Objective:The aim of this study was to assess the esthetic and clinical outcomes of immediate implantation using the conventional flap-less approach and the socketshield technique (SST).Methods: This study included 30 adult patients who underwent anterior teeth replacement and fulfilled the pre-defined criteria. Patients were randomly allocated to the SST (n = 15) and conventional flap-less (control, n = 15) groups. The esthetic outcomes were evaluated by assessing the degree of soft-tissue recession and the pink esthetic scores (PESs). Clinical parameters, including the modified plaque index, modified sulcus bleeding index (mSBI), probing depth (PD), and implant stability quotient (ISQ), were assessed. The buccal plate width (BPW) and height (BPH) were also measured.Results: Implantation was clinically successful for all subjects in both groups. With a similar baseline, the SST group exhibited less reduction in the midfacial mucosal margins and the height of the mesial and distal papillae as well as higher BPW and BPH values compared with the control group (p < .001). The ISQ values were 76.01 ± 1.31 for the SST group and 75.56 ± 1.07 for the control group (p > .05), suggesting sufficient initial stability in both groups. At the 24-month follow-up, SST group patients had statistically significant lower values of PD, mSBI, and mPLI compared with the control group. There were no significant differences in the overall and individual PES values for both groups.Conclusion: SST may improve functional and esthetic outcomes by maintaining alveolar bone volume and peri-implant tissues. SST seems to be a promising treatment approach for implants in the esthetic zone. K E Y W O R D S alveolar bone, esthetic outcome, immediate implant, pink esthetic score, restoration S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Sun C, Zhao J, Liu Z, et al. Comparing conventional flap-less immediate implantation and socketshield technique for esthetic and clinical outcomes: A randomized clinical study. Clin Oral Impl Res. 2020;31:181-191. https ://doi.

BackgroundInterleukin-2 (IL-2) serves as a pioneer of immunotherapeutic agent in cancer treatment. However, there is a considerable proportion of patients who cannot benefit from this therapy due to the limited clinical responses and dose-limiting toxicities. Mounting evidence indicates that commensal microbiota shapes the outcome of cancer immunotherapies. In this study, we aim to investigate the enhancing effect of Akkermansia muciniphila (AKK), a beneficial commensal microbe receiving considerable attentions, on the antitumor efficacy of IL-2 and explore the underlying molecular mechanism.MethodsColorectal carcinoma patient-derived tumor tissues were used to evaluate the therapeutic efficacy of combination treatment. AKK was orally delivered to B16F10 and CT26 tumor-bearing mice along with systemic IL-2 treatment. Flow cytometry was carried out to analyze the tumor immune microenvironment. The molecular mechanism of the enhanced therapeutic efficacy was explored by RNA-seq and then verified in tumor-bearing mice.ResultsCombined treatment with IL-2 and AKK showed a stronger antitumor efficacy in colorectal cancer patient-derived tumor tissues. Meanwhile, the therapeutic outcome of IL-2 was significantly potentiated by oral administration of AKK in subcutaneous melanoma and colorectal tumor-bearing mice, resulting from the strengthened antitumor immune surveillance. Mechanistically, the antitumor immune response elicited by AKK was partially mediated by Amuc, derived from the outer membrane protein of AKK, through activating toll-like receptor 2 (TLR2) signaling pathway. Besides, oral supplementation with AKK protected gut barrier function and maintained mucosal homeostasis under systemic IL-2 treatment.ConclusionThese findings propose that IL-2 combined with AKK is a novel therapeutic strategy with prospecting application for cancer treatment in clinical practice.

Galunisertib (Gal) is a transforming growth factor (TGF-β) blockade which is being investigated as a potential tumor immunotherapy candidate drug in clinical trials. However, primary or acquired resistance is often found in the recruited cancer patients, which limits its clinical application. Tumor immune microenvironment can be regulated by intestinal microbiota, leading to different therapeutic outcomes. It is hypothesized that manipulation of cancer patients' intestinal microbiome in the early stage of therapy may be a promising strategy to improve the therapeutic efficacy of Gal. Methods : 4T1 and H22 subcutaneous tumor bearing mice were used to evaluate the therapeutic effect. Escherichia coli strain Nissle 1917 (EcN), a widely used probiotic bacteria, was orally delivered to the tumor bearing mice daily along with Gal treatment. Antitumor effect of the combination therapy was evaluated by tumor volume, histological staining of tumor tissues. Furthermore, flow cytometry was performed to analyze the alteration of immune microenvironment in tumor bed after treatment. The suppressing effect of the combination therapy on tumor invasiveness and metastasis was evaluated in both mice and zebrafish xenografts models. Fecal sample 16S rRNA gene sequencing was conducted to analyze changes of intestinal microbial diversity. The effect of intestinal microbiota on tumor suppression after receiving EcN was further tested by fecal transplant. Results : The therapeutic outcomes in tumor growth inhibition and metastasis suppression of Gal were significantly potentiated by EcN, resulting from the strengthened antitumor immunity. EcN was able to relieve the immunosuppressive tumor microenvironment, which was evidenced by enhanced tumor-specific effector T cells infiltration and dendritic cells activation. Intestinal microbiota was modulated by EcN, illustrated by a shift of gut microbiome toward certain beneficial bacteria. Conclusion : These results suggested that Gal combined with EcN might be a novel therapeutic approach with great potential of clinical implications for cancer prevention or treatment.

