images and CBCT-MRI fused images from individual CBCT and MRI images in a random order for the above-mentioned three imaging manifestations with a five-point scale. Each set of images was observed at least 1 week apart. A second evaluation was performed 4 weeks later. Intra- and interobserver agreements were assessed using the intraclass correlation coefficient (ICC). The areas under the ROC curves (AUCs) of the three image sets were compared with a Z test, and p < 0.05 was considered statistically significant., Results: One hundred and forty-five cases were determined as anterior disc displacement, 84 cases as bone defect and 40 cases as bone hyperplasia. The intra- and interobserver agreements in the CBCT-MRI fused image set (0.76-0.91) were good to excellent, and the diagnostic accuracy for bone changes was significantly higher than that of MRI image set ( p ＜0.05)., Conclusions: CBCT-MRI fused images can display the disc and surrounding bone structures simultaneously and significantly improve the observers' reliability and diagnostic accuracy, especially for inexperienced residents.

Introduction: Abnormal expression of ionotropic glutamate receptor NMDA type subunit 1, the key subunit of the NMDA receptor, may be related to many neuropsychiatric disorders. In this study, we explored the functional sequence of the 5' regulatory region of the human GRIN1 gene and discussed the transcription factors that may regulate gene expression., Materials and Methods: Twelve recombinant pGL3 vectors with gradually truncated fragment lengths were constructed, transfected into HEK-293, U87, and SK-N-SH cell lines, and analyzed through the luciferase reporter gene assay. JASPAR database is used to predict transcription factors., Results: In SK-N-SH and U87 cell lines, regions from -337 to -159 bp, -704 to -556 bp inhibited gene expression, while -556 to -337 bp upregulated gene expression. In HEK-293 and U87 cell lines, the expression of fragment -1703 to + 188 bp was significantly increased compared to adjacent fragments -1539 to + 188 bp and -1843 to + 188 bp. The protein expressions of fragments -2162 to + 188 bp and -2025 to + 188 bp, -1539 to + 188 bp and -1215 to + 188 bp, -1215 to + 188 bp and -1066 to + 188 bp were significantly different in HEK-293 and SK-N-SH cells. According to the predictions of the JASPAR database, the transcription factors REST, EGR1, and CREB1/HIC2 may bind the DNA sequences of GRIN1 gene from the -337 to -159, -556 to -337, and -704 to -556, respectively. In addition, zinc finger transcription factors may regulate the expression of other differentially expressed fragments., Conclusions: Abnormal transcription regulation in the proximal promoter region of GRIN1 (-704 to + 188 bp) may be involved in the course of neuropsychiatric diseases., (Copyright © 2021. Published by Elsevier B.V.)

Background: Group B streptococcus (GBS) is a leading cause of serious infection in infants. Understanding its regional molecular epidemiology is helpful for regulating efficient prevention practice., Methods: A retrospective study was conducted to collected data from infants and pregnant women with culture-proven GBS disease in the largest women and children's medical center in Shanxi between January 2017 and September 2019. All GBS isolates were analyzed by multi-locus sequence typing (MLST) as well as distribution of pilus island (PI) genes., Results: A total of 54 GBS isolates were obtained from 36 (66.7%) pregnant women and 18 (33.3%) infants with invasive disease. Among invasive GBS strains, the most common sequence type was ST10 (72.2%, P < 0.05), followed by ST23 and ST19. The ST10 strain was also the leading sequence type in colonizing pregnant women (44.4%, P < 0.05). All of the isolates carried at least one pilus island. The most frequently detected pilus island was PI-1+PI-2a (85.2%, P < 0.05), followed in turn by PI-2a and PI-2b., Conclusions: Our study demonstrates that one hypervirulent clone, sequence type 10, accounts for a large proportion of invasive GBS disease in infants and colonizing pregnant women, and the PI-1+PI-2a sub-lineages should be noted in infant infections., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2020. Published by Elsevier B.V.)

High-dose methotrexate (HD-MTX) is widely used in pediatric acute lymphoblastic leukemia (ALL) treatment regimens. In this study, we aimed to develop a population pharmacokinetic (PK) model of HD-MTX in Chinese pediatric patients with ALL for designing personalized dosage regimens. In total, 4,517 MTX serum concentration data for 311 pediatric patients with ALL, aged 0.75-15.2 years and under HD-MTX treatment, were retrospectively collected at a tertiary Children's Hospital in China. The non-linear mixed-effect model was used to establish the population PK model, using NONMEM software. The potential covariate effects of age, body weight, and biochemical measurements (renal and liver function) on MTX PK disposition were investigated. The model was then evaluated using goodness-of-fit, visual predictive check. MTX PK disposition was described using a three-compartment model reasonable well. Body weight, implemented as a fixed allometric function on all clearance and volume of distribution parameters, showed a substantial improvement in model fit. The final population model demonstrated that the MTX clearance estimate in a typical child with body weight of 19 kg was 6.9 L/h and the central distribution of volume estimate was 20.7 L. The serum creatinine significantly affected the MTX clearance, with a 0.97% decrease in clearance per 1 μmol/L of serum creatinine. Other covariates (e.g., age, sex, bilirubin, albumin, aspartate transaminase, concomitant medication) did not significantly affect PK properties of MTX. The proposed population PK model could describe the MTX concentration data in Chinese pediatric patients with ALL. This population PK model combined with a maximum a posteriori Bayesian approach could be used to estimate individual PK parameters, and optimize personalized MTX therapy in target patients, thus aiming to reduce toxicity and improve treatment outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Qian, Zhu, Yu, Miao, Meng, Jiang, Wang and Zhai.)

