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Juan-Juan Cheng,1 Xing-Dong Ma,1 Gao-Xiang Ai,1 Qiu-Xia Yu,2 Xiao-Ying Chen,1 Fang Yan,3,4 Yu-Cui Li,1 Jian-Hui Xie,3,5,6 Zi-Ren Su,1 Qing-Feng Xie3,4 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 3The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 4Li Ke and Qi Yu-ru Academic Experience Inheritance Studio, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 5State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, People’s Republic of ChinaCorrespondence: Qing-Feng Xie; Zi-Ren Su, Email xieqingfeng1@gzucm.edu.cn; suziren@gzucm.edu.cnPurpose: Gouty arthritis could be triggered by the deposition of monosodium uric acid (MSU) crystals. Palmatine (PAL), a protoberberine alkaloid, has been proven to possess compelling health-beneficial activities. In this study, we aimed to explore the effect of PAL on LPS plus MSU crystal-stimulated gouty arthritis in vitro and in vivo.Methods: PMA-differentiated THP-1 macrophages were primed with LPS and then stimulated with MSU crystal in the presence or absence of PAL. The expression of pro-inflammatory cytokines and oxidative stress-related biomarkers and signal pathway key targets were determined by ELISA kit, Western blot, immunohistochemistry and qRT-PCR, respectively. In addition, the anti-inflammatory and antioxidant activities of PAL on MSU-induced arthritis mice were also evaluated.Results: The results indicated that PAL (20, 40 and 80 μM) dose-dependently decreased the mRNA expression and levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β), IL-6, IL-18 and tumor necrosis factor alpha (TNF-α)). The levels of superoxide dismutase (SOD) and glutathione (GSH) were remarkably enhanced, while the level of malondialdehyde (MDA) was reduced. Western blot analysis revealed that PAL appreciably inhibited NF-κB/NLRP3 signaling pathways through inhibiting the phosphorylation of p-65 and IκBα, blocking the expression of NLRP3, ASC, IL-1β and Caspase-1, as well as enhancing the antioxidant protein expression of Nrf2 and HO-1. In vivo, PAL attenuated MSU-induced inflammation in gouty arthritis, as evidenced by mitigating the joint swelling, and decreasing the productions of IL-1β, IL-6, IL-18, TNF-α and MDA, while enhancing the levels of SOD and GSH. Moreover, PAL further attenuated the infiltration of neutrophils into joint synovitis.Conclusion: PAL protected against MSU-induced inflammation and oxidative stress via regulating the NF-κB/NLRP3 and Nrf2 pathways. PAL may represent a potential candidate for the treatment of gouty arthritis.Keywords: palmatine, NF-κB/Nrf2 signal pathways, NLRP3 inflammasome, gouty arthritis

Temporomandibular joint or related masticatory muscle pain represents the most common chronic orofacial pain condition. Patients frequently report this kind of pain after dental alterations in occlusion. However, lack of understanding of the mechanisms of occlusion-related temporomandibular joint and muscle pain prevents treating this problem successfully. To explore the relationship between improper occlusion (occlusal interference) and masticatory muscle pain, we created an occlusal interference animal model by directly bonding a crown to a maxillary molar to raise the masticating surface of the tooth in rats. We raised the occlusal surface to three different heights (0.2, 0.4, and 0.6mm), and for one month we quantitatively measured mechanical nociceptive thresholds of the temporal and masseter muscles on both sides. Results showed a stimulus-response relationship between the height of occlusal interference and muscle hyperalgesia. Removal of the crown 6 days after occlusal interference showed that the removal at this time could not terminate the 1 month duration of mechanical hyperalgesia in the masticatory muscles. Lastly, we systemically administered NMDA antagonist MK801 (0.2, 0.1, and 0.05 mg/kg) to the treated rats and found that MK801 dose dependently attenuated the occlusal interference-induced hyperalgesia. These findings suggest that occlusal interference is directly related to masticatory muscle pain, and that central sensitization mechanisms are involved in the maintenance of the occlusal interference-induced mechanical hyperalgesia. [ABSTRACT FROM AUTHOR]

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients'suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Background: Stroke often results in significant respiratory dysfunction in patients. Respiratory muscle training (RMT) has been proposed as a rehabilitative intervention to address these challenges, but its effectiveness compared to routine training remains debated. This systematic review and meta-analysis aim to evaluate the effects of RMT on exercise tolerance, muscle strength, and pulmonary function in post-stroke patients., Aim: To systematically assess the efficacy of RMT in improving exercise tolerance, respiratory muscle strength, and pulmonary function in patients recovering from a stroke, and to evaluate whether RMT offers a significant advantage over routine training modalities in enhancing these critical health outcomes in the post-stroke population., Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, a comprehensive search across PubMed, Embase, Web of Science, and the Cochrane Library was conducted on October 19, 2023, without temporal restrictions. Studies were selected based on the predefined inclusion and exclusion criteria focusing on various forms of RMT, control groups, and outcome measures [including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and 6-min walking test (6MWT)]. Only randomized controlled trials (RCTs) were included. Data extraction and quality assessment were conducted independently by two reviewers using the Cochrane Collaboration's risk of bias tool. Statistical analyses, including those using the fixed-effect and random-effects models, sensitivity analysis, and publication bias assessment, were performed using Review Manager software., Results: A total of 15 RCTs were included. Results indicated significant improvements in MIP (12.51 cmH 2 O increase), MEP (6.24 cmH 2 O increase), and various pulmonary function parameters (including FEV1, FVC, MVV, and PEF). A substantial increase in 6MWT distance (22.26 meters) was also noted. However, the heterogeneity among studies was variable, and no significant publication bias was detected., Conclusion: RMT significantly enhances walking ability, respiratory muscle strength (MIP and MEP), and key pulmonary function parameters (FEV1, FVC, MVV, and PEF) in post-stroke patients. These findings support the incorporation of RMT into post-stroke rehabilitative protocols., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Microplastics (MPs), as a new type of pollutant, are widely detected in sewage treatment plants. Currently, research on MPs in traditional sewage treatment systems has mainly been focused on the pollution level and distribution characteristics, with a lack of studying the impact of MPs on the sludge granulation. In order to explore the effect of MPs on the granulation process, a microplastic exposure test was conducted by adding polyethylene terephthalate microplastics (PET-MPs), which are widespread in the environment. The operating performance of the system, extracellular polymeric substance (EPS) composition, and flora enrichment were analyzed on the sludge granulation. The results showed that the exposure of PET-MPs significantly accelerated the sludge granulation process, whereas the increase in EPS content dominated by PN enhanced the sludge surface hydrophobicity; the granulation rate and EPS secretion were proportional to the exposed particle size. Microplastics and EPS secretions synergistically promoted the formation of granular sludge. However, continuous microplastic exposure led to deterioration of the system decontamination performance and inhibited the degradation process of pollutants, with the most negative effect of nitrite nitrogen accumulation under 250 μm PET-MPs exposure, as high as (5.08±0.24) mg·L -1 . The high-throughput sequencing revealed that the microbial community diversity fell in the experimental group. The dominant bacteria at the phylum level were Proteobacteria and Bacteroidota on the sludge granulation. Rhodocyclaceae, Sphingomonadaceae, Flavobacteriaceae, and Rhodanobacteraceae promoted flocculation by increasing EPS secretion. The decrease in Comamonadaceae and Chitinophagaceae weakened the ammonia and nitrite oxidation capacity of the system, whereas the decrease in Rhodobacteraceae, Hyphomonadaceae, and Xanthomonadaceae inhibited the removal of nitrate nitrogen.

Tetracycline antibiotics (TCs), one of the important antibiotic groups, have been widely used in human and veterinary medicines. Their residues in foodstuff, soil and sewage have caused serious threats to food safety, ecological environment and human health. Here, we reviewed the potential harms of TCs residues to foodstuff, environment and human beings, discussed the luminescence and aptamer sensors based analytical determination, adsorptive removal, and degradation strategies of TCs residues from a recent 5-year period. The advantages and intrinsic limitations of these strategies have been compared and discussed, the potential challenges and opportunities in TCs residues degradation have also been deliberated and explored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Dental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI)., Methods: Expressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM., Results: Upregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats., Conclusions: These results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI., (© 2023. The Author(s).)

