Mandible-First Sequencing Increase Surgical Accuracy for Patients With Skeletal Class II Malocclusion Concomitant With Unstable Condyle-Fossa Relation.

The aim of this study was to explore whether mandible-first sequencing increases the surgical accuracy in bimaxillary orthognathic surgery for patients with skeletal class II malocclusion concomitant with the unstable condyle-fossa relation. A retrospective evaluation of 19 patients who had undergone virtually planned double-splint orthognathic surgery with different operation sequences was performed: maxilla-first (n=9) or mandible-first (n=10) surgery. The centroid position, translational, and rotational differences in the maxilla were evaluated by comparing the virtual plans with actual results. The stability was assessed by comparing the actual results with the follow-up outcomes 6 months postoperatively. The accuracy of the maxilla centroid position was improved in mandible-first sequencing surgery: mandible-first 1.87±0.94 mm versus maxilla-first 2.70±0.75 mm (P<0.05). Moreover, no significant difference was detected in the translational and orientational discrepancies between the 2 groups. Neither sequencing procedure differed in the overall stability: maxilla-first (1.48±1.13 mm) versus mandible-first (1.57±0.90 mm). This study indicated that the mandible-first surgery leads to a more accurate maxilla position than the maxilla-first surgery for patients with skeletal class II malocclusion concomitant with the unstable condyle-fossa relation.

The Effects of Social Status and Imposition on the Comprehension of Refusals in Chinese: An ERP Study.

This study aims to examine how real-time processing of information about the social status of interlocutors (high vs. low) and the imposition of making a refusal by manipulating the indirectness of invitation forms (declining direct invitations vs. declining indirect invitations) affects the interpretation of refusals in Chinese. The event-related potentials results showed that high-status invitees who decline invitations from low-status inviters elicited weaker N400 effects followed by late mitigated negative effects, while high imposition refusals elicited stronger N400 effects followed by increased late negativities. The two factors of social status and imposition functioned independently during the comprehension of refusal utterances. These findings suggest that individuals take the social status of interlocutors and the imposition of making a refusal into consideration as an utterance unfolds, while face-threatening contexts create inferential difficulties for reinterpreting the pragmatic implications of an utterance.

Evaluation of Related Factors of Maxillary Sinusitis After Le Fort I Osteotomy Based on Computed Tomography: A Retrospective Case-Control Study.

ABSTRACT: Maxillary sinusitis is 1 of the postoperative complications of the Le Fort I osteotomy, this study investigated the related factors of maxillary sinusitis after Le Fort I osteotomy. A total of 23 cases, 92 controls, and 11 related factors were included in this case-control study with a 1:4 case-control ratio. The risk factors for maxillary sinusitis after Le Fort I were examined by least absolute shrinkage and selection operator multivariate conditional logistic regression and least absolute shrinkage and selection operator multivariate linear regression. The patency of maxillary sinus ostium at 6 months after surgery was significantly associated with maxillary sinusitis after Le Fort I osteotomy. Compared with the obstructed maxillary sinus ostium, the percentage of the volume of the healthy air cavity in the complete sinus cavity increased 70.7% when the maxillary sinus ostium was unobstructed, and 95% confidence interval was 0.610 to 0.805. Similarly, when the maxillary sinus ostium was wide, the percentage increased 6.0% compared with the narrow 1, and 95% confidence interval was 0.013 to 0.107. This study indicated that the patency of maxillary sinus ostium has an important impact on maxillary sinusitis after Le Fort I osteotomy. Close attention should be paid to maintain the maxillary sinus ostium and the drainage of maxillary sinuses unobstructed in a clinical setting.

Prediction of 3-month treatment outcome of IgG4-DS based on BP artificial neural network.

OBJECTIVE: The study aimed to establish an effective back-Propagation artificial neural network (BP-ANN) model for automatic prediction of 3-month treatment outcome of IgG4-DS. METHODS: A total of 26 IgG4-DS patients at Shanghai Ninth People's Hospital from January 2018 to December 2019 were involved in the study. They were all followed for >3 months. The primary outcome was reduction of serum IgG4 (sIgG4) after 3-month treatment. The association between risk factors and reduction of sIgG4 was analyzed by Spearman's rank correlation test. According to the R values, we built a BP-ANN model by MATLAB R2019b. RESULTS: The average reduction of sIgG4 was 5.55 ± 5.03. After Spearman's rank correlation test, ESR, sIgG4, and sIgG were independently associated with reduction of sIgG4 (p < .05) and were selected as input variables. Take into account these parameters, BP-ANN model was developed and the coefficient of determination (R2 ) model was 0.95512. CONCLUSION: The BP-ANN model based on ESR, sIgG4, and sIgG could predict the 3-month reduction of sIgG4 for IgG4-DS patients. It showed potential clinical application value.