Background: Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and bone formation. The aim of the present study was to explore the effects of HDAC4 on Interleukin 1 beta (IL-1β)-induced chondrocyte extracellular matrix degradation and whether it is regulated through the WNT family member 3A (WNT3A)/β-catenin signaling pathway., Methods: Primary chondrocytes (CC) and human chondrosarcoma cells (SW1353 cells) were treated with IL-1β and the level of HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 cells was silenced using small interfering RNA to detect the effect of HDAC4 knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by IL-1β. After transfection with HDAC4 plasmids, the overexpression efficiency was examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the levels of MMP3 and MMP13 were assayed using Western blotting. After incubation with IL-1β, the translocation of β-catenin into the nucleus was observed using immunofluorescence staining in SW1353 cells to investigate the activation of the WNT3A/β-catenin signaling pathway. Finally, treatment with WNT3A and transfection with glycogen synthase kinase 3 beta (GSK3β) plasmids were assessed for their effects on HDAC4 levels using Western blotting., Results: IL-1β downregulated HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown increased the levels of MMP3 and MMP13, which contributed to the degradation of the extracellular matrix. Overexpression of HDAC4 inhibited IL-1β-induced increases in MMP3 and MMP13. IL-1β upregulated the levels of WNT3A, and WNT3A reduced HDAC4 levels in SW1353 cells. GSK-3β rescued IL-1β-induced downregulation of HDAC4 in SW1353 cells., Conclusion: HDAC4 exerted an inhibitory effect on IL-1β-induced extracellular matrix degradation and was regulated partially by the WNT3A/β-catenin signaling pathway., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objectives: To evaluate the diagnostic efficacy of CBCT-MRI fused images for articular disc calcification of temporomandibular joint (TMJ)., Materials and Methods: Twenty patients (24 TMJs) whose image examinations showed dense bodies in the TMJ space were included in the study. The locations of dense bodies evaluated by the three experts were used as a reference standard. Three oral and maxillofacial radiology residents evaluated whether the dense bodies were disc calcification or not, with a five-point scale for four sets of images (CBCT alone, MRI alone, both CBCT and MRI observed at a time, and CBCT-MRI fused images) randomly and independently. Each set of images was observed at least 1 week apart. A second evaluation was performed after 4 weeks. Intraclass correlation coefficients were calculated to assess the intra- and inter-observer agreement. The areas under the ROC curves (AUCs) were compared between the four image sets using Z test., Results: Ten cases were determined as articular disc calcifications, and fourteen cases were recognized as loose bodies in the TMJ spaces. The average AUC index for the CBCT-MRI fused images was 0.95 and significantly higher than the other sets (p < 0.01). The intra- and inter-observer agreement in the CBCT-MRI fused images (0.90-0.91, 0.93) was excellent and higher than those in the other images., Conclusions: CBCT-MRI fused images can significantly improve the observers' reliability and accuracy in determining articular disc calcification of the TMJ., Clinical Relevance: The multimodality image fusion is feasible in detecting articular disc calcification of the TMJ which are hard to define by CBCT or MRI alone. It can be utilized especially for inexperienced residents to shorten the learning curve and improve diagnostic accuracy.