This study aimed to evaluate somatosensory function in Chinese patients with trigeminal neuralgia (TN) using a standard quantitative sensory testing (QST) battery and electrophysiological tests consisting of contact heat-evoked potentials (CHEPs) and blink reflex (BR). Twenty patients with TN and 20 sex- and age-matched healthy controls were recruited for this study. A standard QST protocol recommended by the German Research Network on Neuropathic Pain was carried out on the patients' painful and contralateral faces, the controls' right faces, and all participants' right hands. The CHEPs and BR were recorded at the Cz electrode and bilateral lower bellies of the orbicularis oculi, respectively, with thermal stimuli applied to both sides of the patient's face and the control's right face. The cold detection threshold, heat pain threshold, and mechanical pain threshold on the painful face were lower than those of healthy controls (P < 0.05), whereas the cold pain threshold and mechanical detection threshold were higher (P < 0.05) on the painful faces than those of the contralateral faces from patients or healthy controls. Mechanical pain sensitivity was higher in both test sites than in healthy controls (P < 0.05). Significantly longer N latencies (P < 0.05) and lower N-P amplitudes (P < 0.01) were detected in the patients' painful sites than in the contralateral sites and those of healthy controls. Comprehensive somatosensory abnormalities were found in painful facial sites in patients with TN, suggesting disturbances in the processing of somatosensory stimuli. Deficiencies in electrophysiological tests further revealed unilaterally impaired function of the trigeminal pathway in TN patients., (© 2022. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF., 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 Liu, Xie, Liu, Wang, Mu, Zhang, Zhao, Yuan, Guo, Wang, Xiang, Song, Jiang, Xiang and Cui.)

The Energy iNNovation's XuanLong-50 is a spherical torus experiment with up to 10 s plasma operation duration. A 3 J/50 Hz pulsed laser is used in the Thomson scattering diagnostic system that is developed to measure the time evolutions of plasma electron temperature and density profiles. The expected laser pulse number is about 7.5 × 10 6 /year with a power load of 150 W. To meet at least 1-year lifetime requirement, a Chevron type beam dump with polished molybdenum plates is designed and fabricated, which absorbs the laser beam energy in a 3D structure to reduce the laser fluence deposited on the material surface. To prevent the backscattered stray light from interfering with the Thomson scattering measurements, a 7.5 m beam path with folding mirrors is set between the beam dump and the plasma scattering volumes. Details of the beam dump design procedure including the laser beam profile control, multi-pulse laser damage threshold, heat dissipation, Zemax modeling, folding mirror selection, and beam path enclosure are presented together with the testing results.

Purpose: This study compared the effect of indobufen with that of aspirin on platelet function in patients with stable coronary heart disease after percutaneous coronary intervention (PCI). Methods: Patients with stable coronary heart disease who had undergone PCI and received dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg once daily) for at least 12 months were allocated to receive indobufen 100 mg twice daily + clopidogrel 75 mg once daily, clopidogrel 75 mg once daily alone, indobufen 100 mg twice daily alone, and aspirin 100 mg once daily alone for 1 month each in an open-label crossover manner. Platelet function was assessed by using the rates of arachidonic acid (AA)-induced platelet aggregation (AA-PAR) and adenosine diphosphate (ADP)-induced platelet aggregation (ADP-PAR) measured by light transmission aggregometry, the platelet reactivity index measured by vasodilator-stimulated phosphoprotein (PRI-VASP), and the plasma and urinary thromboxane B 2 (TXB 2 ) concentrations recorded at baseline and during each treatment phase. Results: Of 56 patients enrolled, 52 completed the study. The AA-PAR was lower in the indobufen alone group than in the aspirin alone group [5.21% (3.39, 7.98) vs. 5.27% (4.06, 6.60), p = 0.038], while biologically, a difference of 0.06% may represent no significant difference; there was no significant between-group difference in the plasma [531.16 pg/ml (203.89, 1035.06) vs. 373.93 pg/ml (194.04, 681.71), p = 0.251] or urinary [3951.97 pg/ml (2006.95, 6077.01) vs. 3610.48 pg/ml (1664.60, 6247.61), p = 0.717] TXB 2 concentration. When the aspirin + clopidogrel group and indobufen + clopidogrel group were compared, similar results were found for AA-PAR [3.97% (3.05, 5.12) vs. 3.83% (3.10, 5.59), p = 0.947] and both plasma [849.47 pg/ml (335.96, 1634.54) vs. 455.41 pg/ml (212.47, 1489.60), p = 0.629], and urinary [4122.97 pg/ml (2044.96, 7459.86) vs. 3812.81 pg/ml (1358.95, 6021.07), p = 0.165] TXB 2 concentrations. ADP-PAR was lower in the clopidogrel alone group than in the indobufen alone group (47.04% ± 16.89 vs. 61.7% ± 10.50, p < 0.001), as was PRI-VASP (66.53% ± 18.06 vs. 77.72% ± 19.87, p = 0.002). Conclusion: These findings suggest that indobufen has antiplatelet effects similar to those of aspirin in patients with stable coronary heart disease after PCI, and may be an alternative for patients with aspirin intolerance after coronary stenting., 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 Shi, Luo, Zhang, Wang, Zhao, Xie, Liu, Liu, Jiang and Zheng.)

Polychromators are most frequently used in Thomson scattering (TS) diagnostics to analyze the scattered light spectrum and intensity so that the plasma electron temperature (T e ) and density (n e ) can be derived. For T e measurements, the spectral response of the polychromator channels and the relative spectral responsivities need to be calibrated. The spectral response is calibrated with a bromine tungsten lamp and a monochromator in a conventional way. A novel method for calibrating the relative spectral responsivities of the polychromators is described in detail. A broadband pulsed Light Emission Diode (LED) is used, which has a spectral irradiance similar to that of the TS spectrum, and the LED can be driven in pulse mode with the pulse width similar to the TS signal pulse width of about 10-20 ns full width at half maximum. This new method allows for the calibration to be done after the polychromator is fully installed, and in situ system calibration can be easily performed, showing the advantages of accuracy, simplicity, efficiency, and flexibility. For n e measurements, absolute sensitivity calibration is done by Rayleigh scattering with argon gas. Formulas for calculating the plasma density from the calibration data and the polychromator signals from the off-laser wavelength channels are presented.

A 15-point Thomson scattering diagnostic system is developed for ENN's spherical torus experiment XuanLong-50 (EXL-50). A BeamTech laser with 3 J/pulse (1064 nm wavelength) at 50 Hz repetition rate is chosen for measurements during EXL-50 plasma operations. To enable measurements at low density (∼0.5 × 10 18  m -3 ) plasma operations, the opto-mechanical subsystems are carefully designed to maximize the collection and transmission of the scattered light and to minimize the stray light level. In addition, the high bandwidth trans-impedance amplifiers and segmented high speed waveform digitizers allow for the application of muti-pulse averaging to further improve the signal-to-noise ratio. Details of the diagnostic system are described and initial experimental results are presented.

Background: The real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have reported conflicting findings. Our study aimed to provide the direct comparison evidence of different NOACs for VTE patients in clinical practice settings., Methods: Search of the medical literature was conducted using PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library from inception to March 22, 2021. Among the 19,996 citations retrieved, a total of 63,144 patients from 6 studies were analyzed. Clinical outcomes included recurrent VTE, death, and different bleeding events., Results: Adjusted hazard ratio (HR) analysis suggested that apixaban had significant lower bleeding riskthan rivaroxaban (major, minor and any bleeding: HR = 0.61, 0.56, 0.70; p = 0.008, < 0.0001, 0.006, respectively), but no statistics difference found in recurrent VTE events (HR = 1.02, 95% confidence interval (CI) 0.71-1.47, p = 0.93). There was no significant difference of major bleeding between dabigatran and rivaroxaban (odds ratios (OR) = 0.41, 95% CI 0.09-1.90, p = 0.25), apixaban and dabigatran (OR 0.64, 95% CI 0.15-2.72, p = 0.83). No significant difference was found in the comparison of edoxaban and other NOACs in VTE recurrence, major bleeding and composite outcome., Conclusions: In the prevention of bleeding events, apixaban was associated with a lower risk than rivaroxaban, but equivalent efficacy for different NOACs in prevention of recurrent VTE. Evidence generated from the meta-analysis based on real-world data can help to guide selection between apixaban and rivaroxaban in routine clinical practice., Trial Registration: This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology statements and was registered with PROSPERO (CRD42019140553)., (© 2022. The Author(s).)

