Mechanical force increases tooth movement and promotes remodeling of alveolar bone defects augmented with bovine bone mineral.

BACKGROUND: Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. MATERIAL AND METHODS: Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (µCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1ß, IL-4). RESULTS: Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1ß levels, and less active MMP-9 in cell culture. CONCLUSION: This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.

A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization.

To assess resolving-like activity by a novel chemically-modified curcumin (CMC2.24) in a "two-hit" model of diabetes-associated periodontitis. Macrophages from rats were cultured in the presence/absence of either Lipopolysaccharide (LPS, 1st hit); or advanced-glycation-end products (AGE, 2nd hit); or both combined. CMC2.24 was added as treatment. The conditioned media were analyzed for MMP-9, cytokines (IL-1ß, IL-6, TNF-α), resolvins (RvD1, RvE1, lipoxin A4), and soluble receptor for AGE (sRAGE). The phenotypes of M1/M2 macrophage were analyzed by flow cytometry. Both LPS/AGE-alone, and two-combined, dramatically increased the secretion of MMP-9 by macrophages. CMC2.24 "normalized" the elevated levels of MMP-9 under all conditions. Moreover, CMC2.24 significantly reduced the secretion of IL-1ß and IL-6 with a fewer effects on TNF-α. Importantly, CMC2.24 increased RvD1 and sRAGE secretion by macrophages exposed to LPS/AGE; and both treatment groups exhibited increased M2 relative to M1 populations. Furthermore, scatter-diagram showed the macrophages gradually shifted from M1 towards M2 with CMC2.24-treated, whereas LPS/AGE-alone groups remained unchanged. CMC2.24 "normalized" cytokines and MMP-9, but also enhanced RvD1 and sRAGE in macrophages. Crucially, CMC2.24 appears to be a potent inhibitor of the pro-inflammatory M1 phenotype; and a promotor of the pro-resolving M2 phenotype, thus acting like a crucial "switch" to reduce inflammation.

CAR-T Cells in the Treatment of Ovarian Cancer: A Promising Cell Therapy.

Ovarian cancer (OC) is among the most common gynecologic malignancies with a poor prognosis and a high mortality rate. Most patients are diagnosed at an advanced stage (stage III or IV), with 5-year survival rates ranging from 25% to 47% worldwide. Surgical resection and first-line chemotherapy are the main treatment modalities for OC. However, patients usually relapse within a few years of initial treatment due to resistance to chemotherapy. Cell-based therapies, particularly adoptive T-cell therapy and chimeric antigen receptor T (CAR-T) cell therapy, represent an alternative immunotherapy approach with great potential for hematologic malignancies. However, the use of CAR-T-cell therapy for the treatment of OC is still associated with several difficulties. In this review, we comprehensively discuss recent innovations in CAR-T-cell engineering to improve clinical efficacy, as well as strategies to overcome the limitations of CAR-T-cell therapy in OC.

MutL homolog 1 germline mutation c.(453+1_454-1)_(545+1_546-1)del identified in lynch syndrome: A case report and review of literature.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics. CASE SUMMARY: A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it. CONCLUSION: No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

Potential clinical implications of iron metabolism in ovarian endometriosis.