Objective: To detect the expression of cartilage oligomeric matrix protein (COMP) in the synovial chondromatosis of the temporomandibular joint (TMJSC), and to discuss the possible interactions between COMP, transforming growth factor (TGF)-β3, TGF-β1 and bone morphogenetic protein-2 (BMP-2) in the development of this neoplastic disease., Methods: Patients in Peking University School and Hospital of Stomatology from January 2011 to February 2020 were selected, who had complete medical records, TMJSC was verified histologically after operation. The expressions of COMP, TGF-β3, TGF-β1 and BMP-2 in the TMJSC of the temporomandibular joint were detected by immunohistochemistry and quantitative real-time PCR (RT-PCR) at the protein level and mRNA level respectively, compared with the normal synovial tissue of temporomandibular joint. The histological morphology, protein expression and distribution of TMJSC tissues were observed microscopically, and the positive staining proteins were counted and scored. SPSS 22.0 statistical software was used to analyze the expression differences between the related proteins in TMJSC tissue and the normal synovial tissue of temporomandibular joint and to compare their differences. P < 0.05 indicated that the difference was statistically significant., Results: Immunohistochemical results showed that the positive expression of COMP in TMJSC tissues was mostly found in synovial tissues and chondrocytes adjacent to synovial tissues, and the difference was statistically significant, compared with the normal temporomandibular joint synovial tissues. The positive expression of COMP was significantly different between recurrent TMJSC and non-recurrent ones. The positive expressions of TGF-β3, TGF-β1 and BMP-2 were higher than the normal synovial tissue, and were also mostly found in the synovial cells and adjacent chondrocytes, which was further confirmed by Western blot. According to the RT-PCR results, the expressions of COMP , TGF-β3 , TGF-β1 and BMP-2 in TMJSC were higher than those in the normal synovial tissue., Conclusion: The expression of COMP in TMJSC of temporomandibular joint increased significantly, compared with the normal synovial tissue. There may be interactions between COMP and cytokines related to the proliferation and differentiation, like TGF-β3, TGF-β1 and BMP-2, which may play a potential role in the pathogenesis of TMJSC.

Purpose: Abnormal expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor may potentially increase the susceptibility to neuropsychiatric diseases. The purpose of this study was to investigate the functional sequence of the 3'UTR of the human GRIN1 gene, which encodes the GluN1 receptor to determine the effect on the expression of GluN1 receptor., Methods: We transferred seven recombinant pmirGLO recombinant vectors containing the 3'UTR truncated fragment of the GRIN1 gene into HEK-293, SK-N-SH, and U87 cell lines and compared the relative fluorescence intensity of adjacent length fragments. The TargetScan database was used to predict miRNAs. Then, miRNA mimics/inhibitors were co-transfected into the three cell lines with the 3'UTR of GRIN1 (pmirGLO - GRIN1), to investigate their influence on GRIN1 gene expression., Results: Compared with the pmirGLo-Basic vector, the relative fluorescence intensity of the complete GRIN1 gene 3'UTR recombinant sequence -27 bp - +1284 bp (the next base of the stop codon is +1) was significantly decreased in all three cell lines. The relative fluorescence intensities were significantly different between -27 bp - +294 bp and -27 bp - +497 bp regions, and between -27 bp - +708 bp and -27 bp - +907 bp regions. According to the prediction of the TargetScan database and analysis, miR-212-5p, miR-324-3p and miR-326 may bind to +295 bp - +497 bp, while miR-491-5p may bind to +798 bp - +907 bp. After co-transfection of miRNA mimic/inhibitor or mimic/inhibitor NC with a recombinant vector in the 3'UTR region of GRIN1 gene, we found that has-miR-491-5p inhibited GRIN1 expression significantly in all three cell lines, while has-miR-326 inhibitor upregulated GRIN1 expression in HEK-293 and U87 cells., Conclusion: miR-491-5p may bind to the 3'UTR of the GRIN1 gene (+799 bp - +805 bp, the next base of the stop codon is +1) and down-regulate gene expression in HEK-293, SK-N-SH, and U87 cell lines, which implicates a potential role of miR-491-5p in central nervous system diseases., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2020 Liu et al.)

The objective of this study was to summarize diagnostic points and treatment strategies for diffuse tenosynovial giant cell tumours (D-TSGCTs) of the temporomandibular joint (TMJ), and to evaluate the expression of proteins related to bone destruction and recurrence. The clinical and histopathological characteristics of 24 cases were analysed retrospectively. TRAP staining and immunohistochemical staining for MMP-9, MMP-13, and Ki-67 were performed. The median age of the patients was 45.5 years; the female to male ratio was 1.7:1. In 11 cases (45.8%), skull base destruction seen on computed tomography was confirmed by surgery. Computer-assisted navigation was performed in six cases. Four patients received adjuvant radiotherapy after first surgery. Five patients had recurrent lesions. Multinucleated giant cells were positive for TRAP, MMP-9, and MMP-13. The average Ki-67 index of the recurrent cases was significantly higher than that of the non-recurrent ones (P<0.05). This study demonstrates the aggressive and recurrent nature of D-TSGCT occurring in the TMJ. Computer-assisted navigation is helpful to protect vital structures and determine margins. Adjuvant postoperative radiotherapy is recommended for local control of residual or recurrent tumour. In conclusion, MMP-9 and MMP-13 may play a role in bone destruction of D-TSGCT, and the Ki-67 index has predictive significance for recurrence., (Copyright © 2020 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Prolactinomas are harmful to human health, and the clinical first-line treatment drug is bromocriptine. However, 20% prolactinomas patients did not respond to bromocriptine. Hordenine is an alkaloid separated from Fructus Hordei Germinatus, which showed significant antihyperprolactinemia activity in rats. The aim of this study was to explore the effect and mechanism of hordenine on prolactinomas in rats. The study used estradiol to induce prolactinomas, which caused the activation of the pituitary mitogen-activated protein kinase (MAPK) pathway in rats significantly. The treatment of hordenine restored estradiol, induced the overgrowth of pituitary gland, and reduced the prolactin (PRL) accumulation in the serum and pituitary gland of rats by blocking the MAPK (p38, ERK1/2, and JNK) activation and production of inflammatory cytokines, tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ), and interleukin-6 (IL-6). The antiprolactinoma effect of hordenine was mediated by inhibiting the MAPK signaling pathway activation in rats., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Xiong Wang et al.)

