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Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and high-quality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (ß: -0.1, 95 % CI: -0.15, -0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (ß range: -0.2 â¼ -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.
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PURPOSE: In recent years, the use of deep learning for medical image segmentation has become a popular trend, but its development also faces some challenges. Firstly, due to the specialized nature of medical data, precise annotation is time-consuming and labor-intensive. Training neural networks effectively with limited labeled data is a significant challenge in medical image analysis. Secondly, convolutional neural networks commonly used for medical image segmentation research often focus on local features in images. However, the recognition of complex anatomical structures or irregular lesions often requires the assistance of both local and global information, which has led to a bottleneck in its development. Addressing these two issues, in this paper, we propose a novel network architecture. METHODS: We integrate a shift window mechanism to learn more comprehensive semantic information and employ a semi-supervised learning strategy by incorporating a flexible amount of unlabeled data. Specifically, a typical U-shaped encoder-decoder structure is applied to obtain rich feature maps. Each encoder is designed as a dual-branch structure, containing Swin modules equipped with windows of different size to capture features of multiple scales. To effectively utilize unlabeled data, a level set function is introduced to establish consistency between the function regression and pixel classification. RESULTS: We conducted experiments on the COVID-19 CT dataset and DRIVE dataset and compared our approach with various semi-supervised and fully supervised learning models. On the COVID-19 CT dataset, we achieved a segmentation accuracy of up to 74.56%. Our segmentation accuracy on the DRIVE dataset was 79.79%. CONCLUSIONS: The results demonstrate the outstanding performance of our method on several commonly used evaluation metrics. The high segmentation accuracy of our model demonstrates that utilizing Swin modules with different window sizes can enhance the feature extraction capability of the model, and the level set function can enable semi-supervised models to more effectively utilize unlabeled data. This provides meaningful insights for the application of deep learning in medical image segmentation. Our code will be released once the manuscript is accepted for publication.
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OBJECTIVE: To compare bone volume and height changes of two types of deproteinized bovine bone mineral (DBBM) for lateral window sinus floor elevation (LSFE) with simultaneous implant placement. MATERIALS AND METHODS: This retrospective cohort study involved 72 patients who underwent LSFE using low-temperature sintered cancellous bone-derived DBBM (C-DBBM) or high-temperature two-step sintered epiphyseal-derived DBBM (E-DBBM). Cone-beam computed tomography (CBCT) was acquired preoperatively, immediately postoperatively, 6 months and 1-4 years post-surgery. Bone volume (BV), apical bone height (ABH), endo-sinus bone gain (ESBG), and crestal bone level (CBL) were evaluated through three-dimensional fitting and superimposition. Linear mixed models (LMM) were employed to analyze factors influencing the reduction of BV (ΔBV) and ESBG (ΔESBG). RESULTS: The E-DBBM group showed no significant change in BV 1-4 years post-surgery, while the C-DBBM group demonstrated a significant reduction (p = .006) with volume stability of 85.86%. Bone height in the E-DBBM group increased at 6 months and subsequently decreased at 1-4 years (p = .003). In the C-DBBM group, it decreased at 6 months (p = .014), then further decreased at 1-4 years (p = .001). ΔESBG was lower in the E-DBBM group than the C-DBBM group from immediate postoperative to 1-4 years (p = .009). LMM showed graft material type was the primary factor influencing ΔBV (p = .026) and ΔESBG (p = .003). CONCLUSIONS: Within the limitations of this study, both types of DBBM could achieve favorable clinical outcomes. E-DBBM demonstrated enhanced stability in maintaining bone volume and height.
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OBJECTIVES: To assess the impact of a two-piece abutment workflow on enhancing the stability of the alveolar bone and gingiva surrounding the dental implant, and to determine the level of patient satisfaction. MATERIALS AND METHODS: A total of 48 patients with dentition defect in the posterior region were included and divided into two groups: the two-piece abutment workflow (TAW) and the sealing screw with submerged healing workflow (SHW). Marginal bone level (MBL), soft tissue indicators, oral hygiene indicators, and patient satisfaction were assessed and recorded partially at 0, 3, 6, and 12 months after surgery. The primary outcome was the change of MBL in different time periods. A generalized linear mixed model (GLMM) was used to take into account the correlated nature of the data, and adjust for potential confounding factors within inter-group differences. RESULTS: The survival rate of implants and prosthesis reached 100% at 12-month follow-up, with an average decrease of 0.25 mm (SD 0.23 mm) of MBL in the TAW group and 0.48 mm (SD 0.45 mm) in the SHW group. The change of MBL in the TAW group (0.15 ± 0.31 mm) was significantly lower than the SHW group (0.41 ± 0.41 mm) through the analysis of GLMM within 6 months, while no significance was found in 12 months. Moreover, less gingival pain and oppression during prosthesis loading, and less time consumption overall duration were showed in the TAW group through Visual Analogue Scale (VAS, p < 0.05). CONCLUSIONS: Within a 6-month period, the two-piece abutment workflow showed superior efficacy in preserving the integrity of the marginal bone level. Furthermore, it streamlined treatment procedures and mitigated discomfort, hence increasing patient satisfaction.