Effects of autologous concentrated growth factor on gingival thickness in periodontal accelerated osteogenic orthodontics: a 6-month randomized controlled trial.

BACKGROUND: Earlier studies have not given clear results of concentrated growth factor (CGF) on gingival thickness (GT) in periodontal accelerated osteogenic orthodontics (PAOO). This randomized controlled trial aimed to evaluate the effects of CGF on GT in patients with thin gingival phenotype undergoing PAOO. METHODS: Forty four patients presenting 264 anterior mandibular teeth were recruited and randomly allocated to one of the groups: test-positioning of autologous CGF after PAOO or control-positioning of a collagen membrane after PAOO. GT, gingival height (GH), buccal alveolar bone thickness (BT), and buccal alveolar bone height (BH) were evaluated depending on cross-sectional CBCT images at t0 (before surgery) and t1(6 months after surgery). RESULTS: GT were increased in both groups at t1 compared to t0. Yet, higher values were observed in the test group (from 0.94 ± 0.23 to 1.31 ± 0.33 mm) compared to the control group (from 0.94 ± 0.19 to 1.02 ± 0.16 mm) (p < 0.05). Moreover, in the intergroup comparison, GT at t1 in the test group was significantly higher compared to the control group (p < 0.01). Furthermore, the GT of central incisors, lateral incisors and canine teeth all showed significantly changes compared with baseline and the test group showed higher increase (p < 0.01). No statistically significant difference were found in GH, BT, BH and all clinical parameters between two groups at t1 (p > 0.05). CONCLUSIONS: Within the limitation of this study, gingival thickness could be increased by using CGF in PAOO for the patients with thin gingival phenotype. Trial registration The study was registered in Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ) under the number ChiCTRINR17013346, Registered 11 November 2017.

Toll-like receptor 9 signaling promotes autophagy and apoptosis via divergent functions of the p38/JNK pathway in human salivary gland cells.

Abnormal signaling transduction in salivary gland cells is associated with the pathogenesis of Sjögren's syndrome (SS). Previously, we identified aberrant expression of toll-like receptor 9 (TLR9) in gland cells of SS patients and mouse models. In this study, we investigated the role of TLR9 and its downstream p38/mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) signaling in mediating apoptosis and autophagy in human salivary gland (HSG) cells. We selected either CpG-Odn, a classical TLR9 activator, or lentivirus-packaged TLR9 full-length cDNA to activate TLR9 signaling transduction. Activation of TLR9 signaling induced phosphorylation of its downstream protein kinases, p38/MAPK and JNK, in a time-dependent manner, and decreased HSG cell viability. Western blotting of LC3B-II and p62 in both normal and autophagic flux-administered conditions revealed elevated autophagy upon TLR9 activation. Observing the cell cytoplasm through transmission electron microscopy and mRFP-GFP-LC3B-tagged fluorescence confirmed an increased number of autophagosomes and autolysosomes in TLR9-activated cells. Bax/Bcl-2 ratio calculations, caspase-3 activity assays and Hoechst nuclear staining were utilized to confirm the involvement of apoptosis in TLR9 signaling activation. Furthermore, we selected SB239063, a p38/MAPK signaling inhibitor, and SP600125, a JNK inhibitor, to identify the functions of p38/MAPK and JNK in TLR9-mediated signaling transduction. Multiple approaches, including Western blotting assays, fluorescence assessments and caspase-3 activity measurements, confirmed that inhibition of p38/MAPK signaling ameliorated both autophagy and apoptosis in TLR9-activated HSG cells, whereas inhibition of JNK signaling attenuated apoptosis but failed to modulate autophagy in the models mentioned above. Our results indicate a divergent function of p38/MAPK and JNK in TLR9-mediated autophagy and apoptosis in salivary gland cells.

Association between periodontal disease and tooth loss and mortality in an elderly Chinese population.