OBJECTIVE: The purpose of this study was to investigate iron metabolism indices in ovarian endometriosis (OEMs) and to demonstrate the potential clinical implications in the initiation and development of OEMs. METHODS: Three datasets in Gene Expression Omnibus (GEO) database were selected to assess the expression levels of iron metabolites in endometrial tissues from patients with EMs and the health. To evaluate the differential expression of serum iron indices , hospitalized patients with OEMs and health examinees in Jilin University Second Hospital from November 2018 to December 2019 were recruited. Serum samples were obtained from 38 patients with OEMs and 36 health examinees. To compare the iron metabolism between peripheral circulation blood and local ectopic lesion, cyst fluid samples were obtained from 15 patients with ovarian chocolate cyst at the time of surgery. Iron metabolism indices include iron, transferrin (TF), ferritin, and unsaturated iron-binding capacity (UIBC)), which were measured by automatic biochemical analyzer. RESULTS: The present study indicated the increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with EMs. The expression of iron and ferritin in cyst fluid of patients with OEMs showed higher than that in serum, the results of TF and UIBC were opposite (P < 0.05). There was no statistical difference in the content of iron metabolites between patients with OEMs and the healthy examinees(P > 0.05). CONCLUSION: The ovarian chocolate cyst fluid and endometriotic tissues in patients with OEMs could more directly reflect the pathological changes of local ectopic lesion, which usually manifested as high levels of free iron and/or iron deposits in the ectopic sites. The implications of our work suggest iron metabolites in the serum may have potentially limited value as circulating biomarkers for OEMs. The iron variation in local lesions may be not only regulated by liver that mainly manipulate the systematic iron homeostasis, but also be tuned by the iron regulatory protein (IRP)/ iron responsive element (IRE) system. In summary, the iron metabolites, especially the iron and ferritin in the cyst fluid and endometriotic tissues, are meaningful biomarkers involved in the process of pathophysiology and pathogenesis of OEMs.

A Novel Modified-Curcumin Promotes Resolvin-Like Activity and Reduces Bone Loss in Diabetes-Induced Experimental Periodontitis.

PURPOSE: Clinically, it is challenging to manage diabetic patients with periodontitis. Biochemically, both involve a wide range of inflammatory/collagenolytic conditions which exacerbate each other in a "bi-directional manner." However, standard treatments for this type of periodontitis rely on reducing the bacterial burden and less on controlling hyper-inflammation/excessive-collagenolysis. Thus, there is a crucial need for new therapeutic strategies to modulate this excessive host response and to promote enhanced resolution of inflammation. The aim of the current study is to evaluate the impact of a novel chemically-modified curcumin 2.24 (CMC2.24) on host inflammatory response in diabetic rats. METHODS: Type I diabetes was induced by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC2.24, or the vehicle-alone, was administered by oral gavage daily for 3 weeks to the diabetics. Micro-CT was used to analyze morphometric changes and quantify bone loss. MMPs were analyzed by gelatin zymography. Cell function was examined by cell migration assay, and cytokines and resolvins were measured by ELISA. RESULTS: In this severe inflammatory disease model, administration of the pleiotropic CMC2.24 was found to normalize the excessive accumulation and impaired chemotactic activity of macrophages in peritoneal exudates, significantly decrease MMP-9 and pro-inflammatory cytokines to near normal levels, and markedly increase resolvin D1 (RvD1) levels in the thioglycolate-elicited peritoneal exudates (tPE). Similar effects on MMPs and RvD1 were observed in the non-elicited resident peritoneal washes (rPW). Regarding clinical relevance, CMC2.24 significantly inhibited the loss of alveolar bone height, volume and mineral density (ie, diabetes-induced periodontitis and osteoporosis). CONCLUSION: In conclusion, treating hyperglycemic diabetic rats with CMC2.24 (a tri-ketonic phenylaminocarbonyl curcumin) promotes the resolution of local and systemic inflammation, reduces bone loss, in addition to suppressing collagenolytic MMPs and pro-inflammatory cytokines, suggesting a novel therapeutic strategy for treating periodontitis complicated by other chronic diseases.

Comparison of achieved and predicted crown movement in adults after 4 first premolar extraction treatment with Invisalign.