Objective: To investigate the effect of porous surface morphology of zirconia on the proliferation and differentiation of osteoblasts., Methods: According to different manufacturing and pore-forming methods, the zirconia specimens were divided into 4 groups, including milled sintering group (M-Ctrl), milled porous group (M-Porous), 3D printed sintering group (3D-Ctrl) and 3D printed porous group (3D-Porous). The surface micromorphology, surface roughness, contact angle and surface elements of specimens in each group were detected by scanning electron microscope (SEM), 3D laser microscope, contact angle measuring device and energy-dispersion X-ray analysis, respectively. MC3T3-E1 cells were cultured on 4 groups of zirconia discs. The cell morphology of MC3T3-E1 cells on zirconia discs was eva-luated on 1 and 7 days by SEM. The cell proliferation was detected on 1, 3 and 5 days by cell counting kit-8 (CCK-8). After osteogenic induction for 14 days, the relative mRNA expression of alkaline phosphatase ( ALP ), type Ⅰ collagen ( Colla1 ), Runt-related transcription factor-2 ( Runx2 ) and osteocalcin ( OCN ) in MC3T3-E1 cells were detected by real-time quantitative polymerase chain reaction., Results: The pore size [(419.72±6.99) μm] and pore depth [(560.38±8.55) μm] of 3D-Porous group were significantly larger than the pore size [(300.55±155.65) μm] and pore depth [(69.97±31.38) μm] of M-Porous group ( P < 0.05). The surface of 3D-Porous group appeared with more regular round pores than that of M-Porous group. The contact angles of all the groups were less than 90°. The contact angles of 3D-Ctrl (73.83°±5.34°) and M-Porous group (72.7°±2.72°) were the largest, with no significant difference between them ( P >0.05). Cells adhered inside the pores in M-Porous and 3D-Porous groups, and the proliferation activities of them were significantly higher than those of M-Ctrl and 3D-Ctrl groups after 3 and 5 days' culture ( P < 0.05). After 14 days' incubation, ALP , Colla1 , Runx2 and OCN mRNA expression in 3D-Porous groups were significantly lower than those of M-Ctrl and 3D-Ctrl groups ( P < 0.05). Colla1 , Runx2 and OCN mRNA expressions in M-Porous group were higher than those of 3D-Porous group ( P < 0.05)., Conclusion: The porous surface morphology of zirconia can promote the proliferation and adhesion but inhibit the differentiation of MC3T3-E1 cells.

Objective: To investigate the influence of chronic masseter hyperalgesia induced by 17β-estradiol (E2) and experimental occlusal interference (EOI) on underlying mechanism in hippocampus of ovariectomized (OVX) rats., Methods: In the study, 32 OVX rats were randomly divided into 4 groups (8 rats/group): The control group was OVX group, and 0 μg/d E2 (vehicle) injection was started 7 d after OVX without EOI; in the experimental group (1) OVX + E2 group, 80 μg/d E2 injection was started 7 d after OVX without EOI; in the experimental group (2) OVX + EOI group, vehicle injection was started 7 d after OVX and EOI was applied 17 d after OVX; in the experimental group (3) OVX + E2 + EOI group, 80 μg/d E2 injection was started 7 d after OVX and EOI was applied 17 d after OVX. Bilateral masseter muscle mechanical withdrawal thresholds were measured before OVX, 7 days after OVX (before E2 injection), 17 days after OVX (10 days after E2 injection and before EOI) and 24 days after OVX (7 days after EOI). Immunofluorescence staining was used to reveal phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2)-positive neurons in CA3 of hippocampus. The protein expression of p-ERK1/2 in hippocampus was detected using Western Blot., Results: Compared with the control group [left side: (135.3±8.5) g, right side: (135.4±10.8) g], bilateral masseter muscle mechanical withdrawal thresholds of OVX+E2 group [left side: (113.3±5.6) g, right side: (112.5 ± 5.6) g] and OVX+EOI group [left side: (93.3±5.4) g, right side: 90.8±5.5) g] were decreased ( P < 0.01). Bilateral masseter muscle mechanical withdrawal thresholds were significantly lower in OVX+E2+EOI group [left side: (81.2±6.2) g, right side: 79.8±7.7) g] than in the control, OVX+E2 and OVX+EOI groups ( P < 0.05). The proportion of p-ERK1/2 positive neurons in the CA3 region of the hippocampus was increased in the control, OVX+E2, OVX+EOI and OVX+E2+EOI groups in turn, and the difference between the groups was statistically significant ( P < 0.05). p-ERK1/2 protein expression was increased in the control, OVX+E2 and OVX+EOI groups in turn, but the difference was not statistically significant ( P >0.05). p-ERK1/2 expression was significantly higher in OVX+E2+EOI group than in the other three groups ( P < 0.05)., Conclusion: High concentration of E2 could exacerbated EOI-induced chronic masseter hyperalgesia in ovariectomized rats, and its central mechanism may be related to the upregulation of the phosphorylation of ERK1/2 in hippocampus.

Background: Oro-facial pain is more prevalent in women than in men, and oestrogen may underlie this sex difference. Genistein reversed the potentiation of 17β-estradiol (E2) on glutamate-induced acute masseter nociceptive behaviour, but its role in dental experimental occlusal interference (EOI)-induced chronic masseter hyperalgesia remains unclear., Objective: This study aimed to investigate sex differences, and to explore the role and underlying mechanisms of genistein in E2-potentiated EOI-induced chronic masseter hyperalgesia in rats., Methods: Female and male rats were prepared to compare the sex differences of masseter hyperalgesia induced by EOI using a 0.4-mm-thick metal crown. Female rats were ovariectomised (OVX) and treated with E2 and genistein, followed by EOI. The head withdrawal threshold (HWT) was examined to assess masseter sensitivity. The protein expression of transient receptor potential vanilloid-1 (TRPV1) in the trigeminal ganglion (TG) was detected using western blotting. Immunofluorescence staining was used to reveal the colocalisation of oestrogen receptors (ERs) with TRPV1 and the percentage of TRPV1-positive neurons in the TG., Results: To some extent, female rats displayed enhanced sensitivity to EOI-induced chronic masseter hyperalgesia compared with males. Female rats showed the lowest HWT in the pro-oestrus phase. Pre-treatment with genistein antagonised E2 potentiation in EOI-induced masseter hyperalgesia and blocked the effect of E2 by downregulating TRPV1 protein expression and the percentage of TRPV1-positive neurons in the TG., Conclusion: Female rats showed greater masseter hyperalgesia than males under EOI. Genistein antagonised the facilitation of EOI-induced chronic masseter hyperalgesia by E2 probably through inhibiting TRPV1 in the TG., (© 2021 John Wiley & Sons Ltd.)

Background: Astrocytes in the rostral ventromedial medulla (RVM) contribute to descending pain modulation, but their role in oro-facial pain induced by persistent experimental dental occlusal interference (PEOI) or following EOI removal (REOI) is unknown., Objective: To explore the involvement of RVM astrocytes in PEOI-induced oro-facial hyperalgesia or its maintenance following REOI., Methods: Male rats were randomly assigned into five groups: sham-EOI, postoperative day 6 and 14 of PEOI (PEOI 6 d and PEOI 14 d), postoperative day 6 following REOI on day 3 (REOI 3 d) and postoperative day 14 following REOI on day 8 (REOI 8 d). The nociceptive head withdrawal threshold (HWT) and activities of RVM ON- or OFF-cells were recorded before and after intra-RVM astrocyte gap junction blocker carbenoxolone (CBX) microinjection. RVM astrocytes were labelled immunohistochemically with glial fibrillary acidic protein (GFAP) and analysed semi-quantitatively., Results: Persistent experimental dental occlusal interference-induced oro-facial hyperalgesia, as reflected in decreased HWTs, was partially inhibited by REOI at day 3 but not at day 8 after EOI placement. Increased GFAP-staining area occurred only in REOI 8 d group in which CBX could inhibit the maintained hyperalgesia; CBX was ineffective in inhibiting hyperalgesia in PEOI 14 d group. OFF-cell activities showed no change, but the spontaneous activity and responses of ON-cells were significantly enhanced that could be suppressed by CBX in REOI 8 d group., Conclusion: Rostral ventromedial medulla astrocytes may not participate in PEOI-induced oro-facial hyperalgesia or hyperalgesia inhibition by early REOI but are involved in the maintenance of oro-facial hyperalgesia by late REOI., (© 2021 John Wiley & Sons Ltd.)

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/μl (IQR = 96-289 cells/μl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/μl) and AIDS (median CD4 = 97 cells/μl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19., 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 Lin, Lin, Wang, Wen, Xiang, Fan, Li, Wu, Lin, Lin, Sun, Chen, Chen, Lian, Xie, Lin, Xie, Li, Peng, Wang, Lin, Chen, Huang and Fu.)