BACKGROUND: Poor oral health is a risk indicator of poor quality of life and mortality. However, whether these associations remain potent in elderly subjects after adequately considering the confounding factors is not yet clearly elucidated. The present study aimed to investigate the associations between periodontal disease and tooth loss and total mortality and cardiovascular disease (CVD) outcomes in the elderly > 75 years old. METHODS: A total of 1385 individuals, receiving periodontal treatment in Shanghai, participated in this retrospective study. Data on oral status were obtained from radiographs to calculate the proportion of residual bone. The information about mortality was collected from the Shanghai Municipal Center for Disease Control and Prevention (SCDC). Univariate Cox proportional hazards model, multivariable-adjusted model, and competing risk hazard model were used to analyze the association between periodontal disease or tooth loss and mortality. RESULTS: Those with severe periodontitis were associated with higher risk of total mortality than healthy individuals [hazard ratio (HR) = 1.48, 95% confidence interval (95% CI) 1.11-1.98]. Further, missing teeth increased the risk of total mortality (HR = 1.02, 95% CI 1.01-1.03). However, no significant difference was detected in the association between periodontitis or tooth loss and CVD mortality. In competing risk hazard model, an increased risk was observed for other-cause mortality, not CVD mortality, in those with severe periodontitis and missing teeth. CONCLUSION: Periodontal diseases and tooth loss were the potential predictors of total mortality even after adjustment for confounding factors. However, these were not independent indicators for CVD mortality.

[Expression of TWEAK and Its Receptor CD163 in Peripheral Blood of Psoriasis Vulgaris (PV)].

OBJECTIVE: To investigate serum levels and mRNA expressions of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor CD163 from the patients with psoriasis vulgaris (PV). METHODS: Peripheral blood samples were obtained from 28 patients with PV and 15 healthy control subjects. Serum levels of TWEAK and CD163 were detected by ELISA, mRNA expressions of TWEAK and CD163 in peripheral blood were analyzed by real time-PCR, and protein expressions of TWEAK and CD163 were determined by flow cytometry. RESULTS: All the 28 PV patients were in progressive stage at the beginning of this study, 10 patients then recovered in convalescent stage after treatment. Compared to healthy controls, PV patients had higher serum TWEAK levels and lower serum CD163 levels. Serum TWEAK level in progressive stage was significantly higher than that in convalescent stage. Serum CD163 level were elevated significantly in convalescent stage compared with those in progressive stage. TWEAK mRNA expression in PV patients were significantly lower than that in healthy controls, but there was no significant differences of CD163 mRNA expression. TWEAK expression in monocytes in progressive stage and convalescent stage were significantly higher than that of controls, CD163 expression in monocytes in progressive stage and convalescent stage significantly lower than that in controls. No correlations wene found between psoriasis area and severity index (PASI) score and expression of TWEAK and CD163. CONCLUSION: TWEAK/CD163 pathway may play a role in PV.

Network pharmacology and experimental verification to explore the anti-superficial thrombophlebitis mechanism of Mailuo shutong pill.

ETHNOPHARMACOLOGICAL RELEVANCE: Mailuo shutong pill (MLST) has been widely used in clinical treatment of superficial thrombotic phlebitis (STP). Nevertheless, the major active components of MLST and the mechanism of synergistic action have not been reported. AIM OF THE STUDY: The present study aimed to evaluate the improving effects and the underlying mechanism of MLST on mannitol-induced STP in rabbits. MATERIAL AND METHODS: In this study, Ultrahigh-performance liquid chromatography electrospray ionization quadrupole-exactive orbitrap mass spectrometry (UHPLC-ESI-Q-Exactive-Orbitrap-MS) was used to analyze and identify the chemical composition of MLST and the prototype components absorbed into the blood. Then, according to the prototype components in serum, the targets and mechanisms of MLST were explored by applying network pharmacology. The rabbit model of STP was established by injecting 20% mannitol into bilateral auricular vein. The pathological changes of rabbit ear tissues, inflammatory factors, coagulation function and hemorheology were detected. In addition, molecular docking verified the interaction between the main active ingredient and the key target. Finally, the PI3K/AKT pathway and its regulated downstream pathways were verified by Western blot. RESULTS: A total of 96 MLST components and 53 prototypical components absorbed into the blood were successfully identified. Based on network pharmacology, PI3K/AKT pathway and 10 chemical components closely related to this pathway were obtained. Hematoxylin-eosin (HE) staining results indicated that MLST effectively improved of the pathological damage of ear tissues. MLST decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and C-reactive protein (CRP). The expression of platelets (PLT) and fibrinogen concentration (FIB) was decreased, while prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged. In addition, the plasma viscosity and whole blood viscosity in the MLST groups were significantly decreased. The more important discovery was that the expressions of P-PI3K, VEGF, P-AKT, P-IκB-α, P-NF-κB, NLRP3, ASC, Cleaved IL-1ß and Cleaved Caspase-1 were effectively reversed after treatment with MLST. CONCLUSIONS: This study comprehensively analyzed and characterized the chemical composition of MLST and the prototypical components absorbed into the blood. This study strongly confirmed the pharmacodynamic effect of MLST on STP. More importantly, this pharmacodynamic effect was achieved through inhibition of the PI3K/AKT pathway and its regulated NF-κB and NLRP3 pathways.

