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Abstract Background This dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB). Methods A total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance. Results In both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB. Conclusion Isoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM.

ObjectiveTo investigate the risk factors associated with Multidrug-resistant tuberculosis (MDR-TB) in people with drug-resistant tuberculosis (DR-TB) and develop a predictive model.MethodsA total of 893 individuals with DR-TB treated at Wenzhou Central Hospital from January 2018 to December 2022 were included in the study after excluding 178 individuals with incomplete clinical and laboratory data, leaving 715 individuals for analysis. Data on demographic information, baseline clinical characteristics, laboratory and imaging results, and clinical diagnosis were collected to identify the risk factors for MDR-TB and establish a predictive model.ResultsMultivariate logistic regression analysis identified residence in rural areas, retreatment of TB, presence of pulmonary cavity, uric acid (UA) ≥ 346 μmol/L and c-reactive protein (CRP)

Abstract Ischaemic bowel disease (ICBD) is a group of intestinal ischaemia syndromes caused by various aetiologies of reduced intestinal blood flow or vascular occlusion. ICBD can present as abdominal pain, bloody stool, and diarrhoea. This disease often occurs in middle-aged and elderly individuals with cardiovascular and cerebrovascular diseases. The incidence of ischaemic bowel disease has been increasing for decades, and it is difficult to diagnose, resulting in rapid disease progression and a high mortality rate. Therefore, fully understanding this disease, improving the diagnosis rate of this disease, and finding appropriate treatment methods are urgently needed to improve the condition and prognosis of patients. Umbilical cord blood stem cells are accessible, have weak immunogenicity, and have various biological functions, such as angiogenesis, inflammation and immune regulation. Many studies have confirmed that cord blood stem cells can relieve ischaemia, and these cells have attracted tremendous amounts of attention in regenerative medicine in recent years. In this paper, we discuss the clinical characteristics of ICBD, analyse the characteristics of human umbilical cord blood mononuclear cells (HUCB-MNCs), and use its to treat ischaemic bowel disease. Additionally, we compare the clinical manifestations and related indicators before and after treatment to evaluate the efficacy and safety of these methods.

Abstract Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Nanomaterials constructed based on specific goals can be employed to activate endogenous growth factor‐related signaling. In this study, based on the conventional single‐stranded DNA self‐assembly into tetrahedral framework nucleic acids (tFNAs), the Apt02 nucleic acid aptamer and dimethyloxallyl glycine (DMOG) small molecule are integrated into a complex via a template‐based click chemistry reaction and toehold‐mediated strand displacement reaction. Thus, being able to simulate the VEGF (vascular endothelial growth factor) function and stabilize HIF (hypoxia‐inducible factor), a functional whole is constructed and applied to angiogenesis. Cellular studies demonstrate that the tFNAs‐Apt02 complex (TAC) has a conspicuous affinity to human umbilical vein endothelial cells (HUVECs). Further incubation with DMOG yields the tFNAs‐Apt02‐DMOG complex (TACD), which promotes VEGF secretion, in vitro blood vessel formation, sprouting, and migration of HUVECs. Additionally, TACD enhances angiogenesis by upregulating the VEGF/VEGFR and HIF signaling pathways. Moreover, in a diabetic mouse skin defect repair process, TACD increases blood vessel formation and collagen deposition, therefore accelerating wound healing. The novel strategy simulating VEGF and stabilizing HIF promotes blood‐vessel formation in vivo and in vitro and has the potential for broad applications in the vascularization field.

In the mining vibrating screen’s working process, the support spring often fails due to alternating loads and a poor working environment. The six-degrees-of-freedom simplified rigid body dynamic model is established to obtain the vibration response of the mining vibrating screen with a faulty single-group spring and is verified using the ABAQUS (2020) simulation in this paper. Unlike previous studies focusing on multiple-group spring failures or using lower-degree-of-freedom models, this study addresses the common single-group spring failure with the comprehensive model capturing complex spatial motion. This study also reveals that the vibration angle can be used to diagnose the failure location, while the vibration displacement can be used to evaluate the health state of single-group springs. Based on these rules, the novel method for locating a faulty spring group and new evaluation formulas for their health states are validated by the simulations. The results indicate that the failure location is accurately diagnosed, and the errors of the health state evaluation are minimal. The evaluated values are 66.12% and 85.56% when the health states of the spring groups at the feed side and the out-feed side are 65% and 85%, respectively. Therefore, this diagnostic model provides significant theoretical assistance for diagnosing single-group spring failure in the mining vibrating screen, enhancing maintenance strategies and operational reliability.