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17β-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.

Purpose: A meta-analysis was performed to evaluate the correlation between single-nucleotide polymorphisms (SNPs) and risk of statin-induced myopathy (SIM)., Methods: We retrieved the studies published on SIM until April 2019 from the PubMed, Embase, and Cochrane Library databases. We collected data from 32 studies that analyzed 10 SNPs in five genes and included 21,692 individuals and nine statins., Results: The analysis of the heterozygous (p = 0.017), homozygous (p = 0.002), dominant (p = 0.005), and recessive models (p = 0.009) of SLCO1B1 rs4149056 showed that this SNP increases the risk of SIM. Conversely, heterozygous (p = 0.048) and dominant models (p = 0.030) of SLCO1B1 rs4363657 demonstrated that this SNP is associated with a reduced risk of SIM. Moreover, an increased risk of SIM was predicted for carriers of the rs4149056 C allele among simvastatin-treated patients, whereas carriers of the GATM rs9806699 A allele among rosuvastatin-treated patients had a lower risk of SIM., Conclusion: The meta-analysis revealed that the rs4149056 and rs4363657 SNPs in SLCO1B1 and the rs9806699 SNP in GATM are correlated with the risk of SIM.

Objective: To analyze the longitudinal variation of occlusal force distribution and occlusal contact time in posterior implant-supported single crown with the computerized occlusal analysis system. Methods: Partially edentulous patients who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology between December 2012 and December 2013, and had received implant-supported single crown in the posterior region were enrolled. The participants underwent occlusal examinations with the computerized occlusal analysis system at 2 weeks, 3 and 6 months, 1, 2, 3, and 4 years after implant prosthesis delivery. The relative occlusal force (ROF) of implant prostheses, mesial adjacent teeth, and control teeth (corresponding teeth on the contralateral side) were recorded, and implant prosthesis occlusion time ratios (implant prosthesis occlusion time/occlusion time) were calculated. The interproximal contact between implant prostheses and adjacent teeth was evaluated using metal contact gauge and dental floss. Mechanical complications of implant prostheses were recorded. The paired t test or Wilcoxon signed-rank test was used to compare the implant prosthesis occlusion time ratios and ROF of implant prostheses at 2 different times as a self-control. The differences in ROF between implant prostheses and control teeth in the same participant at the same time were also analyzed using paired t test. Using a complementary log-log model, the correlation between the occurrence of veneering material fracture and ROF of implant prosthesis was analyzed with gender, age and follow-up time as the control variables. Results: Thirty-seven posterior fixed implant-supported single crowns in 33 participants, including 16 men and 17 women aged (42.8±12.9) years (23.9 to 70.0 years) were followed up for 2 weeks to 4 years [(38.3±15.2) months]. The ROF of implant prostheses increased significantly ( P <0.01) from 2 weeks [(7.0±4.2)%] to 3 months [(9.9±6.8)%], whereas those of control natural teeth decreased significantly ( P <0.05) from (13.1±6.1)% to (11.4±5.5)%. The ROF of implant prostheses continued to increase from 6 months to 1 year, from 1 year to 2 years and from 2 years to 3 years, with significant differences ( P <0.05). Implant prosthesis occlusion time ratios also increased significantly between 2 weeks and 3 months and between 3 months and 6 months ( P <0.05). No significant differences were found between other time points ( P >0.05). For comparison between implant prosthesis and control teeth at the same time point, the ROF of the implant prostheses [(7.5±4.2)%] were significantly lower than those of the control teeth [(13.8±6.0)%] at 2 weeks ( P <0.01). While at 4 years, ROF of implant prostheses [16.7% (8.6%, 32.4%)] became significantly higher than those of control teeth [9.5% (4.9%, 18.0%)] ( P <0.05). ROF of the implant prostheses did not differ significantly with those of the control teeth in other follow-up time points ( P >0.05). The 4-year cumulative incidence of proximal contact loss rate was 32% (22/68). The incidences of veneering material fracture and prostheses loosening were 16% (6/37) and 8% (3/37), respectively. Logistic regression showed a significant correlation between veneering material fracture and ROF of implant prostheses ( r =0.26, P <0.05). Conclusions: The occlusal force and occlusal contact time of posterior implant-supported single crown change over time in 4-year follow-up period, which is mainly reflected in the increasing occlusal force and occlusal contact time. The occlusion of posterior implant prostheses should be carefully monitored during follow-up examinations, and occlusal adjustment should be considered when necessary.

Occlusal dysesthesia (OD) or phantom bite syndrome refers to a persistent complaint of uncomfortable bite sensation with no obvious occlusal discrepancy. OD is a rare condition, and is usually associated with emotional distress and triggered by dental treatments. The diagnosis and management of OD patients still remains a major challenge for dental practitioners and affected patients. This topical review aims to describe the properties, etiologies, diagnosis, managements and prognosis of OD comprehensively.

Curcumin (CUR) possesses pronounced anti-inflammatory and antioxidant activities. Generally, the clinical application of CUR is restricted due to its apparent unstability and poor absorption, and the biological activities of CUR may be closely associated with its metabolites. Tetrahydrocurcumin (THC) and octahydrocurcumin (OHC) are two major hydrogenated metabolites of CUR with appreciable biological potentials. Here, we comparatively explored the anti-inflammatory and antioxidant activities of CUR, THC, and OHC in lipopolysaccharide- (LPS-) induced RAW264.7 macrophages. The results revealed that CUR, THC, and OHC dose-dependently inhibited the generation of NO and MCP-1 as well as the gene expression of MCP-1 and iNOS. Additionally, CUR, THC, and OHC significantly inhibited NF- κ B activation and p38MAPK and ERK phosphorylation, while substantially upregulated the Nrf2 target gene expression (HO-1, NQO-1, GCLC, and GCLM). Nevertheless, zinc protoporphyrin (ZnPP), a typical HO-1 inhibitor, significantly reversed the alleviative effect of CUR, THC, and OHC on LPS-stimulated ROS generation. These results demonstrated that CUR, THC, and OHC exerted beneficial effect on LPS-stimulated inflammatory and oxidative responses, at least partially, through inhibiting the NF- κ B and MAPKs pathways and activating Nrf2-regulated antioxidant gene expression. Particularly, THC and OHC might exert superior antioxidant and anti-inflammatory activities to CUR in LPS-stimulated RAW264.7 cells, which can be further explored to be a promising novel effective agent for inflammatory treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Qing-Feng Xie et al.)

Objective: To establish the workflow of determining the jaw position of repositioning splint with the aid of digital technique, and to evaluate the accuracy of this workflow and compare the accuracy of raising different vertical dimensions in vitro ., Methods: A volunteer was recruited. The data of full-arch scans, cone beam computed tomography (CBCT) image and ultrasonic jaw motion tracking of the volunteer were acquired. The full-arch scans were merged with the CBCT image, which were then matched to the jaw motion tracking reference system. The jaw position of repositioning splint was determined when the anterior teeth opening was 3 mm and the condyle was in centric relation of the fossa in the sagittal plane. A digital repositioning splint was designed in the software based on virtual articulator and fabricated with additive manufacturing technique. After the splint was tried in, another CBCT image was taken and a qualitative analysis was conducted to compare the position of condyle between these two CBCT images. In the in vitro study, standard dental plaster casts with resin ball markers attached to the base were mounted onto a fully adjustable articulator in the intercuspal position. The dental casts were scanned by an extraoral scanner to establish digital models. The ultrasonic jaw motion tracking device was used to obtain simulated jaw movements on the articulator, which was repeated for three times. The digital models and data of jaw movements were merged in one coordination with the aid of bite forks. The jaw position of repositioning splint was determined by adjusting data of jaw movements, each of which was used to determine three vertical jaw positions 4 mm, 5 mm, and 6 mm with the horizontal jaw position of protrusion 2 mm. The virtual articulators with differently adjusted jaw movements were applied in designing repositioning splints, and the final repositioning splints and virtual jaw relationships were exported in STL format. Then the repositioning splints were fabricated with additive manufacturing technique and tried in plaster casts on the mechanical articulator, which were scanned and the jaw relationships on the mechanical articulator were exported later. The virtual jaw relationships and scanned jaw relationships were registered according to lower models and displacement of upper models was calculated. Ball markers were fit to acquire the coordinates of centers and absolute difference values of centers along three coordinating axes X , Y , and Z were calculated. One-way analysis of variance was conducted using SPSS 18.0 software to compare deviations of the three different vertical jaw relationships in two-side test and the significance level was 0.05., Results: With the aid of multi-source data fusion and individualized jaw motion, the clinical workflow of determining jaw position of repositioning splint was preliminarily established. The designed jaw position was realized on the right and the condyle was more inferior than the designed position on the left. Both displacement of the upper models and absolute difference values of centers showed no significant differences ( P >0.05) in different vertical jaw dimensions. The displacement of the upper models was (0.25±0.04) mm. The absolute difference values of centers along the three coordinating axes X , Y , and Z were respectively (0.08±0.01) mm, (0.30±0.02) mm, and (0.21±0.04) mm., Conclusion: A novel method of determining the jaw position of repositioning splint with the aid of digital technique is established. It is proved to be feasible by try-in after multi-data fusion, computer-aided design and computer-aided manufacturing. As is shown in vitro , it is accurate to apply this method in adjusting jaw position. Further clinical trial will be designed to evaluate its clinical effect.