Pharmacokinetics, tissue distribution and excretion of six bioactive components from total glucosides picrorhizae rhizoma, as simultaneous determined by a UHPLC-MS/MS method.

Total glucosides picrorhizae rhizome (TGPR) is an innovative traditional Chinese medicine, which is a candidate drug for the treatment of nonalcoholic steatohepatitis (NASH). However, there is still lack of deep research on the behaviors of TGPR in vivo. In this study, a reliable, specific, and sensitive liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been constructed for simultaneous determination of picroside I, picroside II, vanillic acid, androsin, cinnamic acid and picroside IV, the major active constituents of TGPR, in rat various biological matrices (plasma, tissue, bile, urine and feces) using diphenhydramine hydrochloride and paeoniflorin as the internal standard. All biosamples were prepared using a simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a waters UHPLC® HSS T3 (100×2.1 mm, 1.8 µm) column. The mobile phase consisted of methanol: acetonitrile1(1:1, V/V) and 0.5 mM ammonium formate in water, was employed to separate six components from endogenous interferences. The components were detected with a triple quadrupole mass spectrometer using positive and negative ion multiple reaction monitoring (MRM) mode. The newly developed method was successfully applied to investigate the pharmacokinetics, tissue distribution and excretion of six components in rats. The pharmacokinetic results indicated that the six components in TGPR could be quickly absorbed and slowly eliminated and their bioavailability were less than 12.37%, which implied the poor absorption after intragastric dosing. For tissue distribution, the six components in TGPR were detected in liver and only androsin could penetrate the blood-brain barrier. Meanwhile, the excretion study demonstrated that vanillic acid was mostly excreted as prototype drugs and the remaining five components might be widely metabolized in vivo as the metabolites, the unconverted form was excreted mainly by feces route. The pharmacokinetics, tissue distribution and excretion characteristics of six bioactive components in TGPR were firstly revealed, which will provide references for further clinical application of TGPR as an anti-NASH drug.

Intestinal flora, intestinal metabolism, and intestinal immunity changes in complete Freud's adjuvant-rheumatoid arthritis C57BL/6 mice.

Rheumatoid arthritis (RA) is an inflammatory-mediated autoimmune disease characterized by persistent joint enlargement, synovial cartilage damage, and inflammatory infiltrates. Although the pathogenesis and treatment of RA are still currently insufficient, the importance of the intestine flora, metabolism and immunity for RA has been gradually recognized, and many intestine regulatory strategies have been used to treat RA. However, the relationship between RA and intestine flora, metabolism and immunity has not been fully expounded. In this study, Complete Freund's Adjuvant (CFA) was used to establish RA model, CyTOF technology was used to study the changes of intestinal immune cell types, 16S rRNA technology was used to analyze the differences of intestinal flora, and LC-MS technology was used to explain the effects of metabolites produced by the changed intestinal flora on RA. Moreover, we systematically explored how the imbalance of intestinal flora changed the intestinal immune status through its metabolites in RA mice. Our results showed that the intestinal flora of RA mice changed significantly, and the bacteria producing short-chain fatty acids (SCFAs), indole classes and secondary bile acids were significantly reduced. The abundance of SCFAs, indole classes and secondary bile acids in the intestine were significantly decreased. The balance of immune cells in the intestine of RA mice was significantly disrupted, with an overall decrease in immune cells. This work reveals the possible relationship between intestinal flora, metabolism and immunity and RA in mice, which will provide new therapeutic strategies for RA.