The original version of this article unfortunately contained mistakes in Fig. 2c, d and Funding section.

Background: Surgical treatment is indicated for unstable acromioclavicular (AC) joint dislocation. The hook plate (HP) technique is a commonly used treatment method, but the use of the suture button (SB) technique is increasing., Purpose: To conduct a meta-analysis of clinical studies evaluating patient outcomes between the SB and HP techniques for acute unstable AC joint dislocation., Study Design: Meta-analysis., Methods: A literature search of the Embase, PubMed, and Cochrane Library databases was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Cohort studies and case-control studies comparing the SB and HP procedures for acute unstable AC joint dislocation were included. Statistical analysis was performed with RevMan (v 5.3.5)., Results: Eight clinical studies that met the inclusion criteria were identified and included a total of 204 patients treated with the SB technique and 195 patients with the HP technique. Patients treated with the SB technique had a higher Constant score (mean difference [MD], 3.95; 95% CI, 1.20-6.70; P = .005) and a lower visual analog scale pain score (MD, -0.75; 95% CI, -1.12 to 0.37; P < .0001) when compared with the HP technique. No significant differences in operation time (MD, -0.38; 95% CI, -7.14 to 6.37; P = .91), coracoclavicular distance (MD, -0.07; 95% CI, -0.49 to 0.35; P = .75), complications (odds ratio, 0.59; 95% CI, 0.22-1.54; P = .28), and loss of reduction (odds ratio, 2.55; 95% CI, 0.66-9.83; P = .17) were found between the SB and HP techniques. The subgroup analysis showed that the arthroscopic SB technique resulted in a higher Constant score (MD, 6.75; 95% CI, 4.21-9.29; P < .00001) as compared with the HP technique, but no differences were observed between the open SB and HP techniques (MD, 0.69; 95% CI, -0.82 to 2.20; P = .37)., Conclusion: This meta-analysis demonstrated that the SB technique resulted in better functional outcomes and a reduced visual analog scale pain score when compared with the HP technique. However, for operation time, coracoclavicular distance, complications, and loss of reduction, there were no statistically significant differences between the techniques. Compared with the open procedure, arthroscopic SB may be superior for better functional outcomes.

Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, while relapse and refractory ALL remains a leading cause of death in children. However, paired ALL samples of initial diagnosis and relapse subjected to next-generation sequencing (NGS) could construct clonal lineage changes, and help to explore the key issues in the evolutionary process of tumor clones. Therefore, we aim to analyze gene alterations during the initial diagnosis and relapse of ALL patients and to explore the underlying mechanism., Methods: Targeted exome sequencing technology was used to detect molecular characteristic of initial diagnosis and relapse of ALL in 12 pediatric patients. Clinical features, treatment response, prognostic factors and genetic features were analyzed., Results: In our 12 paired samples, 75% of pre-B-cell acute lymphoblastic leukemia (B-ALL) patients had alterations in the Ras pathway ( NRAS , KRAS , NF1 , and EPOR ), and Ras mutation are very common in patients with ALL relapse. TP53 mutations mainly existed in the primary clones and occurred at the initial diagnosis and relapse of ALL. Relapse-associated genes such as NT5C2 and CREBBP were observed in patients with ALL relapse; however, all patients included in this study had gene abnormalities in the Ras pathway, and NT5C2 and CREBBP genes may collaboratively promote ALL relapse., Conclusions: Among the 12 ALL patients, Ras pathway mutations are common in ALL relapse and may be associated with other recurrence-related genes alterations. The study with paired samples could improve the understanding of ALL relapse., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Translational Pediatrics. All rights reserved.)