Objective: To establish a method for the production of digital individual tooth tray based on three-dimensional (3D) scan, computer-aided design (CAD) and 3D printing, and to evaluate the effect of impression taking of full-arch crown abutments by digital individual tooth tray technique and conventional method through in vitro study., Methods: The full crown preparation was performed on all the fourteen resin teeth in a standard model of mandibular dentition. The surface data of prepared abutments was collected by 3D scanning. A new project was created in a dental CAD software including all the fourteen teeth in the mandibular dentition. The design modules of anatomy crown and coping were selected for each tooth. The dentition was divided for three sections: right posterior teeth, anterior teeth, and left posterior teeth areas. The connector design was added between the abutments within the same section. The scanned data of the abutments were imported. The occlusal plane and insertion path were determined. The position of margin line, as well as the shape of anatomy crown and connector as the main body of the individual tooth tray were designed for each abutment. The shape of coping was generated as the space for holding the impression material. The finalized data of the main body was imported into Geomagic software. The retentive attachment was added at the external surface and the tissue stop was formed at the internal surface. The completed individual tooth tray was manufactured by 3D printing with resin material. The data of full-arch crown abutments were modified and printed. The conventional dentition trays A and B, as well as digital individual tooth tray were designed and printed for four copies each. The polyether impressions of the full-arch abutments were made by conventional one-step method using dentition tray A, and by sectional-impression technique using digital individual tooth tray and dentition tray B for four times each. The time spent for each impression taking and the numbers of defects at the shoulder and axial/occlusal surface in each impression were recorded. The impression quality of each abutment was evaluated. The overall quality distribution and the pass rate of abutments between the two methods were analyzed., Results: The impressions made by conventional method had more defects at shoulder than those made by digital individual tooth tray technique. No difference of the number of defects at axial/occlusal surface between the two methods was observed. The digital individual tooth tray technique for the full-arch abutment impression exhibited higher pass rate of abutments and better quality of impression, compared with conventional methods., Conclusion: A new method for the production of digital individual tooth tray based on digital scanning, CAD and 3D printing was established. Compared with conventional method, using digital individual tooth tray technique for impression taking of full-arch abutments can achieve better effect.

Background: Sorafenib is an oral multi-kinase inhibitor that was approved by the US Food and Drug Administration for the treatment of patients with advanced hepatocellular carcinoma (HCC). However, resistance to sorafenib is an urgent problem to be resolved to improve the therapeutic efficacy of sorafenib. As the activation of AKT/mTOR played a pivotal role in sorafenib resistance, we evaluated the effect of a dual mTOR complex 1/2 inhibitor Torin2 on overcoming the sorafenib resistance in HCC cells., Methods: The sorafenib-resistant Huh7 and Hep3B cell lines were established from their parental cell lines. The synergistic effect of sorafenib and Torin2 on these cells was measured by cell viability assay and quantified using the Chou-Talalay method. Apoptosis induced by the combination of sorafenib and Torin2 and the alteration in the specific signaling pathways of interest were detected by Western blotting., Results: Sorafenib treatment inversely inhibited AKT in parental but activated AKT in sorafenib-resistant Huh7 and Hep3B HCC cells, which underscores the significance of AKT activation. Torin2 and sorafenib synergistically suppressed the viability of sorafenib-resistant cells via apoptosis induction. Torin2 successfully suppressed the sorafenib-activated mTORC2-AKT axis, leading to the dephosphorylation of Ser136 in BAD protein, and increased the expression of total BAD, which contributed to the apoptosis in sorafenib-resistant HCC cells., Conclusions: In this study, Torin2 and sorafenib showed synergistic cytostatic capacity in sorafenib-resistant HCC cells, via the suppression of mTORC2-AKT-BAD pathway. Our results suggest a novel strategy of drug combination for overcoming sorafenib resistance in HCC., (Copyright © 2020. Published by Elsevier B.V.)

Background: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients., Methods: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification., Results: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa0 2 /FiO 2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×10 9 /L, neutrophil >5.3×10 9 /L, lymphocyte < 0.73 × 10 9 /L, PaO 2 /FiO 2  < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7., Conclusion: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present study compared performances of the three major methods used for assessing platelet reactivity (PR)-VerifyNow, light transmission aggregometry (LTA) and thromboelastography (TEG)-to predict ischaemic events in patients receiving clopidogrel. PubMed, EMBASE and the Cochrane Library were searched from their inception to April 2019 for prospective studies that examined PR using VerifyNow, LTA or TEG and the incidence of ischaemic events. The investigated diagnostic indices include sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio and area under the receiver operating characteristic curves (AUC) of VerifyNow, LTA and TEG, respectively. A total of 26 prospective studies involving 22 185 patients were included in the analysis. The pooled AUC was 0.71 (95% CI: 0.67-0.75) for VerifyNow, 0.60 (95% CI: 0.55-0.64) for LTA and 0.81 (95% CI: 0.77-0.84) for TEG. Results of indirect comparisons indicated the AUC of VerifyNow was higher than that of LTA (1.18, 95% CI: 1.08-1.30) and lower than that of TEG (0.88, 95% CI: 0.82-0.94). TEG outperformed the other two methods for assessing PR in all predictive measures, including sensitivity, specificity, PLR and NLR. Despite a lack of studies that directly compared the three methods, our findings suggest that TEG should be recommended., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objectives: This study aimed to quantitatively compare the somatosensory function changes of inferior alveolar nerve (IAN) after mandibular third molar extraction with a surgery protocol of coronectomy, as opposed to the conventional method., Materials and Methods: Patients with a lower third molar directly contacting IAN were recruited and assigned either to a test group (coronectomy group) or a control group (conventional extraction). A standardized quantitative sensory testing (QST) battery was performed for four times: one week before surgery and the second, seventh, and 28th days after surgery. Z-scores and the loss/gain coding system were applied for each participant., Results: A total of 140 molars (test group: n = 91, control group: n = 49) were enrolled. The sensitivity of the mechanical detection threshold (MDT) and pressure pain threshold (PPT) significantly increased after surgery more than before surgery in both groups (P ≤ 0.001). After the surgery, the sensitivities of the cold detection threshold (CDT), cold pain threshold (CPT), and heat pain threshold (HPT) were significantly higher in the test group than in the control group (P ≤ 0.027). The risk of IANI was significantly larger (P = 0.041) in the test group than in the control group., Conclusions: QST was a sensitive way to detect somatosensory abnormalities even with no subjective complaint caused by surgery. Coronectomy had less influence on IAN function than conventional total extraction., Clinical Relevance: The somatosensory function changes after mandibular third molar extraction were quantitatively studied, and coronectomy was proved a reliable alternation to reduce IAN injury rate.