Jingfang granules ameliorate inflammation and immune disorders in mice exposed to low temperature and high humidity by restoring the dysregulation of gut microbiota and fecal metabolites.

The dramatic changes in global climate on human health have been extremely severe. The immune disorder caused by low temperature and high humidity (LTHH) have become a severe public health issue. Clinically, Jingfang granule (JF) has the effect of dispelling cold and eliminating dampness, and is widely used in the treatment of cold caused by wind and cold, autoimmune diseases, and COVID-19 with cold-dampness stagnating in the lung pattern. Our study aims to elucidate the effect of JF on LTHH-induced immune disorders in mice as well as the underlying mechanisms. In this study, JF increased the spleen index, improved fecal character, repaired the intestinal barrier and alleviated intestinal inflammatory responses. Most importantly, JF ameliorated immune disorder in LTHH mice, which was manifested primarily by the significant increase in gdT, CD8+ Tcm, and CD8+ Tem cells, as well as the decrease in TH1, TH17, CD4+ Tem1, CD4+ Tem2, immature NK, mature NK cells, and M1-like macrophages. Interestingly, the JF treatment not only regulated the gut microbiota by decreasing the abundance of harmful bacteria, as well as up-regulating the abundance of beneficial bacteria, but also ameliorated the metabolic disorders by reversing the levels of fecal metabolites to normality. The results of the correlation analysis demonstrated a significant association among gut microbiota, fecal metabolites and immune cells. In addition, JF inhibited the TLR4/NF-κB/NLRP3 pathway in LTHH mice. In conclusion, our results suggested that JF alleviated inflammation and immune disorders in LTHH mice by restoring gut microbiota and fecal metabolism.

Conflicts influence affects: an FMRI study of emotional effects in a conflict task.

Although prior research has confirmed that conflict itself is likely to be aversive, it is unclear whether and how emotional conflicts influence an individual's affective processing. The current fMRI study adopted a lexical valence conflict task via instructing participants to shift lexical valence or not. We found that the involvement of positive emotions enhanced the activation of the middle right temporal gyrus (R-MTG) in the non-conflict condition, whereas such activation attenuated in the conflict condition. In addition, the R-MTG was activated in the opposite way when negative emotions were involved. The functional connectivity and correlation analyses further revealed that the faster the participants processed positive emotional words, the weaker the connectivity between R-MTG and positive emotion-related areas of left MTG in the non-conflict condition would be. In contrast, the faster the participants processed negative emotional words, the stronger the connectivity between R-MTG and negative emotion-related areas of the right cerebellum in the conflict condition would become. These findings suggest that conflicts have different influences on emotional processing.

Research progress of signaling pathways of the natural substances intervene dyslipidemia (Review).

Dyslipidemia is an umbrella term for a range of lipid metabolic disorders in the body. This condition has been widely reported to greatly increase the risk of cardiovascular diseases, threatening human health. In recent years, advances in molecular biology have deepened understanding of the dyslipidemia-related signaling pathways and specific mechanisms underlying dyslipidemia. Signaling pathways possess the ability to transmit an extracellular signal to the inside of the cell, leading to specific biological effects. Lipid metabolism disorders and lipid levels in the blood are frequently affected by aberrant alterations in the dyslipidemia-related signaling pathways. Therefore, further investigations into these pathways are required for the prevention and treatment of dyslipidemia. The present review summarizes the characteristics of six dyslipidemia-associated signaling pathways: Peroxisome proliferator-activated receptor, adenosine monophosphate-activated protein kinase, farnesoid X receptor, forkhead box O, adipocytokine and cyclic adenosine monophosphate signaling pathways. In particular, specific focus was placed on previous experimental studies and reports on the intervention effects of natural substances (compounds from animals, plants, marine organisms and microorganisms) on dyslipidemia.