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Projeto do Implante Dentário-Pivô , Satisfação do Paciente , Humanos , Projetos Piloto , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Dente Suporte , Perda do Osso Alveolar , Resultado do Tratamento , Implantação Dentária Endóssea/métodosRESUMO
Air pollution is widely acknowledged as a significant risk factor for human health, especially reproductive health. Nevertheless, many studies have disregarded the potentially mixed effects of air pollutants on reproductive outcomes. We performed a retrospective cohort study involving 8048 women with 9445 cycles undergoing In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) in China, from 2017 to 2021. A land-use random forest model was applied to estimate daily residential exposure to air pollutants, including sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and fine particulate matter (PM2.5). Individual and joint associations between air pollutants and oocyte-related outcomes of ART were evaluated. In 90 days prior to oocyte pick-up to oocyte pick-up (period A), NO2, O3 and CO was negatively associated with total oocyte yield. In the 90 days prior to oocyte pick-up to start of gonadotropin medication (Gn start, period B), there was a negative dose-dependent association of exposure to five air pollutants with total oocyte yield and mature oocyte yield. In Qgcomp analysis, increasing the multiple air pollutants mixtures by one quartile was related to reducing the number of oocyte pick-ups by -2.00â¯% (95â¯%CI: -2.78â¯%, -1.22â¯%) in period A, -2.62â¯% (95â¯%CI: -3.40 %, -1.84â¯%) in period B, and -0.98â¯% (95â¯%CI: -1.75â¯%, -0.21â¯%) in period C. During period B, a 1-unit increase in the WQS index of multiple air pollutants exposure was associated with fewer number of total oocyte (-1.27â¯%, 95â¯%CI: -2.16â¯%, -0.36â¯%) and mature oocyte (-1.42â¯%, 95â¯%CI: -2.41â¯%, -0.43â¯%). O3 and NO2 were major contributors with adverse effects on the mixed associations. Additionally, period B appears to be the susceptible window. Our study implies that exposure to air pollution adversely affects oocyte-related outcomes, which raises concerns about the potential adverse impact of air pollution on women's reproductive health.
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Poluentes Atmosféricos , Oócitos , Feminino , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Estudos Retrospectivos , Oócitos/efeitos dos fármacos , Adulto , China , Técnicas de Reprodução Assistida , Poluição do Ar/efeitos adversos , Ozônio , Material Particulado/toxicidade , Material Particulado/análise , Exposição Ambiental/efeitos adversos , Fertilização in vitro , Estudos de Coortes , Dióxido de Nitrogênio/análiseRESUMO
OBJECTIVES: The objective of this study is to analyze the clinical and radiographic outcomes of implant-supported fixed protheses with cantilever extensions (ISFPCs) in the partially edentulous anterior mandible. MATERIALS AND METHODS: Patients who received anterior mandible implant restoration between January 2016 and December 2021 were included. Patients with two, three, or four continuous missing teeth receiving adjacent implant supported single-unit crowns (ISSCs), ISFPCs, implant-supported fixed protheses without cantilever extensions (ISFPNs) were divided into groups: ISSC+ISSC, ISFPC, ISSC+ISFPC, three-unit ISFPN, ISFPC+ISFPC, or four-unit ISFPN, respectively. We recorded and evaluated survival rates, mechanical and biological complications, peri-implant marginal bone loss (MBL), esthetic outcomes, and patient perceptions. Statistical analysis was performed using linear mixed models (LMM). RESULTS: The study included 87 patients and 152 implants. No implant loss occurred during an average follow-up of 3.48 ± 1.85 years (range: 1-7 years). According to LMM models, prosthetic type had a statistically significant impact on MBL during follow-up periods, in favor of the ISFPC and ISFPC+ISFPC groups (0.16 ± 0.48 mm vs. 0.51 ± 0.49 mm, p = .034; 0.22 ± 0.49 mm vs. 0.60 ± 0.62 mm, p = .043, respectively). Mechanical and biological complications were relatively low and comparable. The four-unit ISFPC group had higher subjective esthetic scores compared with the ISSC+ISSC group (98.6 vs. 83.8, p < .05), and patients in the ISFPC+ISFPC group expressed greater satisfaction with cleanability than the ISFPN group (98.8 vs. 80.6). CONCLUSION: ISFPCs offer a highly predictable treatment option in the anterior mandible, characterized by high survival rates, and comparable complication rates, peri-implant bone stability and esthetics to adjacent ISSCs or ISFPNs.