INTRODUCTION: In this study, we compared achieved and predicted crown movements of maxillary and mandibular first molars, canines, and central incisors in adults after 4 first premolar extraction treatment with Invisalign. METHODS: Seventeen adult patients who received 4 first premolar extraction treatment with Invisalign and completed the first series of aligners were included. Superimposition of pretreatment and actual posttreatment dental models was acquired using registrations of pretreatment and posttreatment craniofacial models on the basis of bone surfaces and registrations of craniofacial and dental models on the basis of dental crown surfaces, respectively. Superimposition of pretreatment and predicted posttreatment models was acquired from ClinCheck software. Achieved and predicted 3-dimensional crown movements of maxillary and mandibular first molars, canines, and central incisors were then compared using the paired t test. RESULTS: Relative to predicted changes, first molars achieved greater mesial displacement, mesial tipping, and buccal inclination in both the maxilla and mandible, greater intrusion in the maxilla, and greater mesial-lingual rotation and less constriction in the mandible. Canines achieved greater distal tipping in both the maxilla and mandible, less retraction in the maxilla, and greater lingual inclination and extrusion in the mandible. Central incisors achieved greater distal tipping and lingual inclination and extrusion in both the maxilla and mandible and less retraction in the maxilla. CONCLUSIONS: Tooth crown movements were not fully achieved as predicted following Invisalign treatment. Differences focused on mesial tipping, buccal inclination, mesial displacement, and intrusion of the first molars, as well as distal tipping, lingual inclination, insufficient retraction, and intrusion of the canines and central incisors.

Measurement of three-dimensional changes in lip vermilion in adult female patients after orthodontic extraction: a retrospective longitudinal study.

BACKGROUND: 3D facial scanning has changed the way facial aesthetic is evaluated and has numerous advantages for facial analysis. The specific relationship between lip vermilion morphological changes after orthodontic extraction treatment has not been fully explained. The objective of this study was to evaluate 3D morphological changes after orthodontic extraction treatment in lip vermilion of adult females with dentoalveolar protrusion using a structured light-based scanner. METHODS: Forty-two female subjects (25.2 ± 1.9 years) were recruited as the treatment group; these patients had undergone extraction treatment and achieved better sagittal profiles. Twenty female subjects (25.5 ± 2.1 years) were enrolled in the non-treatment group; these patients did not require any orthodontic treatment. The follow up time for the treatment group was more than 24 months and for the non-treatment group was more than 12 months. 3D facial scans were captured using 3D CaMega. Six landmarks (Ls, Li, R.Chp, L.Chp, R.Ch, and L.Ch), three linear measurements (mouth height, philtrum width, and mouth width), and three area measurements (upper, lower, and total vermilion area) were measured. The spatial deviations of three volumetric measurements (upper, lower, and total vermilion) were constructed for quantitative analysis. Color-coded displacement map were constructed for visualization of the soft-tissue displacement as qualitative evaluation. RESULTS: Mouth height and philtrum width decreased (-0.93 mm and - 1.08 mm, respectively) significantly (p = 0.008 and p = 0.027, respectively), and no significant (p = 0.488) change in mouth width was observed in the treatment group. The lower and total vermilion surface areas decreased (-51.00mm2 and - 69.82mm2, respectively) significantly (p = 0.003 and p = 0.031, respectively) in the treatment group, but no statistically significant (p = 0.752) change was detected in the upper vermilion. In the treatment group, significant retractions were observed in the color-coded displacement map, and three volumetric measurements of vermilion changed significantly (p = 0.012, p = 0.001 and p = 0.004, respectively). Significant differences were found between the treatment group and the non-treatment group in the linear, area and volumetric measurements. CONCLUSIONS: This study established a method for qualitative and quantitative evaluation of the lip vermilion. Significant 3D retraction of the lip vermilion after the extraction treatment was found, with morphological variation between upper and lower vermilion.

Analysis of correlation of 3-dimensional lip vermilion morphology and dentoskeletal forms in young Chinese adults on the basis of sex and skeletal patterns.