Characterization of comprehensive dynamic epigenetic changes during human primary Sjögren's syndrome progression.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by reduced exocrine gland (principally the salivary and lacrimal glands) activity caused by chronic lymphocytic infiltration. Although pSS has been closely associated with an increased risk of mucosa-associated lymphoid tissue (MALT) lymphoma, the dynamic epigenetic changes in the gland cells that accompany the pathogenesis are not entirely understood. METHODS: In this study, we harvested tissue samples from the labial gland with (LG_pSS) or without pSS (LG_NC) before MALT development, as well as the parotid gland with tumor tissues (PG_MALT) and paracancerous tissues (PG_NC) of two pSS patients with MALT lymphoma, and conducted RNA-seq and ChIP-seq for tri-methylated histone 3 lysine 4, 9, 27, 36, and 79 (H3K4/9/27/36/79me3). RESULTS: Transcriptome landscapes indicated two outcomes of pSS progression with or without MALT lymphoma represented by distinct populations of differentially expressed genes and their functions. Furthermore, the epigenetic atlas of genome-wide H3K4/9/27/36/79me3 was in different stages for various samples, indicating that the variance of H3K4me3 was the earliest event, followed by selective alterations of H3K9/27/36/79me3. These four epigenetic modifications determine the final outcome of pSS progression. CONCLUSIONS: Our results not only advance the understanding of the dynamics of pSS progression and highlight the importance of epigenetic alterations in regulating transcription during this pathological process, but also identify potential therapeutic targets for pSS treatment and lymphoma intervention.

The value of inflammatory factors and red blood cell immune indices in predicting perinatal infection in hypertensive women after cesarean section.

OBJECTIVE: This study was conducted to explore the predictive value of inflammatory factors and red blood cell (RBC) immune indices in perinatal infection of women with pregnancy-induced hypertension after cesarean section. METHODS: Eighty women with pregnancy-induced hypertension and perinatal infection after cesarean section were enrolled as the study group. Another 80 pregnant women with hypertension but without perinatal infection during cesarean section were included as the control group. The two groups were compared in terms of interleukin-1ß (IL-1ß), IL-6, IL-10, transformation growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ), immune adhesion inhibitor (FEIR), immune adhesion promotion factor (FEER), and immune complex rosette (RBC-ICR) levels. The mothers in the study group were grouped according to the level of white blood cells, and the differences in related indicators of women in different inflammatory states were compared. Finally, the correlation between inflammatory factors and RBC-related immune indices was calculated. The differences in inflammatory factors and RBC-related immune indices were evaluated among different infection types. The ROC curve of IL-1ß, IL-6, IL-10 and FEIR, FEER, RBC-ICR for infection prediction was plotted. RESULTS: The study group showed significantly higher maternal levels of inflammatory factors and FEIR and lower FEER and RBC-ICR than the control group (P<0.05). There was a significant correlation between inflammatory factors and RBC-related immune indices (P<0.05), and there was little difference in inflammatory factors and RBC-related immune indices among different infection types (P>0.05). Inflammatory factors and RBC-related immune indices exhibited good predictive value for perinatal infection of women with pregnancy-induced hypertension. CONCLUSION: Prior to perinatal infection, the inflammatory factors and the RBC indices of women with hypertension and cesarean section are significantly altered. Monitoring these indicators can be used to evaluate maternal prognosis.

A new method for individual condylar osteotomy and repositioning guides used in patients with severe deformity secondary to condylar osteochondroma.

BACKGROUND: Mandibular condylar osteochondroma (OC) could lead to facial morphologic and functional disturbances, such as facial asymmetry, malocclusion, and temporomandibular joint dysfunction. However, after condylar OC resection, the inaccurate reposition of the neocondyle still needs to be solved. The purpose of this study was to explore the feasibility of the condylar osteotomy and repositioning guide to reposition the neocondyle in the treatment of patients with severe deformity secondary to condylar OC. RESULTS: Three patients with severe deformity secondary to OC of the mandibular condyle were enrolled in this study. With the aid of condylar osteotomy and repositioning guide, condylar OC resection and repositioning were carried out, and the accuracy and stability of these guides were evaluated. All patients healed uneventfully, and no facial nerve injury and condylar ankylosis occurred. Compared with the computerized tomography scans in centric relation before surgery and 3 days after surgery, the results showed that the facial symmetry was greatly improved in all the patients. Also, after the superimposition of the condylar segments before surgery and 3 days after surgery, the postoperative reconstructed condyles had a high degree of similarity to the reconstruction of the virtual surgical planning. Observed from the sagittal and coronal directions, the measurements of condylar positions were very close to those of virtual surgical planning. Moreover, it also showed stable results after a 1-year follow-up. CONCLUSIONS: For patients with severe deformity secondary to condylar OC, condylar osteotomy, and repositioning guide was expected to provide a new option for the improvement of facial symmetry and occlusal relationship.