Background: Post-liver transplantation (LT) hepatocellular carcinoma (HCC) recurrence still occurs in approximately 20% of patients and drastically affects their survival. This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population., Methods: A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study. Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival., Results: Of the 64 patients with recurrent HCC after LT, those who received radical resection followed by nonsurgical therapy had a median overall survival (OS) of 20.9 months after HCC recurrence, significantly superior to patients who received only nonsurgical therapy (9.4 months) or best supportive care (2.4 months). The one- and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy (93.8%, 52.6%), poor for patients receiving only nonsurgical therapy (30.8%, 10.8%), and dismal for patients receiving best supportive care (0%, 0%; overall P < 0.001). Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months, far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure (12 months, P < 0.001). Compared with tacrolimus-based immunosuppressive therapy, OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence (P = 0.035). Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival., Conclusions: Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence. A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Objective: To choose a suitable efficient concentration of adenosine triphosphate (ATP) which can induce human dental pulp cells (HDPC) differentiate into odontoblast successfully, and explore the role of this concentration of ATP in dentin regeneration in vivo . Methods: HDPC were treated with different concentrations (0, 10, 400, 600, 800 μmol/L) of ATP. Then cell counting kit-8 (CCK-8), quantitative real-time PCR, and Western blotting were used to detect the cell proliferation and the expressions of odontoblastic differentiation related markers, dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP). Alizarin red S staining experiment was used to analyze the effect of ATP on the mineralization ability of HDPC. By the above experiments, the suitable effective concentration of ATP was chosen to pretreat the HDPC for 7 days, then cells were seeded on gelfoam, inserted into the root canal fragment, and subsequently transplanted into the subcutaneous space on the back of immunodeficient mice, after three months, the samples were stained with HE for histological analysis. Results: The CCK-8 results in 5 d showed that 10 μmol/L ATP obviously promoted the proliferation of HDPC, while the 600 and 800 μmol/L ATP apparently inhibited the HDPC proliferation, however, the proliferation in 800 μmol/L ATP group was lower than that of 600 μmol/L ATP group ( P< 0.05). qPCR and Western blotting results showed that the 600 and 800 μmol/L ATP significantly up-regulated the DMP1 and DSPP expressions ( P< 0.05), furthermore, there was no significant difference in the two groups, but no changes were found in other groups ( P> 0.05). After 21 days of culturing, there were obvious mineralization nodules in 600 and 800 μmol/L ATP groups, but no mineralization nodules in other groups. Quantitative analysis of the staining results showed the A value in 0, 10, 400, 600, and 800 μmol/L ATP groups were respectively 1.05±0.15, 1.11±0.23, 1.15±0.17, 3.65±0.30, and 3.40±0.43, and the A value in 600 and 800 μmol/L ATP groups were higher than those of other groups; however, there was no difference in 600 and 800 μmol/L ATP groups. The histological analysis showed that 600 μmol/L ATP could induce the HDPC differentiate into dentin-like structure in the root canal fragment. Conclusions: Therefore, the suitable effective concentration of ATP is 600 μmol/L, which could induce HDPC differentiate into odontoblast-like cells, and form the dentin-like structure in vivo .

Kenaf seed oil was extracted with 3 different solvents, i.e. hexane, ethanol and aqueous enzymatic medium with or without ultrasonic assistance. The synergistic effects of ultrasound and extraction solvent on the content of bioactive compound in kenaf seed oil was investigated. Results show that ultrasound-assisted extraction with hexane obtained the highest yield (84.71%), while yield with aqueous enzymatic medium was the lowest (51.12%). Two endothermic peaks exhibited on the melting curve of kenaf seed oil at the temperature range - 37 to - 25 °C and - 12 to - 2 °C, respectively. Linoleic, oleic and palmitic acid are the major fatty acids, accounting for above 96% of the total fatty acids. The content of vitamin E, phosphatide, total phenols and sterol are 92.38-105.01 mg/100 g oil, 0.38-22.28 g/kg, 0.51-71.02 mg GAE/100 g and 161.79-533.12 mg/100 g, respectively. The solvent employed has significant effect ( p  < 0.05) on the thermal property, fatty acid composition and bioactive constituents of the extracted kenaf seed oil. The oil extracted with ethanol contained more nervonic acid and bioactive components such as β-carotene, phosphatide, total phenols and sterols. The introduction of ultrasound reduced the extraction time remarkably. The results demonstrate that extraction with ethanol combined with ultrasound is an effective method to extract kenaf seed oil, as more reasonable fatty acid composition and higher content of bioactive components can be achieved., (© Association of Food Scientists & Technologists (India) 2020.)

Objective: To compare the orofacial pain sensitivity with operant test and mechanical hyperalgesia with von Frey filaments of two orofacial pain models (EOI: experimental occlusal interference; pIONX: partial infraorbital nerve transection). To investigate the operant and evoked characteristics of EOI-rats., Methods: The orofacial operant behaviors were tested by Ugo Basile Orofacial Stimulation Test System. The mechanical thresholds of vibrissal pads were tested by von Frey filaments. Male Sprague-Dawley rats were randomly divided into eight groups: von Frey group: sham-EOI, EOI, sham-pIONX, pIONX (sham: sham-operated group); operant test group: sham-EOI, EOI, sham-pIONX, pIONX (sham: sham-operated group). The mechanical thresholds and orofacial operant behaviors were tested on pre-operation and post-operation days l, 3, 7, 10, 14 and 21., Results: In pIONX of von Frey group, the mechanical withdrawal threshold decreased from days 1 to 21 (P<0.05), peaking from days 7 to 10, and lasted until the end of the experiment. There was no significant difference between the bilateral sides. In pIONX of operant test group, the total contact time decreased from days 10 to 21 (P<0.05), peaking from days 10 to 14, and lasted until the end of the experiment. In EOI of von Frey group, the mechanical withdrawal threshold decreased from days 3 to 21 (P<0.05), peaking on day 7, and lasted until the end of the experiment. There was no significant difference between the bilateral sides. In EOI of operant test group, the total contact time decreased from days 1 to 21 (P<0.05), peaking from days 7 to 10, and lasting until the end of experiment., Conclusion: Orofacial operant test is a stable method to evaluate orofacial pain behaviors, which could discriminate the feature of neuropathic and EOI orofacial pain. In these two animal models, both of the operant behaviors and the mechanical hyperalgesia exhibited different time courses. Orofacial operant test provides a novel method for evaluating the orofacial pain sensitivity and studying the orofacial pain mechanism thoroughly.

Liver transplantation is the most effective treatment for end-stage liver disease, and early graft dysfunction often occurs after surgery. Early liver dysfunction after liver transplantation has become one of the complications after liver transplantation, which seriously affects the graft and patient survival. Therefore, reducing its occurrence can be an important means to improve the prognosis of recipients after liver transplantation. This paper discusses the research progress on the definition, influencing factors, and prognosis and prediction model in order to provide better prevention and effective reference for improving the success rate and prognosis of early liver dysfunction in recipients after liver transplantation.

Objective: To evaluate the accuracy of digital models obtained from intraoral scanning of edentulous maxilla and mandible models with and without resin markers. Methods: A pair of standard edentulous models were scanned using a laboratory scanner and saved as reference models. The edentulous models were fixed onto a phantom head and scanned with an intraoral scanner (IOS) five times each. Six resin markers were attached on the maxilla model and two on the mandible model, and another five intraoral scans were taken of each model. The scanning time and number of images were recorded. The digital models obtained using the IOS were superimposed on the reference models using image processing software. The trueness and precision of the models made using the IOS were evaluated, and the scanning time and number of images were also compared. Results: The average trueness and precision of the IOS in the maxilla model with resin markers were 135.50 ± 36.28 μm and 254.55 ± 40.62 μm, respectively, while those in the mandible were 161.40 ± 55.45 μm and 368.75 ± 91.03 μm, respectively. Placing resin markers on the edentulous maxilla and mandible did not improve the trueness of the IOS, but placing resin markers on the edentulous maxilla improved the precision and scanning efficiency. However, placing resin markers on the buccal shelf of the edentulous mandible decreased the precision and increased the scanning time. Conclusion: Resin markers placed on the hard palate of edentulous maxillae could improve the precision of the IOS and improve scanning efficiency. However, they did not affect the trueness of the IOS for edentulous maxillae or mandibles.