Abstract This study aimed to introduce a minimally invasive technique for maxillary sinus floor elevation using the lateral approach (lSFE) and to determine the factors that influence the stability of the grafted area in the sinus cavity. Thirty patients (30 implants) treated with lSFE using minimally invasive techniques from 2015 to 2019 were included in the study. Five aspects of the implant (central, mesial, distal, buccal, and palatal bone heights [BHs]) were measured using cone-beam computed tomography (CBCT) before implant surgery, immediately after surgery (T0), 6 months after surgery (T1), and at the last follow-up visit (T2). Patients’ characteristics were collected. A small bone window (height, (4.40 ± 0.74) mm; length, (6.26 ± 1.03) mm) was prepared. No implant failed during the follow-up period (3.67 ± 1.75) years. Three of the 30 implants exhibited perforations. Changes in BH of the five aspects of implants showed strong correlations with each other and BH decreased dramatically before second-stage surgery. Residual bone height (RBH) did not significantly influence BH changes, whereas smoking status and type of bone graft materials were the potentially influential factors. During the approximate three-year observation period, lSFE with a minimally invasive technique demonstrated high implant survival rate and limited bone reduction in grafted area. In conclusion, lSFE using minimally invasive techniques was a viable treatment option. Patients who were nonsmokers and whose sinus cavity was filled with deproteinized bovine bone mineral (DBBM) had significantly limited bone resorption in grafted area.

Abstract Background Diabetes-related osteoporosis (DOP) is a chronic disease caused by the high glucose environment that induces a metabolic disorder of osteocytes and osteoblast-associated mesenchymal stem cells. The processes of bone defect repair and regeneration become extremely difficult with DOP. Adipose-derived stem cells (ASCs), as seed cells in bone tissue engineering technology, provide a promising therapeutic approach for bone regeneration in DOP patients. The osteogenic ability of ASCs is lower in a DOP model than that of control ASCs. DNA methylation, as a mechanism of epigenetic regulation, may be involved in DNA methylation of various genes, thereby participating in biological behaviors of various cells. Emerging evidence suggests that increased DNA methylation levels are associated with activation of Wnt/β-catenin signaling pathway. The purpose of this study was to investigate the influence of the diabetic environment on the osteogenic potential of ASCs, to explore the role of DNA methylation on osteogenic differentiation of DOP-ASCs via Wnt/β-catenin signaling pathway, and to improve the osteogenic differentiation ability of ASCs with DOP. Methods DOP-ASCs and control ASCs were isolated from DOP C57BL/6 and control mice, respectively. The multipotency of DOP-ASCs was confirmed by Alizarin Red-S, Oil Red-O, and Alcian blue staining. Real-time polymerase chain reaction (RT-PCR), immunofluorescence, and western blotting were used to analyze changes in markers of osteogenic differentiation, DNA methylation, and Wnt/β-catenin signaling. Alizarin Red-S staining was also used to confirm changes in the osteogenic ability. DNMT small interfering RNA (siRNA), shRNA-Dnmt3a, and LVRNA-Dnmt3a were used to assess the role of Dnmt3a in osteogenic differentiation of control ASCs and DOP-ASCs. Micro-computed tomography, hematoxylin and eosin staining, and Masson staining were used to analyze changes in the osteogenic capability while downregulating Dnmt3a with lentivirus in DOP mice in vivo. Results The proliferative ability of DOP-ASCs was lower than that of control ASCs. DOP-ASCs showed a decrease in osteogenic differentiation capacity, lower Wnt/β-catenin signaling pathway activity, and a higher level of Dnmt3a than control ASCs. When Dnmt3a was downregulated by siRNA and shRNA, osteogenic-related factors Runt-related transcription factor 2 and osteopontin, and activity of Wnt/β-catenin signaling pathway were increased, which rescued the poor osteogenic potential of DOP-ASCs. When Dnmt3a was upregulated by LVRNA-Dnmt3a, the osteogenic ability was inhibited. The same results were obtained in vivo. Conclusions Dnmt3a silencing rescues the negative effects of DOP on ASCs and provides a possible approach for bone tissue regeneration in patients with diabetic osteoporosis.