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Leydig cell failure (LCF) caused by gene mutations leads to testosterone deficiency, infertility and reduced physical function. Adeno-associated virus serotype 8 (AAV8)-mediated gene therapy shows potential in treating LCF in the Lhcgr-deficient (Lhcgr-/-) mouse model. However, the gene-treated mice still cannot naturally sire offspring, indicating the modestly restored testosterone and spermatogenesis in AAV8-treated mice remain insufficient to support natural fertility. Recognizing this, we propose that enhancing gene delivery could yield superior results. Here, we screened a panel of AAV serotypes through in vivo transduction of mouse testes and identified AAVDJ as an impressively potent vector for testicular cells. Intratesticular injection of AAVDJ achieved markedly efficient transduction of Leydig cell progenitors, marking a considerable advance over conventional AAV8 vectors. AAVDJ-Lhcgr gene therapy was well tolerated and resulted in significant recovery of testosterone production, substantial improvement in sexual development, and remarkable restoration of spermatogenesis in Lhcgr-/- mice. Notably, this therapy restored fertility in Lhcgr-/- mice through natural mating, enabling the birth of second-generation. Additionally, this treatment led to remarkable improvements in adipose, muscle, and bone function in Lhcgr-/- mice. Collectively, our findings underscore AAVDJ-mediated gene therapy as a promising strategy for LCF and suggest its broader potential in addressing various reproductive disorders.
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Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (ß = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (ß = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: ß = 0.26, 95%CI: 0.01 - -0.51, Pinteraction = 0.047; progressive motility: ß = 0.64, 95%CI: 0.23 - 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.
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Benzofenonas , Disruptores Endócrinos , Ácidos Graxos Ômega-3 , Ácidos Graxos Insaturados , Masculino , Humanos , Sêmen , Análise do Sêmen , Disruptores Endócrinos/toxicidade , Teorema de Bayes , EspermatozoidesRESUMO
OBJECTIVES: Deep networks have been preliminarily studied in caries diagnosis based on clinical X-ray images. However, the performance of different deep networks on caries detection is still unclear. This study aims to comprehensively compare the caries detection performances of recent multifarious deep networks with clinical dentist level as a bridge. METHODS: Based on the self-collected periapical radiograph dataset in clinic, four most popular deep networks in two types, namely YOLOv5 and DETR object detection networks, and UNet and Trans-UNet segmentation networks, were included in the comparison study. Five dentists carried out the caries detection on the same testing dataset for reference. Key tooth-level metrics, including precision, sensitivity, specificity, F1-score and Youden index, were obtained, based on which statistical analysis was conducted. RESULTS: The F1-score order of deep networks is YOLOv5 (0.87), Trans-UNet (0.86), DETR (0.82) and UNet (0.80) in caries detection. A same ranking order is found using the Youden index combining sensitivity and specificity, which are 0.76, 0.73, 0.69 and 0.64 respectively. A moderate level of concordance was observed between all networks and the gold standard. No significant difference (p > 0.05) was found between deep networks and between the well-trained network and dentists in caries detection. CONCLUSIONS: Among investigated deep networks, YOLOv5 is recommended to be priority for caries detection in terms of its high metrics. The well-trained deep network could be used as a good assistance for dentists to detect and diagnose caries. CLINICAL SIGNIFICANCE: The well-trained deep network shows a promising potential clinical application prospect. It can provide valuable support to healthcare professionals in facilitating detection and diagnosis of dental caries.
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Cárie Dentária , Redes Neurais de Computação , Sensibilidade e Especificidade , Humanos , Cárie Dentária/diagnóstico por imagem , Aprendizado Profundo , Radiografia Interproximal , Radiografia Dentária/métodos , Processamento de Imagem Assistida por Computador/métodos , Odontólogos , Dente/diagnóstico por imagemRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells. To address this question, we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1 (ASGR1) promoted SARS-CoV-2 pseudovirus infection of HeLa cells. In Huh-7 cells, simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells, both of which barely expressed ACE2, SARS-CoV-2 pseudovirus could successfully establish an infection. However, after treatment with ASGR1 antibody or siRNA targeting ASGR1, the infection rate significantly dropped, suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism. We confirmed that ASGR1 could interact with Spike protein, which depends on receptor binding domain (RBD) and N-terminal domain (NTD). Finally, we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells. After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA, the infection efficiency of the live virus decreased significantly. Collectively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.