INTRODUCTION: The objective of this research was to evaluate the correlation between 3-dimensional (3D) lip vermilion (LV) morphology and skeletal patterns as well as incisor measurements in young Chinese adults. METHODS: In all, 240 young adults were enrolled; these included 80 patients each with skeletal Class I, Class II, and Class III malocclusions, respectively. Each sagittal skeletal pattern included 40 male and 40 female subjects. Twenty-two 3D LV measurements were obtained from 3D facial scans. Skeletal and incisor measurements were evaluated on lateral cephalograms. Correlation and regression analysis were performed between soft and hard tissue measurements. RESULTS: Six of 22 LV measurements showed significant differences between male and female subjects. The 3D LV morphology showed significant differences with respect to different skeletal patterns and sex. Adults with skeletal Class III malocclusion tended to have thinner upper vermilion and fuller lower vermilion than subjects with skeletal Class II and III malocclusion. The mandibular plane angle negatively correlated with the upper-lower vermilion midsagittal curve length and surface area ratio in adults with skeletal Class I and II malocclusion, yet the vertical facial skeletal type showed no correlation in adults with skeletal Class III malocclusion. The vermilion angle, central bow angle, vermilion height, vermilion midsagittal curve length, vermilion height and width ratio, and vermilion surface area showed a significant correlation with incisor measurements. Regression analysis found that the ANB angle was an important factor affecting the upper and lower vermilion midsagittal curve length and surface area ratio. Further, the vermilion height and height and width ratio were closely correlated with the interincisal (U1/L1) angle, whereas the central bow angle was closely correlated with the maxillary incisor torque. CONCLUSIONS: Most LV morphology variables were correlated to skeletal patterns and incisor measurements. Skeletal Class III malocclusion showed significant differences in vermilion morphology. Both the sagittal and vertical skeletal pattern have effects on vermilion proportion. The incisor torque was closely correlated to vermilion shape and central bow angle and might influence the vermilion esthetics. However, the proportion of the upper and lower vermilion was mainly affected by the ANB angle.

HIF-1α Is a Rational Target for Future Ovarian Cancer Therapies.

Ovarian cancer is the eighth most commonly diagnosed cancer among women worldwide. Even with the development of novel drugs, nearly one-half of the patients with ovarian cancer die within five years of diagnosis. These situations indicate the need for novel therapeutic agents for ovarian cancer. Increasing evidence has shown that hypoxia-inducible factor-1α(HIF-1α) plays an important role in promoting malignant cell chemoresistance, tumour metastasis, angiogenesis, immunosuppression and intercellular interactions. The unique microenvironment, crosstalk and/or interaction between cells and other characteristics of ovarian cancer can influence therapeutic efficiency or promote the disease progression. Inhibition of the expression or activity of HIF-1α can directly or indirectly enhance the therapeutic responsiveness of tumour cells. Therefore, it is reasonable to consider HIF-1α as a potential therapeutic target for ovarian cancer. In this paper, we summarize the latest research on the role of HIF-1α and molecules which can inhibit HIF-1α expression directly or indirectly in ovarian cancer, and drug clinical trials about the HIF-1α inhibitors in ovarian cancer or other solid malignant tumours.

The role of BMP15 and GDF9 in the pathogenesis of primary ovarian insufficiency.

Endocrine and paracrine signals can be key regulators of ovarian physiology. The oocyte secretes growth factors which directly induce follicular development by a complex paracrine signalling process, and the transforming growth factorß (TGF-ß) superfamily has a pivotal role in this process. The bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes are relevant members of the TGF-ß superfamily that encode proteins secreted by the oocytes into the ovarian follicles, where they contribute to creating an environment supporting follicle selection and growth. Their main functions include regulating cellular proliferation/differentiation, follicular survival/atresia, and oocyte maturation. Recent functional studies have validated genetic factors (Progesterone receptor membrane component 1 (PGRMC1)), Fragile X mental retardation 1 (FMR1, GDF9 and BMP15) as being causative of primary ovarian insufficiency (POI), BMP15/GDF9 gene variants were found to have a high incidence on the POI phenotype. This review considers the most recent research regarding the role of BMP15 and GDF9 in the genetic control of follicular development, paying special attention to the pathogenesis of POI.

HDAC11: a rising star in epigenetics.