Abstract Guided bone regeneration (GBR) uses resorbable and non-resorbable membranes as biological barriers. This study compared the differences in hard tissue stability between GBR using evidence-based digital titanium mesh and resorbable collagen membranes during implant placement. A total of 40 patients (65 implant sites) were enrolled and divided into two groups: resorbable membrane and digital titanium mesh groups. The alveolar bone was analyzed at two- and three-dimensional levels using cone-beam computed tomography and by reconstructing and superimposing the hard tissues at four time points: preoperatively, postoperatively, before second-stage surgery, and 1 year after loading. The use of digital titanium mesh showed less alveolar bone resorption in vertical and horizontal directions two-dimensionally before the second-stage surgery and 1 year after loading. Regarding volumetric stability, the percentage of resorption after 6 months of healing with resorbable membrane coverage reached 37.5%. However, it was only 23.4% with titanium mesh. Although postoperative bone volume was greater at all labial sites with resorbable membrane than with digital titanium mesh, after substantial bone resorption within 1 year of loading, the labial bone thickness at the upper part of implants was thinner with resorbable membrane than with digital titanium mesh. Furthermore, digital titanium meshes made according to ideal bone arch contour reduced soft tissue irritation, and the exposure rate was only 10%. Therefore, although both resorbable membrane and digital titanium mesh in GBR were able to successfully reconstruct the bone defect, digital titanium meshes were better at maintaining the hard tissue volume in the osteogenic space.

Periodontitis is a common disease that causes periodontium defects and tooth loss. Controlling inflammation and tissue regeneration are two key strategies in the treatment of periodontitis. Tetrahedral framework nucleic acids can modulate multiple biological behaviors, and thus, their biological applications have been widely explored. In this study, we investigated the effect of tFNAs on periodontium under inflammatory conditions. Lipopolysaccharide and silk ligature were used to induce inflammation in vivo and in vitro. The results displayed that tFNAs decreased the release of pro-inflammatory cytokines and levels of cellular reactive oxygen species in periodontal ligament stem cells, which promoted osteogenic differentiation. Furthermore, animal experiments showed that tFNAs ameliorated the inflammation of the periodontium and protect periodontal tissue, especially reducing alveolar bone absorption by decreasing inflammatory infiltration and inhibiting osteoclast formation. These findings suggest that tFNAs can significantly improve the therapeutic effect of periodontitis and have the great potential significance in the field of periodontal tissue regeneration.

Abstract Background Diabetic osteoporosis (DOP) is a systemic metabolic bone disease caused by diabetes mellitus (DM). Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Our previous study confirmed that ASCs from DOP mice (DOP-ASCs) have a lower osteogenesis potential compared with control ASCs (CON-ASCs). However, the cause of this poor osteogenesis has not been elucidated. Therefore, this study investigated the underlying mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics and explored methods to enhance their osteogenic capacity. Methods The expression level of JNK1-associated membrane protein (JKAMP) and degree of DNA methylation in CON-ASCs and DOP-ASCs were measured by mRNA expression profiling and MeDIP sequencing, respectively. JKAMP small interfering RNA (siRNA) and a Jkamp overexpression plasmid were used to assess the role of JKAMP in osteogenic differentiation of CON-ASCs and DOP-ASCs. Immunofluorescence, qPCR, and western blotting were used to measure changes in expression of Wnt signaling pathway-related genes and osteogenesis-related molecules after osteogenesis induction. Alizarin red and ALP staining was used to confirm the osteogenic potential of stem cells. Bisulfite-specific PCR (BSP) was used to detect JKAMP methylation degree. Results Expression of JKAMP and osteogenesis-related molecules (RUNX2 and OPN) in DOP-ASCs was decreased significantly in comparison with CON-ASCs. JKAMP silencing inhibited the Wnt signaling pathway and reduced the osteogenic ability of CON-ASCs. Overexpression of JKAMP in DOP-ASCs rescued the impaired osteogenic capacity caused by DOP. Moreover, JKAMP in DOP-ASCs contained intragenic DNA hypermethylated regions related to the downregulation of JKAMP expression. Conclusions Intragenic DNA methylation inhibits the osteogenic ability of DOP-ASCs by suppressing expression of JKAMP and the Wnt signaling pathway. This study shows an epigenetic explanation for the reduced osteogenic ability of DOP-ASCs and provides a potential therapeutic target to prevent and treat osteoporosis.