The Schizophrenia Psychiatric GWAS Consortium (PGC) has identified the rs1625579 polymorphism in the MIR137 gene, which encodes miR-137, as the strongest new association with schizophrenia in the European population. However, whether the influence of rs1625579 on schizophrenia in the Asian population is consistent with these results remains unclear. A total of 21 studies (9878 schizophrenic patients and 9447 control subjects) that met the inclusion criteria were included in our meta-analysis. Pooled analysis, subgroup analysis, sensitivity analysis and publication bias were performed. The T allele, TT genotype and TT + GG genotype were associated with schizophrenia as risk factors. Subgroup analysis shows that no heterogeneity existed in the European and Asian populations. Our meta-analysis found that the Rs1625579 polymorphism in the MIR137 gene was associated with the risk of schizophrenia. The current findings provide a reference for case-control studies of schizophrenia in the future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study identified a transcription factor that might bind to the 5' regulatory region of the HTR1A and explored the potential effect on 5-HT1A receptor expression. Based on JASPAR predictions, the binding of the transcription factor was demonstrated using the electrophoretic mobility shift assay (EMSA). Vectors over-expressing the transcription factor were co-transfected into HEK-293 and SK-N-SH cells with the recombinant pGL3 vector, and relative fluorescence intensity was measured to determine regulatory activity. Additionally, the qRT-PCR and Western blot were also used to identify whether the transcription factor modulated the endogenous expression of 5-HT1A receptor. The results suggest that the transcription factor CCAA/T enhancer binding protein beta (CEBPB) likely binds to the -1219 to -1209 bp (ATG+1) region of the HTR1A . Two sequences located in the -722 to -372 bp and -119 to +99 bp were also identified. Although the effect of CEBPB on endogenous 5-HT1A receptor expression was not significant, it exhibited the strong inhibition on the relative fluorescence intensity and the mRNA level of HTR1A . CEBPB inhibited the human HTR1A expression by binding to the sequence -1219 - -1209 bp. This is useful and informative for ascertaining the regulation of 5-HT1A receptor and mental diseases.

The calcification of the articular disc is an uncommon lesion, usually discovered in hips, elbows, and shoulders, but rarely in temporomandibular joints (TMJ). The TMJ disc calcification may be related to pain and limitation of the mandibular mobility, however, most of the patients were asymptomatic. A 61-year-old female was referred to our hospital after a maxillofacial fist injury, bilateral TMJ disc calcifications were found accidentally by radiological examination. Here the significance of image fusion of cone-beam computed tomography and magnetic resonance imaging (MRI) in the diagnosis of this lesion was emphasized.

In order to study the molecular differences between type 2 diabetes mellitus (T2DM) and T2DM with depression (DD), we aimed to screen the differential expression of lncRNA, mRNA, and circRNA in the blood of patients with T2DM and DD. Based on the self-rating depression scale (SDS), patient health questionnaire 9 (PHQ9), blood glucose and HbA1c, we divided the patients into T2DM and DD group. Peripheral blood was collected from the two groups of patients to perform lncRNA, mRNA, and circRNA expression profiling and screening DD-related specific molecules. Subsequently, bioinformatics analysis was performed to investigate the functions of differentially expressed genes (DEgenes). Finally, RT-PCR and lncRNA-mRNA regulatory network was performed to verify the expressions of lncRNAs and mRNAs related to the occurrence and development of DD. 28 lncRNAs, 107 circRNAs, and 89 mRNAs were identified in DD differential expression profiles. GO and pathway analysis found that 20 biological process (BP) related entities and 20 pathways associated with DD. The analysis shows that the genes that are differentially expressed in the DD group involved in the development of the neuropsychiatric system, immunity, and inflammation. Then, we screening for the important DElncRNA and mRNA associated with DD were verified by RT-PCR experiments and the results of RT-PCR were consistent with the sequencing results. LncRNA, circRNA, and mRNA differential expression profiles exist in DD patients compared with T2DM. The lncRNA-mRNA regulatory network analysis confirmed the crosslinking and complex regulation patterns of lncRNA and mRNA expression and verified the authenticity of the regulatory network.