Epigenetic mechanisms, such as acetylation, methylation, and succinylation, play pivotal roles in the regulation of multiple normal biological processes, including neuron regulation, hematopoiesis, bone cell maturation, and metabolism. In addition, epigenetic mechanisms are closely associated with the pathological processes of various diseases, such as metabolic diseases, autoimmune diseases and cancers. Epigenetic changes may precede genetic mutation, so research on epigenetic changes and regulation may be important for the early detection and diagnosis of disease. Histone deacetylase11 (HDAC11) is the newest member of the histone deacetylase (HDAC) family and the only class IV histone deacetylase. HDAC11 has different expression levels and biological functions in different systems of the human body and is among the top 1 to 4% of genes overexpressed in cancers, such as breast cancer, hepatocellular carcinoma and renal pelvis urothelial carcinoma. This article analyzes the role and mechanism of HDAC11 in disease, especially in tumorigenesis, in an attempt to provide new ideas for clinical and basic research.

Non-optimal effectiveness of convalescent plasma transfusion and hydroxychloroquine in treating COVID-19: a case report.

BACKGROUND: Convalescent plasma (CP) transfusion was reported to be effective in treating critically ill patients with COVID-19, and hydroxychloroquine could potently inhibit SARS-CoV-2 in vitro. Herein, we reported a case receiving combination therapy with CP transfusion and hydroxychloroquine for the first time. CASE PRESENTATION: Laboratory findings showed high lactic acid level (2.1 mmol/L) and C-reactive protein (CRP, 48.8 mg/L), and low white blood cell count (1.96 × 109/L) in a 65-year-old Chinese man, who was diagnosed with severe COVID-19. CP was intravenously given twice, and hydroxychloroquine was orally administrated for a week (0.2 g, three times a day). The lactic acid and C-reactive protein levels remained high (2.1 mmol/L and 73.23 mg/L, respectively), while the arterial oxyhemoglobin saturation decreased to 86% with a low oxygenation index (OI, 76 mmHg) on day 4 after CP transfusion. His temperature returned to normal and the OI ascended above 300 on day 11. Moreover, the RNA test remained positive in throat swab, and computed tomography revealed severe pulmonary lesions on day 11 after admission. CONCLUSION: These findings suggested that the effectiveness of combination therapy with CP and hydroxychloroquine may be non-optimal, and specific therapy needs to be explored.

Three-dimensional analysis of the physiologic drift of adjacent teeth following maxillary first premolar extractions.

We assessed the three-dimensional (3D) pattern of the physiologic drift of the remaining adjacent teeth after premolar extraction due to orthodontic reasons and the associated factors. Data were collected from 45 patients aged 17.04 ± 5.14 years who were scheduled to receive a fixed appliance after maxillary premolar extraction. Seventy-five drift models were obtained and digitalized via 3D scanning. The average physiologic drift duration was 81.66 ± 70.03 days. Angular and linear changes in the first molars, second premolars, and canines were measured using the 3D method. All the examined teeth had tipped and moved towards the extraction space, leading to space decreases. Posterior teeth primarily exhibited significant mesial tipping and displacement, without rotation or vertical changes. All canine variables changed, including distal inward rotation and extrusion. The physiologic drift tended to slow over time. Age had a limited negative effect on the mesial drift of posterior teeth, whereas crowding had a limited positive effect on canine drift. Thus, the mesial drift of molars after premolar extraction may lead to molar anchorage loss, particularly among younger patients. The pattern of the physiologic drift of maxillary canines can help relieve crowding and facilitate labially ectopic canine alignment, whereas canine drift is accelerated by more severe crowding.

TRP14 promotes resistance to cisplatin by inducing autophagy in ovarian cancer.