Abstract Guided bone regeneration (GBR) is an effective and simple method for bone augmentation, which is often used to reconstruct the alveolar ridge when the bone defect occurs in the implant area. Titanium mesh has expanded the indications of GBR technology due to its excellent mechanical properties and biocompatibility, so that the GBR technology can be used to repair alveolar ridges with larger bone defects, and can obtain excellent and stable bone augmentation results. Currently, GBR with titanium mesh has various clinical applications, including different clinical procedures. Bone graft materials, titanium mesh covering methods, and titanium mesh fixing methods are also optional. Moreover, the research of GBR with titanium mesh has led to multifarious progresses in digitalization and material modification. This article reviews the properties of titanium mesh and the difference of titanium mesh with other barrier membranes; the current clinical application of titanium mesh in bone augmentation; common complications and management and prevention methods in the application of titanium mesh; and research progress of titanium mesh in digitization and material modification. Hoping to provide a reference for further improvement of titanium mesh in clinical application and related research of titanium mesh.

Abstract Bladder Cancer (BC) is the ninth most common tumor in the world and one of the most common malignant tumors of the urinary system. Some studies reported that miR‐133b expression is reduced in BC, but whether it plays a role in the development of BC and its mechanism is unclear. microRNAs can be packaged into exosomes to mediate communication between tumor cells, affecting their proliferation and apoptosis. The objective of this study was to investigate the effect of exosomal miR‐133b on BC proliferation and its molecular mechanism. Firstly, the expression of miR‐133b was evaluated in BC and adjacent normal tissues, as well as in serum exosomes of BC patients and healthy controls. Then the delivery and internalization of exosomes in cells was observed through fluorescence localization. Cell viability and apoptosis were assessed in BC cells transfected with mimics and incubated with exosomes. The role of exosomal miR‐133b was also analyzed in nude mice transplant tumors. Furthermore, the target gene of miR‐133b was predicted through bioinformatics. The level of miR‐133b was significantly decreased in BC tissues and in exosomes from serum of patients, which was correlated with poor overall survival in TCGA. Exosomal miR‐133b could be obtained using BC cells after transfection with miR‐133b mimics. The miR‐133b expression increased after incubation with exosomal miR‐133b, which lead to the inhibition of viability and increase of apoptosis in BC cells. Exosomal miR‐133b could suppress tumor growth in vivo. In addition, we found that exosomal miR‐133b may play a role in suppressing BC proliferation by upregulating dual‐specificity protein phosphatase 1 (DUSP1). These findings may offer promise for new therapeutic directions of BC.

Purposes: To investigate the effectiveness of a dichoptic optokinetic nystagmus (dOKN) test to objectively quantify interocular suppression in intermittent exotropia (IXT) patients during the states of orthotropia and exodeviation.Methods: The OKN motion in subjects (15 controls and 59 IXT subjects) who viewed dichoptic oppositely moving gratings with different contrast ratios was monitored and recorded by an eye tracker. Interocular suppression in control subjects was induced using neutral density (ND) filters. The OKN direction ratios were fitted to examine the changes of interocular suppression in subjects under different viewing states. Two established interocular suppression tests (phase and motion) were conducted for a comparative study.Results: The dOKN test, which requires a minimal response from subjects, could accurately quantify the interocular suppression in both IXT and control subjects, which is in line with the established interocular suppression tests. Overall, although comparative, the strength of interocular suppression detected by the dOKN test (0.171 ± 0.088) was stronger than those of the phase (0.293 ± 0.081) and the motion tests (0.212 ± 0.068) in the control subjects with 1.5 ND filters. In IXT patients, when their eyes kept aligned, the dOKN test (0.58 ± 0.09) measured deeper visual suppression compared with the phase (0.73 ± 0.17) or the motion test (0.65 ± 0.14). Interestingly, strong interocular suppression (dOKN: 0.15 ± 0.12) was observed in IXT subjects during the periods of exodeviation, irrespective of their binocular visual function as measured by synoptophore.Conclusion: The dOKN test provides efficient and objective quantification of interocular suppression in IXT, and demonstrates how it fluctuates under different eye positions.