Recent understanding of the mechanism of immunoglobulin G (IgG) catabolism has yielded new insight into antibody-mediated diseases. We proposed that β2-microglobulin (β2m)–deficient mice have been protected from systemic lupus erythematosis (SLE)–like syndromes because they lack the β2m-associated IgG protection receptor (FcRn) and therefore catabolize IgG, including pathogenic IgG autoantibodies, considerably more rapidly than normal mice. Such an hypothesis would predict that β2m-deficient mice would also be resistant to experimental bullous pemphigoid, a disease with a pathogenesis thought to be much simpler than SLE, being the result of antibody directed toward a pathogenic epitope on the epidermal hemidesmosome that anchors basal keratinocytes to the basement membrane. To test this hypothesis, we administered pathogenic rabbit antibody directed toward the hemidesmosome to β2m-deficient mice and to normal control mice, both intraperitoneally and intradermally, and assessed the mice clinically, histologically, and immunologically for manifestations of skin disease. We found that the β2m-deficient mice were protected when the antibody was given intraperitoneally whereas intradermal administration resulted in blisters only slightly less severe than those seen in normal mice. These data would indicate that autoantibody-mediated inflammation might be prevented or controlled by appropriate modulation of FcRn function.

Digestive malignancies are the leading cause of mortality among all neoplasms, contributing to estimated 3 million deaths in 2012 worldwide. The mortality rate hassurpassed lung cancer and prostate cancer in recent years. The transcription factor Forkhead Box O1 (FOXO1) is a key member of Forkhead Box family, regulating diverse cellular functions during tumor initiation, progression and metastasis. In this review, we focus on recent studies investigating the antineoplastic role of FOXO1 in digestive malignancy. This review aims to serve as a guide for further research and implicate FOXO1 as a potent therapeutic target in digestive malignancy.

Aims To investigate the effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) combined with deep breathing training (DBT) on refractory gastroesophageal reflux disease (rGERD). Methods Twenty‐one patients with rGERD were recruited and randomly assigned to receive either only esomeprazole (ESO, 20 mg bid) (group A, n = 7), TEA + DBT + ESO (group B, n = 7), or sham‐TEA + DBT + ESO (group C, n = 7) in a four‐week study. The reflux diagnostic questionnaire (RDQ) score and heart rate variability (HRV) were recorded and evaluated at baseline and at the end of each treatment. Blood samples were collected for the measurement of serum acetylcholine (Ach) and nitric oxide (NO). Esophageal manometry and 24‐hour pH monitoring were performed before and after the treatment. Results After treatment, 1) the participants in group B had significantly lower scores of RDQ and DeMeester and increased lower esophageal sphincter pressure (LESP) than those in group C (all p < 0.05), suggesting the role of TEA; 2) low frequency band (LF)/(LF + HF) ratio in groups B and C was decreased, compared with group A (p = 0.010, p = 0.042, respectively); high frequency band (HF)/(LF + HF) ratio in B and C groups was significantly increased, compared with group A (p = 0.010, p = 0.042, respectively); 3) The serum Ach in groups B and C was significantly higher than group A (p = 0.022, p = 0.046, respectively); the serum NO in groups B and C was significantly lower than group A (p = 0.010, p = 0.027, respectively). Conclusions TEA combined with the DBT can effectively improve the reflux symptoms in rGERD patients by increasing LESP and reducing gastroesophageal reflux, which may be mediated via the autonomic and enteric mechanisms.

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Recent clinical studies have demonstrated a beneficial effect of Saccharomyces boulardii (S. boulardii) in inflammatory bowel disease (IBD). However, the detailed mechanisms underlying remain poorly defined. In this study, we...