Cisplatin is a common chemotherapeutic agent against ovarian cancer; however, drug resistance is a major limiting factor for its use in clinical treatment. The underlying mechanisms of cisplatin resistance in ovarian cancer have not yet been fully elucidated. Thus, this study aimed to elucidate some of the mechanisms responsible for resistance to cisplatin in ovarian cancer. The results demonstrated that the cisplatin­resistant human ovarian cancer cell lines, SKOV3/DDP and A2780/DDP, exhibited higher autophagy levels than the control ovarian cancer cell lines, SKOV3 and A2780. Moreover, autophagy inhibition by 3­methyladenine or shRNA against autophagy­related gene (ATG)5 potentiated the cytotoxicity induced by cisplatin, whereas autophagy induction by rapamycin (Rapa) increased cell survival. Exposure to cisplatin induced an upregulation in the expression of thioredoxin­related protein of 14 kDa (TRP14). Furthermore, TRP14 knockdown or overexpression decreased or increased the autophagy response and cisplatin resistance, and this effect was reversed by treatment with Rapa or ATG5 knockdown. The findings of this study also suggested that TRP14 induced autophagy and chemoresistance via the 5'AMP­activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. Importantly, the data from a tissue array revealed a positive association between TRP14 and Beclin1 in human ovarian cancer and marginal tissues. These findings have identified, for the first time, to the best of our knowledge, that TRP14 induces autophagy and consequently cisplatin resistance in ovarian cancer cells via the AMPK/mTOR/p70S6K signaling pathway. This in turn renders TRP14 as a potential predictor or target in ovarian cancer therapy.

Three-dimensional changes in lip vermilion morphology of adult female patients after extraction and non-extraction orthodontic treatment.

OBJECTIVE: To investigate the three-dimensional lip vermilion changes after extraction and non-extraction orthodontic treatment in female adult patients and explore the correlation between lip vermilion changes and incisor changes. METHODS: Forty-seven young female adult patients were enrolled in this study (skeletal Class III patients were excluded), including 34 lip-protruding patients treated by extraction of four first premolars (18 patients requiring mini-implants for maximum anchorage control and 16 patients without mini-implants) and 13 patients requiring non-extraction treatment. Nine angles, seven distances, and the surface area of the lip vermilion were measured by using pre- and post-treatment three-dimensional facial scans. Linear and angular measurements of incisors were performed on lateral cephalograms. RESULTS: There were no significant changes in the vermilion measurements in the non-extraction group. The vermilion angle, vermilion height, central bow angle, height/width ratio, and vermilion surface area decreased significantly after the orthodontic treatment in the extraction groups, but the upper/lower vermilion proportion remained unchanged. Significant correlations were found between the changes in incisor position and those in vermilion angles, vermilion height, and surface area. CONCLUSIONS: Extraction of the four first premolars probably produced an aesthetic improvement in lip vermilion morphology. However, the upper/lower vermilion proportion remained unchanged. The variations in the vermilion were closely related to incisor changes, especially the upper incisor inclination changes.

Comparison of achieved and predicted tooth movement of maxillary first molars and central incisors: First premolar extraction treatment with Invisalign.

OBJECTIVES: To compare achieved and predicted tooth movements of maxillary first molars and central incisors in first premolar extraction cases treated with Invisalign. MATERIALS AND METHODS: The present study included 30 patients who received maxillary first premolar extraction treatment with Invisalign. The actual posttreatment model was registered with the pretreatment model on the palatal stable region and superimposed with the virtual posttreatment model. Achieved and predicted tooth movements of maxillary first molars and central incisors were compared using paired t-test. Linear mixed-effect model analyses were used to explore the influence of age (adolescents vs adults), attachment (G6-optimized vs 3-mm vertical, 3-mm horizontal, and 5-mm horizontal), and initial crowding on the differences between predicted and achieved tooth movement (DPATM). RESULTS: First molars achieved greater mesial tipping, mesial translation, and intrusion than predicted. Central incisors achieved less retraction and greater lingual crown torque and extrusion than predicted. Adolescents showed greater DPATM in the mesiodistal translation of first molars and labiolingual translation of central incisors and smaller DPATM in the occlusogingival translation of the first molars and crown torque of the central incisors than adults. The 3-mm vertical attachment group showed greater DPATM in the mesiodistal translation of the first molars vs the G6-optimized attachment group. Initial crowding had an inverse correlation with DPATM in angulation and mesiodistal translation of the first molars. CONCLUSIONS: First molar anchorage control and central incisor retraction were not fully achieved as predicted in first premolar extraction treatment with Invisalign. Age, attachment, and initial crowding affected the differences between predicted and achieved tooth movement.