Background: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by molecular aberrations. Recently, genetic profiling has been fully investigated on ALL; however, the interaction between its genetic alterations and clinical features is still unclear. Therefore, we investigated the effects of genetic variants on ALL phenotypes and clinical outcomes., Methods: Targeted exome sequencing technology was used to detect molecular profiling of 140 Chinese pediatric patients with ALL. Correlation of genetic features and clinical outcomes was analyzed., Results: T-cell ALL (T-ALL) patients had higher initial white blood cell (WBC) count (34.8×10 9 /L), higher incidence of mediastinal mass (26.9%), more relapse (23.1%), and enriched NOTCH1 (23.1%), FBXW7 (23.1%) and PHF6 (11.5%) mutations. Among the 18 recurrently mutated genes, SETD2 and TP53 mutations occurred more in female patients (P=0.041), NOTCH1 and SETD2 mutants were with higher initial WBC counts (≥50×10 9 /L) (P=0.047 and P=0.041), JAK1 mutants were with higher minimal residual disease (MRD) level both on day 19 and day 46 (day 19 MRD ≥1%, P=0.039; day 46 MRD ≥0.01%, P=0.031) after induction chemotherapy. Multivariate analysis revealed that initial WBC counts (≥50×10 9 /L), MLLr , and TP53 mutations were independent risk factors for 3-year relapse free survival (RFS) in ALL. Furthermore, TP53 mutations, age (<1 year or ≥10 years), and MLLr were independently associated with adverse outcome in B-cell ALL (B-ALL)., Conclusions: MLLr and TP53 mutations are powerful predictors for adverse outcome in pediatric B-ALL and ALL. Genetic profiling can contribute to the improvement of prognostication and management in ALL patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Prolonged or repeated exposure to ketamine, a common anesthetic in pediatrics, has been shown to induce neurotoxicity and long-term neurocognitive deficits in the developing brain. Therefore, identification of potential therapeutic targets for preventing or alleviating such neurodegeneration and neuroapoptosis induced by ketamine is urgently needed. Remote ischemic preconditioning of the limb provides neuroprotection in different models of cerebral injury. Thus, the present study aimed to assess whether remote ischemic preconditioning could have a neuroprotective effect against neurotoxicity induced by ketamine. In our study, 96 newborn rats were assigned to one of four groups, including control, remote ischemic preconditioning, ketamine, and remote ischemic preconditioning plus ketamine. Ketamine was administered intraperitoneally in six doses of 20 mg/kg at 2-h intervals. Limb remote ischemic preconditioning comprised four ischemia (5 min)/reperfusion (5 min) cycles in the right hind limb using an elastic rubber band tourniquet. Histopathological characteristics of cerebral damage were assessed by H&E staining and transmission electron microscopy. TUNEL assay, immunohistochemical staining and immunoblot were employed to evaluate neural cell apoptosis. Learning and memory were evaluated using the Morris water maze. The results showed increased cleaved caspase-3 protein levels in the cerebral cortex and the hippocampal CA1 region, severe cell damage and DNA breakage, and decreased spatial learning and memory abilities in the ketamine group in comparison with controls. Notably, these changes were significantly reduced by remote ischemic preconditioning. These findings suggest that remote ischemic preconditioning ameliorates neuroapoptosis and neurocognitive impairment after repeated ketamine exposure in newborn rats.

Many studies have suggested that organic matter (OM) substantially reduces the bioavailability and risks of mercury (Hg) in soils and sediments; however, recent reports have supported that OM greatly accelerates Hg methylation and increases the risks of Hg exposure. This study aims to summarize the interactions between Hg and OM in soils and sediments and improve our understanding of the effects of OM on Hg methylation. The results show that OM characteristics, promotion of the activity of Hg-methylating microbial communities, and the microbial availability of Hg accounted for the acceleration of Hg methylation which increases the risk of Hg exposure. These three key aspects were driven by multiple factors, including the types and content of OM, Hg speciation, desorption and dissolution kinetics and environmental conditions.

Objectives:: To present a method for image fusion of cone beam CT (CBCT)/CT and MRI and to explore whether the image data sets fused in such a way could aid the detection of temporomandibular joint (TMJ) anatomical structures and lesions., Methods:: There were five cases included in this study. One case was space occupying lesion giant cell tumour of tendon sheaths, one case was chronic inflammation in the condyle, one case was articular disc calcification of the bilateral TMJs, and the other two cases were TMJ disorders (anterior disc displacement without reduction). The digital imaging and communications in medicine format data of CT/CBCT and MRI of the cases were collected, and then imported to the Amira visual software where the registration process was conducted. Based on the different scan model, the registration process could be separated into automatic registration of CT/CBCT with quadrature slice MR images and the semi-automatic registration of CT/CBCT with oblique slice MR images by altering the registration parameters. Rigid transform model and the similarity metric of normalization mutual information was used for registration in the present study., Results:: The relationship between the soft mass and hard tissue was shown clearly in the fused images when compared to sole observation of CBCT/CT or MR images. The fused images could define the tumour outline and the destructive bone clearly in the same image. The fused results helped the observers to ensure uncertain defects which could not be confirmed only by one image data set., Conclusions:: The CT/CBCT and MR images could be fused to aid detection of TMJ anatomical structures and related lesions.

Objective: To investigate the effect of electroacupuncture (EA) at different time-points on postoperative gastrointestinal function in patients undergoing colorectal cancer surgery., Methods: Eighty patients with colorectal cancer undergoing laparotomy were randomly assigned to intravenous anesthesia, EA A, EA B, and EA C groups ( n ＝20 cases in each group). All the patients in the four groups received intravenous anesthesia with midazolam, sufentanil, cisatracurium besylate and Propofol, postoperative gastrointestinal decompression and drug analgesia. EA (2－3 mA, 2 Hz) was applied to Zhongwan (CV 12) and Tianshu (ST 25), Neiguan (PC 6), Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39) on the right side for 30 min, once (one day before surgery) in the EA A group, twice (one day and 30 min before surgery) in the EA B group, and 3 times (one day, 30 min before and one day after surgery) in the EA C group. The acupoints used after surgery were PC 6, ST 36, ST 37 and ST 39. The time of postoperative ventilation, defecation, food-intake and water drinking, stomach tube removal and abdominal drainage tube removal, the volumes of stomach tube drainage and abdominal drainage, and postoperative adverse reactions were recorded., Results: The first ventilation time, after surgery in the EA C group was significantly earlier than those in the intravenous anesthesia, EA A and EA B groups ( P <0.05); and the water intake and abdomicnal drainage tube removal time after surgery in the EA C group were significantly earlier than those in the intravenous anesthesia group ( P <0.05). No significant differences were found among the 4 groups in the time of defecation, food intake, stomach tube removal, stomach tube drainage and abdominal drainage volumes, and numbers of patients with nausea, vomiting, fever and other adverse reactions ( P >0.05)．., Conclusion: EA treatment combined with intravenous anesthesia conducted before and after surgery is effective in promoting the recovery of gastrointestinal function in patients undergoing colorectal cancer laparotomy, and is obviously better than simple pre-operative EA.