Objective: To analyze changes in occlusal force distribution and occlusal contact in posterior partial fixed implant-supported prostheses over time, and to provide reference for the precise occlusion design, adjustment and maintenance of implant prostheses., Methods: According to certain inclusion and exclusion criteria, patients were recruited from partially edentulous patients who had received implant-supported single crown or fixed bridge in the posterior region. The patients were collected since the implant prostheses settling and scheduled for the routine examination of implant prostheses and the occlusal examinations of complete dentition after 2 weeks, 3, 6, and 12 months. Occlusal examinations were taken with the articulating papers and T-Scan III (Tekscan, South Boston, USA), which could check and measure the occlusal contact condition of complete dentition. The occlusion time and relative occlusal forces of implant prostheses, mesial adjacent teeth and control teeth were recorded at the same time., Results: Thirty-seven posterior partial fixed implant prostheses in 33 patients (17 women and 16 men, aged 24-70 years) were followed up for 3-12 months (average 8.3 months). At baseline, the relative occlusal forces of implant prostheses were significantly lower than those of the corresponding control teeth (P<0.001). However, after 3 months, the relative occlusal forces of implant prostheses had significantly increased (P<0.05), while control teeth decreased significantly (P<0.05), resulting in no statistical significance between them. The implant prostheses occlusion time ratio also increased significantly from 2 weeks to 3 months (P<0.05). There was no significant difference from the third month to the sixth month, or from the sixth month to the twelfth month (P>0.05)., Conclusion: Light contact and time-delayed occlusion of posterior implant prostheses changes significantly in the first three months after settling implant prostheses. These changes mainly include the advance of the time point of the implant prosthesis to start the occlusion contact, and the increase of the occlusal force of the implant prosthesis. The occlusion of posterior implant prostheses should be carefully monitored at end of the third month follow-up clinically.

Objective: Venous thromboembolism (VTE) is a common cardiovascular disease, in which pulmonary embolism (PE) is potentially life-threatening. Accurate biological markers for the early diagnosis of VTE are needed. The purpose of this study was to analyze and validate the predictive value of microRNAs for the diagnosis of VTE., Methods: A comprehensive literature review was conducted using the PubMed, Embase, and Cochrane Library databases and is current through Sep 27, 2018. The diagnostic value of microRNAs for VTE was analyzed by creating a summary receiver operating characteristic curve (SROC) and calculating the area under the curve (AUC)., Results: Our analysis included 12 articles assessing a total of 1057 individuals. The most frequently researched microRNA was miR-134, and the pooled results of the predictive ability of this miRNA with 95% confidence intervals (CIs) showed an average sensitivity of 0.82 (0.69-0.91) and an average specificity of 0.83 (0.68-0.92). The average AUC for the SROC curves was 0.89 (0.86-0.92). For other microRNAs, AUC values >0.8 were considered as potential diagnostic indices. These microRNAs included miR-1233, miR-134, miR-145, miR-483-3p, miR-582, miR-532, and miR-195., Conclusions: MicroRNAs may act as novel diagnostic biomarkers for VTE, and miR-1233, miR-134, miR-145, miR-483-3p, miR-582, miR-532, and miR-195 are prime candidates. Of these, research on miR-134 is the most extensive and reliable., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Occlusal splint is a removable device for the treatment of oral and maxillary diseases with reversible occlusal treatment property. When patients wear the occlusal splint, the occlusal contact state can be changed and the position of the lower jaw may be adjusted, with the improvement of functions of temporomandibular joints and masticatory muscles. There are various types of occlusal splints, among which stabilization splint, soft occlusal splint and repositioning splint are widely used in the treatment of temporomandibular disorders and night bruxism. For the patients requiring occlusal reconstruction, occlusal splint can be used as an important means to adjust and verify the therapeutic jaw position. As a major trend of research in future, the digital design and production of occlusal splint are still in the initial stage and need to be further improved.

The effects of thermal oxidation at 65 °C for 24 days on oxidation indices, fatty acid positional distribution, thermal properties, vitamin E composition and sterol composition of kenaf seed oil are investigated. The results showed that total oxidation value (TOTOX) of the oil increased from initial 8.83 to 130.74 at the end of 24 days storage. Linoleic acid at sn-1, 3 positon of kenaf seed oil was less stable than the one at sn-2 positon. Oxidative degradation changed the melting profile of kenaf seed oil, the value of endothermic enthalpy reduced from 58.17 to 20.25 J/g after 24 days of storage. Moreover, the content of vitamin E and total sterol decreased by 84.26% and 38.47%, respectively. Tocotrienols were more stable than tocopherols during the accelerated storage. Correlation analysis indicated vitamin E content was significantly related to p-anisidine value, while sterol content was significantly related to peroxide value. PRACTICAL APPLICATION: Kenaf seed oil is rich in polyunsaturated fatty acids and bioactive compounds. Heating process and long-term storage cause oil oxidation and bioactive compounds degradation. The oxidation process of kenaf seed oil is simulated with accelerated storage. The study evaluates fatty acid composition and distribution, vitamin E and sterol content, melting thermal characteristics of kenaf seed oil at different oxidation levels. The research shows the stability of fatty acid is related with its type and position in backbone of triacylglycerol molecule. There are good correlation among oxidation level, vitamin E and sterol content, and melting enthalpy value of kenaf seed oil., (© 2019 Institute of Food Technologists®.)

Background: Human leukocyte antigen (HLA) alleles are implicated in drug-induced hypersensitivity, including by nevirapine and abacavir. The purpose of this meta-analysis was to evaluate the relationship between HLA polymorphisms and hypersensitivity to antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients., Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library for studies that evaluated the associations of HLA polymorphisms with antiretroviral therapy-induced hypersensitivity published in April 2019. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were considered as estimates of the effect., Results: The meta-analysis included 17 studies that assessed a total of 4273 patients. First, carriers of HLA-A *24 were associated with an increased risk of hypersensitivity among patients with HIV who received antiretroviral therapy (OR: 12.12; P = 0.018). Second, five SNPs of HLA-B genotypes, including *18 (OR: 1.63; P = 0.028), *35 (OR: 2.31; P = 0.002), *39 (OR: 11.85; P = 0.040), *51 (OR: 1.66; P = 0.028), and *81 (OR: 8.11; P = 0.021), were associated with an increased risk of hypersensitivity. Conversely, carriers of HLA-B *15 were associated with a reduced risk of hypersensitivity (OR: 0.43; P < 0.001). Third, HLA-C *04 was associated with an increased risk of hypersensitivity (OR: 3.09; P < 0.001), whereas a lower risk for hypersensitivity was observed in patients who were carriers of HLA-C *02 (OR: 0.22; P = 0.030), *03 (OR: 0.53; P = 0.049), and *07 (OR: 0.61; P = 0.044). Finally, carriers of HLA-DRB1 *05 (OR: 0.18; P = 0.006) and *15 (OR: 0.23; P = 0.013) were associated with a reduced risk of hypersensitivity among patients receiving antiretroviral therapy., Conclusions: The findings of this meta-analysis indicated patients carrying HLA-A *24, HLA-B *18, *35, *39, *51, *81, HLA-C *04 were associated with a higher risk of hypersensitivity. Conversely, subjects carrying HLA-B *15, HLA-C *02, *03, *07, HLA-DRB1 *05, *15 were associated with a reduced risk of hypersensitivity.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS). The present study explored the role of intestinal microbiota in the initiation and propagation of mice induced by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 48 C57BL/6 were randomly divided into control group and EAE group. The changes of body weight and the scores of neurological function were recorded. The mRNA expression of the receptor tyrosine kinase subfamily (AXL) was detected by real-time quantitative PCR. The levels of IL-17 and IFN-γ in blood samples were examined by ELISA. The intestinal microbial composition of mice at different time points during the EAE induction was analyzed by 16S rRNA gene-based sequencing. In EAE group, the body weight began to reduce at day 3 and neurological symptoms began to appear at day 7 after EAE induction. The levels of IL-17 and IFN-γ in EAE group reached the peak at day 21 and then decreased gradually. However, the expression of Axl and SOCS3 reached the lowest level at day 21 and then increased gradually. The microbiome analyses revealed that the abundances of Alistipes, Blautia , and Lachnospiraceae &#95;NK4A136&#95;group were significantly changed at day 14, whereas the abundances of Allobaculum, Eubacterium and Helicobacter were significantly changed at day 30 of EAE induction. The prevotellaceae&#95;NK3B31&#95;group may be key bacteria that contribute to the development of MS. Regulation of intestinal microbiota composition can become a new therapeutic target for the treatment of MS., (© 2019 The Author(s).)