Impaired Th17 cell proliferation and decreased pro-inflammatory cytokine production in CXCR3/CXCR4 double-deficient mice of vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is a common observed infection, affecting approximately 75% of women of reproductive age. Drug resistance represents a troublesome stumbling block associated with VVC therapy. Thus the aim of the present study was to provide information regarding the selection of potential drug targets for VVC. CXCR3-, CXCR4-, or CXCR/CXCR4 double-deficient mouse models of VVC were subsequently established, with changes to the load of Candida Albicans evaluated accordingly. The biological behaviors of the vaginal epithelial cells were characterized in response to the CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout in vivo. Our initial observations revealed that in mice with VVC, CXCR3-, CXCR4-, or CXCR3 - CXCR4 double-knockout resulted in a decreased load of C. Albicans as well as reduced levels and proportion of Th17 cells. Proinflammatory cytokine production was found to be inhibited by CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout whereby the mRNA and protein expressions CXCR3, CXCR4, IL-17, IL-6, and TNF-α exhibited decreased levels. CXCR3-, CXCR4-, or CXCR3/CXCR4 double-knockout appeared to function as positive proliferation factors, while playing a negative role in the processes of apoptosis and the cell cycle of vaginal epithelial cells. Taken together, the key findings of the study suggested that CXCR3/CXCR4 double-knockout could act to hinder the progression of VVC, highlighting its promise as a novel therapeutic target in the treatment of VVC. CXCR3 and CXCR4 genes may regulate Th17/IL-17 immune inflammatory pathways to participate in antifungal immunity.

First human infection by a novel avian influenza A(H7N4) virus.

Multiple reassortant strains of novel, highly pathogenic avian influenza A have recently emerged and spread over the world. Here we report on a 68-year-old woman in Jiangsu, China, with influenza A(H7N4) infection and associated illness, which strongly demonstrating the ability of the virus to spread from animals to humans and thus emphasizing the importance of continuous surveillance of the emerging viruses.

Comparison of orthodontic tooth movement between adolescents and adults based on implant superimposition.

OBJECTIVE: We compared tooth movement under maximum anchorage control with mini-screw implants in growing and non-growing patients. METHODS: In total, 15 adolescent (G1) and 19 adult (G2) patients with prognathic profiles were selected. All patients underwent first premolar extraction treatment with mini-screw implants for maximum anchorage control. Cone-beam computed tomography (CBCT) data were obtained immediately after implant placement (T1) and at the end of anterior tooth retraction (T2). Tooth movement and root length changes of the maxillary first molar, canine, and incisors were evaluated with three-dimensional models constructed using CBCT data obtained before and after orthodontic retraction through the superimposition of stable implants. RESULTS: Distal movement of the molar crown was observed in G2, but mesial movement was observed in G1. Mesial tipping of the first molar (1.82 ± 6.76°) was seen in G1 and distal tipping (4.44 ± 3.77°) was observed in G2. For the canines, mesial crown tipping (0.33 ± 4.99°) was noted in G1 and distal crown tipping (8.00 ± 5.57°) was observed in G2. In adults, the lingual inclinations of the lateral and central incisors were 11.91 ± 7.01° and 11.47 ± 6.70°, with 0.99 ± 1.22 mm and 1.08 ± 1.20 mm root retraction, respectively. In adolescents, the torque changes were smaller (lateral incisors, 8.25 ± 10.15°; central incisors, 9.82 ± 8.97°) and the root retractions were 0.31 ± 1.81 mm and 0.77 ± 1.59 mm, respectively. Less shortening of the central incisor roots occurred in adolescents than in adults. CONCLUSIONS: Tooth movements, such as anchor molar angular change, the canine tipping pattern, and the amount of incisor retraction, differed between adolescents and adults treated using the same anchorage with mini-screw implants, bracket prescription, and en masse retraction method. Anchorage strength of the first molars, canine movement patterns, and incisor retraction ranges are not determined by the anchorage device alone; growth and alveolar limitations also play roles.