Objective: To investigate the prevalence and resistance changes of carbapenem-resistant Enterobacteriaceae (CRE) strains isolated from children patients of Chinese Bacterial Resistance Surveillance Network (CHINET) from 2005 to 2017. Methods: Antimicrobial susceptibility testing was carried out by disk diffusion method (KB method) and automated systems. Results were analyzed according to the Clinical and Laboratory Standards Institute (CLSI) 2017 edition standards. Results: Among the 4 481 CRE clinical strains, the overall prevalence of CRE in children was 6.4%, including 8.8% in neonatal period, 7.3% in infancy, 3.8% in early childhood, 4.0% in preschool, 4.7% at school age and 7.4% of puberty. The CRE prevalence of citrobacter spp . remained stable in 2005-2017, whereas other bacteria showed an upward trend, which was higher than that of the adult group ( P< 0.01). Among the 4 481 CRE strains, there were 2 905 strains of Klebsiella spp. (64.8%), 813 strains of Escherichia coli (18.1%), 549 strains of Enterobacter spp. (12.3%), and 65 strains of Citrobacter spp. (1.5%). Among the 4 481 CRE strains, 20.7%, 13.3%, and 11.8% were from the intensive care unit (ICU), neonatal department and internal medicine wards, respectively. Specimens were distributed as respiratory (42.8%), urine (26.3%), and blood (14.9%). The results of antimicrobial susceptibility testing exhibited that the CRE strains were highly resistant to most commonly used antimicrobial agents in clinical practice, such as imipenem, meropenem and ertapenem, as well as penicillins and cephalosporins, etc. Conclusion: The prevalence of CRE strains in children is increasing year by year, and their antimicrobial resistance to common antibacterial agents in clinical practice is extremely serious, to which serious attention needs to be paid. According to the results of antimicrobial susceptibility testings, the antibacterial agents should be rationally selected to effectively control the spread of CRE.

Aims: Postmenopausal osteoporosis is a bone metabolism disease that is caused by an imbalance between bone-resorbing osteoclast and bone-forming osteoblast actions. Herein, we describe the role of troxerutin (TRX), a trihydroxyethylated derivative of rutin, in ovariectomy (OVX)-induced osteoporosis and its effects on the regulation of osteoclasts and osteoblasts., Main Methods: In vivo, OVX female mice were intraperitoneally injected with either saline, 50 mg/kg TRX, or 150 mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses, histological analyses, and biomechanical testing. In vitro, RAW264.7 cell-derived osteoclasts and MC3T3-E1 cell-derived osteoblasts were treated with different concentrations of TRX to examine the effect of TRX on osteoclastogenesis and bone resorption, as well as on osteogenesis and mineralization., Key Findings: In this study, we demonstrated that TRX prevented cortical and trabecular bone loss in ovariectomized mice by reducing osteoclastogenesis and promoting osteogenesis in vivo. In vitro, TRX inhibited the formation and activity of RAW264.7-derived osteoclasts and the expression of nuclear factor of activated T-cells 1 and cathepsin K. Meanwhile, TRX improved the osteogenesis and mineralization of MC3T3-E1 by enhancing the expression of Runt-related transcription factor 2, Osterix, and collagen type 1 alpha 1., Significance: Our data demonstrated that TRX could prevent OVX-induced osteoporosis and be used in a novel treatment for postmenopausal osteoporosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Several studies have been performed to investigate the association between SMAD3 gene polymorphism and osteoarthritis (OA), but the results were inconclusive. This study aims to determine whether SMAD3 polymorphism is associated with risk of OA., Method: A comprehensive literature search in PubMed, Embase, and ISI Web of Science for relevant studies was performed. After extracting data from eligible studies, we chose the fixed or random effect model according to the heterogeneity test. Estimation of publication bias and sensitivity analysis were conducted to confirm the stability of this meta-analysis., Results: In total, 10 studies from 6 articles with 5093 OA patients and 5699 controls were enrolled in this meta-analysis. The combined results revealed significant association between SMAD3 rs12901499 polymorphism and the risk of OA (allele model: OR 1.21, 95% CI 1.07-1.38). Subgroup analysis revealed that G allele increased the risk of OA in Caucasians, but not in Asians (allele model: Caucasians: OR 1.31, 95% CI 1.18-1.44; Asians: OR 1.24, 95% CI 0.95-1.61). And the pooled results revealed significant association between SMAD3 rs12901499 polymorphism and both knee and hip OA (knee OA: OR 1.18, 95% CI 1.04-1.34; hip OA: OR 1.31, 95% CI 1.18-1.44)., Conclusion: The current meta-analysis revealed that the G variant of SMAD3 rs12901499 polymorphism increased the risk of OA in Caucasians. Further well-designed studies with larger sample size in different ethnic populations are required to confirm these results.