Blue light is a major component of visible light and digital displays. Over-exposure to blue light could cause retinal damage. However, the mechanism of its damage is not well defined. Here, we demonstrate that blue light (900 lux) impairs cell viability and induces cell apoptosis in retinal neurocytes in vitro. A DNA electrophoresis assay shows severe DNA damage in retinal neurocytes at 2 h after blue light treatment. γ-H2AX foci, a specific marker of DNA double-strand breaks (DSBs), is mainly located in the Map2-posotive neuron other than the glia cell. After assaying the expression level of proteins related to DNA repair, Mre11, Ligase IV and Ku80, we find that Ku80 is up-regulated in retinal neurocytes after blue light treatment. Interestingly, Ku80 is mainly expressed in glia fibrillary acidic protein (GFAP)-positive glia cells. Moreover, following blue light exposure in vivo, DNA DSBs are shown in the ganglion cell layer and only observed in Map2-positive cells. Furthermore, long-term blue light exposure significantly thinned the retina in vivo. Our findings demonstrate that blue light induces DNA DSBs in retinal neurons, and the damage is more pronounced compared to glia cells. Thus, this study provides new insights into the mechanisms of the effect of blue light on the retina.

A traditional Chinese medicine, Tetramethylpyrazine (TMP), has been prescribed as a complementary treatment for glaucoma to improve patient prognosis. However, the pharmacological mechanism of action of TMP is poorly understood. In previous studies, we demonstrated that TMP exerts potent inhibitory effects on neovascularization, suppresses the tumorigenic behavior of glioma cells, and protects neural cells by regulating CXCR4 expression. Here, we further investigated whether the SDF-1/CXCR4 pathway is also involved in the TMP-mediated activity in trabecular meshwork cells.CXCR4 expression was examined by quantitative real-time PCR in trabecular and iris specimens from 54 primary open-angle glaucoma (POAG) patients who required surgery and 19 non-glaucomatous donors. Our data revealed markedly elevated CXCR4 expression in the trabecular meshwork of POAG patients compared with that of controls. Consistently, CXCR4 expression was much higher in glaucomatous trabecular meshwork cells than in normal trabecular meshwork cells. Using RT-PCR and western blot assays, we determined that glaucoma-related cytokines and dexamethasone (DEX) also significantly up-regulated CXCR4 expression in primary human trabecular meshwork (PHTM) cells. Moreover, the TGF-β1-mediated induction of CXCR4 expression in PHTM cells was markedly down-regulated by TMP compared with control treatment (PBS) and the CXCR4 antagonist AMD3100. In addition, TMP could counteract the TGF-β1-induced effects on stress fiber accumulation and expansion of PHTM cells. TMP markedly suppressed the migration of PHTM cells stimulated by TGF-β1 in transwell and scratch wound assays. TMP also suppressed the extracellular matrix (ECM) accumulation induced by TGF-β2.Our findings demonstrate that CXCR4 might be involved in the pathogenetic changes in the trabecular meshwork of patients with POAG. Additionally, TMP might exert its beneficial effects in POAG patients by down-regulating CXCR4 expression.

BackgroundTetramethylpyrazine (TMP) is one of the active ingredients extracted from the Chinese herb Chuanxiong, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer. However, the molecular mechanisms underlying the actions of TMP have not been fully elucidated. In a previous study we showed that TMP-mediated glioma suppression and neural protection involves the inhibition of CXCR4 expression. The SDF-1/CXCR4 axis plays a fundamental role in many physiological and pathological processes. In this study, we further investigated whether the regulation of the SDF-1/CXCR4 pathway is also involved in the TMP-mediated inhibition of neovascularization or fibrosis and improvement of microcirculation.Methodology/principal findingsUsing a scratch-wound assay, we demonstrated that TMP significantly suppressed the migration and tubule formation of the human umbilical vein endothelial cell line ECV304 in vitro. The expression of CXCR4 in ECV304 cells is notably down-regulated after TMP treatment. In addition, TMP significantly suppresses corneal neovascularization in a rat model of corneal alkali burn injury. The expression of CXCR4 on days 1, 3 and 7 post-injury was determined through RT-PCR analysis. Consistent with our hypotheses, the expression of CXCR4 in the rat cornea is significantly increased with alkali burn and dramatically down-regulated with TMP treatment. Moreover, TMP treatment significantly attenuates bleomycin-induced rat pulmonary fibrosis, while immunofluorescence shows a notably decreased amount of CXCR4-positive cells in the TMP-treated group. Furthermore, TMP significantly down-regulates the expression of CXCR4 in platelets, lymphocytes and red blood cells. Whole-blood viscosity and platelet aggregation in rats are significantly decreased by TMP treatment.ConclusionsThese results show that TMP exerts potent effects in inhibiting neovascularization, fibrosis and thrombosis under pathological conditions; thus, the underlying mechanism of TMP might partially contribute to the down-regulation of CXCR4.

Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression profile of BRCA1 in the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our data show the expression of BRCA1 is developmentally down-regulated in the retinas of mice after birth. Similarly, BRCA1 is down-regulated after differentiation induced by TSA in retinal precursor cells. An end-joining activity assay and DNA fragmentation analysis indicated that the DNA repair capacity is significantly reduced. Moreover, DNA damage in differentiated cells or cells in which BRCA1 is silenced by siRNA interference is more extensive than that in precursor cells subjected to ionizing radiation. To further investigate non-homologous end joining (NHEJ), the major repair pathway in non-divided neurons, we utilized an NHEJ substrate (pEPI-NHEJ) in which double strand breaks are generated by I-SceI. Our data showed that differentiation and the down-regulation of BRCA1 respectively result in a 2.39-fold and 1.68-fold reduction in the total NHEJ frequency compared with that in cells with normal BRCA1. Furthermore, the analysis of NHEJ repair junctions of the plasmid substrate indicated that BRCA1 is involved in the fidelity of NHEJ. In addition, as expected, the down-regulation of BRCA1 significantly inhibits the viability of retina precursor cells. Therefore, our data suggest that BRCA1 plays a critical role in retinal development and repairs DNA damage of mature retina neurocytes.

Purpose: To describe a novel digital design technique for creating an individualized emergence profile for implant restoration based on the contralateral tooth. Methods: Cone beam computed tomography (CBCT) data were used to accurately obtain a three-dimensional (3D) model of the contralateral tooth, which was mirror-flipped to design the emergence profile. The emergence profile was further divided into critical and subcritical areas; the critical area precisely replicated the mirror-flipped 3D model, whereas the subcritical area featured a slight concavity on the buccal side, flatness on the lingual side, and slight convexity on the mesial and distal surfaces. Subsequently, a milling machine was used to fabricate healing abutments with individualized emergence profiles. The design of the definitive restoration completely duplicated the emergence profile of the individualized healing abutment and was fabricated using a milling machine. Conclusions: This technical procedure presents an alternative novel method for designing the emergence profiles of implant restorations, with the potential to improve esthetics and functions as well as to maintain the long-term stability of peri-implant soft and hard tissues. [ABSTRACT FROM AUTHOR]

Patient: A 67-year-old woman presented with severe periodontitis-induced terminal dentition and proclined maxillary incisor. Three-dimensional facial esthetics-driven computer-assisted virtual tooth rearrangement was performed for implant-supported full-arch reconstruction. The digital workflow combines facial and spiral computed tomography (CT) scans to generate a virtual patient for three-dimensional (3D) facial analysis and obtain a visual treatment objective (VTO)- based lateral esthetic preview for virtual teeth rearrangement. Subsequently, this printed interim denture performed well in functionalization and esthetics, acted as a transitional removable denture, radiological template, and implant-supported interim denture, and guided the design of the final restoration. Discussion: Conventional methods for lateral esthetic preview, such as traditional wax rim try-in, confront difficulties in the treatment of terminal dentition, especially in the presence of proclined maxillary incisors. However, currently available software that aids information fusion and facial analysis can accurately predict soft-to-hard tissue movement and efficiently guide virtual tooth rearrangement for implant-supported full-arch reconstruction. Conclusions: The use of VTO-based lateral esthetic preview for implant-supported reconstruction improves pre- and postoperative information transfer accuracy and doctor-patient communication efficiency. [ABSTRACT FROM AUTHOR]