Aims: To compare somatosensory function profiles and psychologic factors in patients with primary burning mouth syndrome (BMS) and healthy controls and to evaluate correlations of subjective pain ratings with somatosensory and psychologic parameters., Methods: A quantitative sensory testing (QST) protocol-including cold detection threshold (CDT), warmth detection threshold (WDT), thermal sensory limen (TSL), paradoxical heat sensation (PHS), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR), and pressure pain threshold (PPT)-was performed at the oral mucosa of the tongue, buccal, and palatal sites in 30 Chinese patients (25 women and 5 men, mean age 50.9 ± 9.2 years) with primary BMS and in 18 age- and gender-matched healthy controls (15 women and 3 men, mean age 53.2 ± 7.0 years). For each BMS patient, z scores and loss/gain scores were computed. Psychologic status was evaluated in both groups using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Correlations of BMS patients' subjective pain ratings with somatosensory and psychologic profiles were assessed with the use of Pearson or Spearman correlations and multiple linear regression., Results: In BMS patients, 53.3% had somatosensory abnormalities according to z scores vs 22.2% of healthy controls (P = .033). The abnormalities in BMS patients were somatosensory loss to thermal nonnoxious stimuli (TSL = 20.0%, CDT = 13.3%, WDT = 13.3%), mechanical pressure stimuli (PPT = 16.7%), pinprick stimuli (MPT = 6.7%), and thermal pain stimuli (CPT = 3.3%), and somatosensory gain to repetitive pinprick stimuli (WUR = 6.7%), pressure stimuli (PPT = 6.7%), and thermal pain stimuli (HPT = 3.3%). The most frequent loss/gain score was 13.3% for loss of thermal somatosensory function with no somatosensory gain; 13.3% for loss of thermal and mechanical somatosensory function with no somatosensory gain; and 13.3% for gain of mechanical somatosensory function with no somatosensory loss. Mild elevations in anxiety scores were seen in 30% of the BMS patients, and 50% and 36.7% had mild and moderate elevations, respectively, in depression scores. No anxiety or depression was detected in the control group. QST results, but not psychologic scores, were significantly correlated with patients' subjective pain ratings (PHS, Spearman coefficient -0.384, P = .029; CPT, Pearson coefficient -0.370, P = .034; MPT, Pearson coefficient -0.376, P = .032; PPT, Pearson coefficient 0.363, P = .037)., Conclusion: The present findings documented distinct differences in somatosensory function in patients with primary BMS compared to controls, indicating a complex pathophysiology and interaction between impairments in nociceptive processing and psychologic functioning.

Acute occlusal interference following improper occlusal alteration in dental practice can induce chronic masticatory muscle pain. The underlying mechanism has not been clarified. Synaptic plasticity in the anterior cingulate cortex (ACC) plays a key role in the chronic pain state. This study investigated the role of synaptic plasticity in the ACC in acute occlusal interference-induced chronic masticatory muscle pain. A rat model of experimental occlusal interference (EOI) was established. In vivo local field potential (LFP) recording was conducted to evaluate the change of synaptic strength and plasticity from the medial thalamus (MT) to the ACC after EOI application. The effects of microdialysis of antagonists of glutamate receptors into the ACC on synaptic transmission from the MT to the ACC were examined. Furthermore, the influence of inhibiting glutamate receptors in the ACC on EOI-induced mechanical hyperalgesia in the masseter muscles of rats was investigated. The amplitude of LFP in the ACC evoked by MT stimulation was significantly potentiated since 14 d of EOI application. Long-term potentiation of LFP in the ACC was reliably induced by theta burst stimulation to the MT in control rats but was occluded in 14-d EOI rats. Microdialysis of AMPA/kainate receptor antagonist CNQX into the ACC attenuated LFP in the ACC evoked by stimulating the MT in control and EOI rats. Administration of NMDA receptor subunit NR2B antagonist Ro 25-6981 into the ACC significantly alleviated the potentiation of MT stimulation-evoked LFP in the ACC of EOI rats without affecting that in control rats. EOI-induced hyperalgesia in the bilateral masseter muscles of rats was dose-dependently relieved after microdialysis of Ro 25-6981 into ACC. These findings provide direct evidence that prolonged acute occlusal interference potentiates synaptic transmission in the ACC, which in turn mediates chronic masticatory muscle pain.

Objective: To investigate the effect of long-term resistance exercise of hindlimb on mechanical hyperalgesia of bilateral masseter muscle in rats with or without occlusal interference., Methods: Six-teen male Sprague-Dawley rats (220-250 g) were randomly divided into four groups: the naive control group, naive exercise group, occlusal interference control group, and occlusal interference exercise group. The rats in occlusal interference groups (occlusal interference control group and occlusal interference exercise group) obtained occlusal interference with 0.4 mm-thick crowns bonded to the right maxillary first molars. The rats in exercise groups (naive exercise group and occlusal interference exercise group) performed squat-type resistance exercises for 30 minutes, once a day, 5 days/week, lasting for 14 weeks. Resistance exercise was recorded every day. Mechanical withdrawal thresholds of bilateral masseter muscle were tested per week by use of modified electronic von-frey anesthesiometer. The rats were weighed per week. After the 14-week exercise, the muscle strength of the hindlimb was tested with a grip strength meter. Muscle (gastrocnemius and soleus) weight of bilateral hindlimb and length of bilateral fibula of the rats were obtained. The muscle-mass/body-mass ratios and muscle-mass/fibula-length ratios were calculated., Results: Between the naive control group and naive exercise group, there was no significant difference in the mechanical withdrawal thresholds of bilateral masseter muscle for the 0-4 weeks (P>0.05). During the 5-14 weeks, the mechanical withdrawal thresholds of the rats in the naive exercise group were higher than those in the naive control group (P<0.05). Between the occlusal interference control group and occlusal interference exercise group, there was no significant difference in the mechanical withdrawal thresholds of bilateral masseter muscle for the 0-6 weeks (P>0.05). During the 7-14 weeks, the mechanical withdrawal thresholds of rats in the naive exercise group were higher than those in the occlusal interference control group (P<0.05). After the 14week exercise, the body mass of the rats in nonexercise group (the naive control group and occlusal interference control group) were larger than those in exercise group [(462±6) g vs. (418±14) g, P<0.05]. And the muscle strength of hindlimb of the rats in exercise group were bigger than those in non-exercise group [(6.75±0.13) N vs. (5.41±0.15) N, P<0.01]., Conclusion: long-term resistance exercise can increase mechanical withdrawal thresholds of the bilateral masseter muscle in rats with or without masseter muscle mechanical hyperalgesia.

Numerous studies have illustrated the relationship between SLCO1B1 T521C polymorphism and statin-induced myopathy risk; however, this association is not consistent. Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from inception to October 2017 to identify potential studies. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from different genetic models by using a random-effects model. Fourteen studies comprising 3265 myopathy patients and 7743 controls were included. The summary ORs suggested that 521CC (OR: 2.31; 95% CI: 1.15-4.63; P = 0.019), 521TC (OR: 1.34; 95% CI: 1.02-1.76; P = 0.034), and 521CC + TC (OR: 1.82; 95% CI: 1.32-2.51; P < 0.001) were associated with a greater risk of statin-induced myopathy than 521TT. The higher incidence of statin-induced myopathy was found to be significantly correlated with the C allele compared with the T allele (OR: 1.89; 95% CI: 1.36-2.62; P < 0.001). In addition, we observed that 521CC + TC was associated with an increased risk of myopathy in individuals who received simvastatin (OR: 2.35; 95% CI: 1.08-5.12; P = 0.032) or rosuvastatin (OR: 1.69; 95% CI: 1.07-2.67; P = 0.024) when compared with 521TT. The 521C allele was associated with a greater risk of cerivastatin-induced myopathy than the T allele (OR: 1.95; 95% CI: 1.47-2.57; P < 0.001). The findings of this study indicated that SLCO1B1 T521C was associated with a significantly higher risk of statin-induced myopathy, especially for simvastatin, rosuvastatin, and cerivastatin. Future studies should be conducted in subjects receiving specific types of drugs, and any potential adverse events need to be explored.

Fungal infection is inevitable in the cultivation and storage process of soybean. Gamma irradiation is an effective method to control fungal growth and inactivate mycotoxins. The effects of gamma irradiation and fungal damage on the number of fungi, aflatoxin B 1 content, proximate composition of soybeans, and quality of soybean oil (acid value, peroxide value, iodine value, fatty acid profile, tocopherols content, and oxidation stability) were investigated in this work. Growth of fungi caused some changes in proximate composition of soybean and qualities of soybean oil. However, the changes depended on the damage extent of soybeans. No significant change was found for the soybeans incubated for 30 days (moderately fungi-damaged). Gamma irradiation could completely eliminate the fungi and greatly reduce the content of aflatoxin B 1 in soybeans at 10 kGy. For soybeans incubated for 30 days, there were no significant changes in the quality attributes, tocopherols content and oxidation stability of oil when the gamma irradiation dose was less than 20 kGy. Gamma irradiation is a promising method to improve the safety and economy of moderately fungi-damaged soybean used for feedstuff., (Copyright © 2018 Elsevier Ltd. All rights reserved.)