Prophenoloxidase (proPO) activating system is an important immune response for arthropods. β-1, 3-glucanase related protein (previously named as lipopolysaccharide and β-1, 3-glucan binding protein (LGBP) in crustaceans) is a typical pattern recognition receptor family involved in the proPO activation by recognizing the invading microbes. In this study, we pay special attention to a bacteria-induced β-1,3-glucanase related protein from red swamp crayfish Procambarus clarkii, an important aquaculture specie in China. This protein, designated PcBGRP, was found a typical member of crustacean BGRP family with the glucanase-related domain and the characteristic motifs. PcBGRP was expressed in hemcoyes and hepatopancreas, and its expression could be induced by the carbohydrate and bacteria stimulants. The induction by lipopolysaccharide (LPS) and β-1,3-glucan (βG) was more significant than by peptidoglycan (PG). The response of PcBGRP to the native Gram-negative bacterial pathogen Aeromonas hydrophila was more obvious than to Gram-positive bacteria. Using RNA interference and recombinant protein, PcBGRP was found to protect crayfish from A. hydrophila infection revealed by the survival test and morphological analysis. A mechanism study found PcBGRP could bind LPS and βG in a dose-dependent manner, and the LPS recognizing ability determined the Gram-negative bacterium binding activity of PcBGRP. PcBGRP was found to enhance the PO activation both in vitro and in vivo, and the protective role was related to the PO activating ability of PcBGRP. This study emphasized the role of BGRP family in crustacean immune response, and provided new insight to the immunity of red swamp crayfish which suffered serious disease during the aquaculture in China., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Oscillators coupled in a network can synchronize with each other to yield a coherent population rhythm. How do multiple such rhythms interact with each other? Do these collective oscillations synchronize like individual oscillators? We show that this is not the case: for strong, inhibitory coupling rhythms can become synchronized by noise. In contrast to stochastic synchronization, this new mechanism synchronizes the rhythms even if the noisy inputs to different oscillators are completely uncorrelated. Key for the synchrony across networks is the reduced synchrony within the networks: it substantially increases the frequency range across which the networks can be entrained by other networks or by periodic pacemaker-like inputs. We demonstrate this type of robust synchronization for different classes of oscillators and network connectivities. The synchronization of different population rhythms is expected to be relevant for brain rhythms.

Objective: To investigate the association between single nucleotide polymorphisms (SNP) of ADAMTS14 gene rs4747096 and osteoarthritis of the temporomandibular joint in Chinese Han females., Methods: As a case-control study, a total of 213 Chinese Han females were involved in the present study, which contained 103 temporomandibular joint osteoarthritis patients and 110 healthy people who had no symptoms or signs of temporomandibular joint osteoarthritis as control. Peripheral blood samples were collected from each participant. Genomic DNAs of temporomandibular joint osteoarthritis patients and healthy control were extracted from peripheral venous blood, which were stored in -80 °C refrigerator by using DNA extraction kits. The designed primers were used for polymerase chain reaction (PCR) amplification of specific DNA fragments. Genotype was determined by sequencing the PCR products. The software Chromas 2.22 was used to analyze the genotype. The genotype distributions, allele frequencies and genetic models between the patients and controls were compared. The age distribution was checked by t-test. Genotype and allele frequency were detected by Chi-square test., Results: In the present study, there were no significant differences between the osteoarthritis patients and healthy controls in terms of age. The genotype distribution was in accordance with Hardy-Weinberg equilibrium in the two groups. The genotype frequency of the ADAMTS14 (rs4747096) in the experimental group was 38.8% (AA), 55.4% (AG), and 5.8% (GG), respectively. The genotype frequency in the control group was 40.9% (AA), 43.6% (AG), and 15.5% (GG), respectively. The difference of genotype frequency of the ADAMTS14 (rs4747096) was significant between the experimental group and the control group (P=0.047). There was no significant difference in allele frequency between the two groups (P=0.415). AA and AG genotypes significantly increased the risk of the disease compared with GG in dominant model (OR=1.114, 95% CI: 1.015-1.223, P=0.028)., Conclusion: A significant correlationship was found between the ADAMTS14 (rs4747096) SNP and the temporomandibular joint osteoarthritis in Chinese Han females. The distribution of rs4747096 may be different between temporomandibular joint osteoarthritis and healthy population.