The Interplay Between Language Form and Concept During Language Switching: A Behavioral Investigation.

Language switching involves multiple processing stages. Previous studies have not dissociated the cognitive process underlying language form switches and concept switches. Here, we examined the two factors using a novel language-switching paradigm. Chinese-English bilinguals named individually presented pictures in either Chinese or English according to a language cue. Pictures in two consecutive trials represented either identical, semantically related, or unrelated concepts. Results showed both language (form) switch costs and concept switch costs. The interaction between these two factors suggested that the effects were additive, with the longest naming response times observed when two pictures were semantically unrelated and involved a switch between languages. These findings suggest that the functional loci of the language control mechanism occur at multiple processing stages. Implications of the findings are discussed within current models of language processing in bilinguals.

Concentrated growth factor promotes gingival regeneration through the AKT/Wnt/ß-catenin and YAP signaling pathways.

Although concentrated growth factor (CGF) is known to promote gingival regeneration and improve the outcomes of clinical treatment, the mechanisms underlying its effects remain unknown. Therefore, this study aimed to elucidate the effects of CGF on gingival thickening. To this end, gingival mesenchymal stem cells (GMSCs) were treated with different concentrations of CGF, and the effects of CGF on cell proliferation and migration; collagen-1 (Col-1), fibronectin (FN), vascular endothelial growth factor (VEGF), and angiopoietin-1 (Ang-1) expression; and the AKT, Wnt/ß-catenin, and Yes-associated protein (YAP) signalling pathways were investigated. The effects of CGF in vivo were also investigated in a rat buccal gingival injection model. GMSCs cultured with CGF showed improved cell proliferation and migration. Moreover, CGF treatment improved the levels of FN, Col-1, VEGF, and ANG-1. These effects of CGF were mediated by the AKT/Wnt and YAP pathways, with the AKT pathway possibly functioning upstream of the Wnt/ß-catenin and YAP pathways. YAP was also shown to be overexpressed in the in vivo model. Thus, CGF can promote gingival regeneration, and YAP transport into the nucleus may be a key factor underlying this activity, which provides a novel perspective for gingival regeneration and further promotion of the clinical application of CGF.

An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression.

Objectives: To evaluate the pharmacodynamical effects and pharmacological mechanism of Ginsenoside H dripping pills (GH) in chronic unpredictable mild stress (CUMS) model rats. Methods: First, the CUMS-induced rat model was established to assess the anti-depressant effects of GH (28, 56, and 112 mg/kg) by the changes of the behavioral indexes (sucrose preference, crossing score, rearing score) and biochemical indexes (serotonin, dopamine, norepinephrine) in Hippocampus. Then, the components of GH were identified by ultra-performance liquid chromatography-iron trap-time of flight-mass spectrometry (UPLC/IT-TOF MS). After network pharmacology analysis, the active ingredients of GH were further screened out based on OB and DL, and the PPI network of putative targets of active ingredients of GH and depression candidate targets was established based on STRING database. The PPI network was analyzed topologically to obtain key targets, so as to predict the potential pharmacological mechanism of GH acting on depression. Finally, some major target proteins involved in the predictive signaling pathway were validated experimentally. Results: The establishment of CUMS depression model was successful and GH has antidepressant effects, and the middle dose of GH (56 mg/kg) showed the best inhibitory effects on rats with depressant-like behavior induced by CUMS. Twenty-eight chemical components of GH were identified by UPLC/IT-TOF MS. Subsequently, 20(S)-ginsenoside Rh2 was selected as active ingredient and the PPI network of the 43 putative targets of 20(S)-ginsenoside Rh2 containing in GH and the 230 depression candidate targets, was established based on STRING database, and 47 major targets were extracted. Further network pharmacological analysis indicated that the cAMP signaling pathway may be potential pharmacological mechanism regulated by GH acting on depression. Among the cAMP signaling pathway, the major target proteins, namely, cAMP, PKA, CREB, p-CREB, BDNF, were used to verify in the CUMS model rats. The results showed that GH could activate the cAMP-PKA-CREB-BDNF signaling pathway to exert antidepressant effects. Conclusions: An integrative pharmacology-based pattern was used to uncover that GH could increase the contents of DA, NE and 5-HT, activate cAMP-PKA-CREB-BDNF signaling pathway exert antidepressant effects.