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COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/fisiologia , Receptor de Asialoglicoproteína/genética , Células HeLa , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/química , Hepatócitos , RNA Interferente PequenoRESUMO
BACKGROUND: Humans are exposed to various chemicals, including organophosphate esters (OPEs), phthalates (PAEs), and phenols. The effects on early reproductive outcomes of in vitro fertilization (IVF) remain unclear. METHODS: We recruited 192 women and 157 men who underwent IVF treatment. A total of forty-nine urinary chemicals were detected, including six OPEs, fifteen PAEs, six parabens, two chlorophenols, nine bisphenols, five benzophenones, and six synthetic phenolic antioxidants. We examined the individual and joint effects of parental chemical exposure on early reproductive outcomes. RESULTS: We found that certain chemicals were associated with early reproductive outcomes in Poisson regression models. For example, urinary diphenyl phosphate was negatively associated with high-quality embryos in both female (ß: -0.12, 95%CI: -0.17, -0.07) and male partners (ß: -0.09, 95%CI: -0.15, -0.03). A negative association was found between mixed chemicals and high-quality embryos in Bayesian kernel machine regression, weighted quantile sum regression (ß: -0.34, 95%CI: -0.60, -0.07), and quantile-based g-computation model (ß: -0.69, 95%CI: -1.34, -0.05) among female partners. Paternal mixture exposure was not associated with early reproductive outcomes. CONCLUSIONS: Our results indicated that increased exposure to environmental chemicals was associated with adverse early reproductive outcomes of IVF, especially female partners.
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Poluentes Ambientais , Exposição Materna , Humanos , Masculino , Feminino , Teorema de Bayes , Reprodução , Fertilização in vitro , Fenóis , Organofosfatos , Exposição AmbientalRESUMO
Fertilization is a complex and highly regulated process that involves a series of molecular interactions between sperm and oocytes. However, the mechanisms of proteins involved in human fertilization, such as that of testis-specific SPACA4, remain poorly understood. Here we demonstrated that SPACA4 is a spermatogenic cell-specific protein. SPACA4 is expressed during spermatogenesis, upregulated in early-stage spermatids, and downregulated in elongating spermatids. SPACA4 is an intracellular protein that locates in the acrosome and is lost during the acrosome reaction. Incubation with antibodies against SPACA4 inhibited the binding of spermatozoa to zona pellucida. SPACA4 protein expression levels across different semen parameters were similar but varied significantly among patients. A prospective clinical study found no association between SPACA4 protein levels and fertilization or cleavage rates. Thus, the study suggests a novel function for SPACA4 in human fertilization in a non-dose-dependent manner. However, a larger clinical trial is required to evaluate the potential use of sperm SPACA4 protein levels to predict fertilization potential.
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BACKGROUND: Preimplantation genetic testing (PGT) for monogenic disorders (PGT-M) for germline mosaicism was previously highly dependent on polymerase chain reaction (PCR)-based directed mutation detection combined with linkage analysis of short tandem repeats (STRs). However, the number of STRs is usually limited. In addition, designing suitable probes and optimizing the reaction conditions for multiplex PCR are time-consuming and laborious. Here, we evaluated the effectiveness of next generation sequencing (NGS)-based haplotype linkage analysis in PGT of germline mosaicism. METHODS: PGT-M with NGS-based haplotype linkage analysis was performed for two families with maternal germline mosaicism for an X-linked Duchenne muscular dystrophy (DMD) mutation (del exon 45-50) or an autosomal TSC1 mutation (c.2074C > T). Trophectoderm biopsy and multiple displacement amplification (MDA) were performed for a total of nine blastocysts. NGS and Sanger sequencing were performed in genomic DNA of family members and embryonic MDA products to detect DMD deletion and TSC1 mutation, respectively. Single nucleotide polymorphism (SNP) sites closely linked to pathogenic mutations were detected with NGS and served in haplotype linkage analysis. NGS-based aneuploidy screening was performed for all embryos to reduce the risk of pregnancy loss. RESULTS: All nine blastocytes showed conclusive PGT results. Each family underwent one or two frozen-thawed embryo transfer cycles to obtain a clinical pregnancy, and the prenatal diagnosis showed that the fetus was genotypically normal and euploid for both families. CONCLUSIONS: NGS-SNP could effectively realize PGT for germline mosaicism. Compared with PCR-based methods, the NGS-SNP method with increased polymorphic informative markers can achieve a greater diagnostic accuracy. Further studies are warranted to verify the effectiveness of NGS-based PGT of germline mosaicism cases in the absence of surviving offsprings.
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Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Diagnóstico Pré-Implantação/métodos , Mosaicismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Haplótipos/genética , Testes Genéticos/métodos , Células GerminativasRESUMO
OBJECTIVES: This study aimed to evaluate the survival rate of variable-thread tapered implants (VTTIs) and identify risk factors for early/late implant loss. MATERIALS AND METHODS: From January 2016 to December 2019, patients who received VTTIs were included in this study. The cumulative survival rates (CSRs) at implant/patient levels were calculated by the life table method and presented via Kaplan-Meier survival curves. The relation between investigated variables and early/late implant loss was analyzed by the multivariate generalized estimating equation (GEE) regression model on the implant level. RESULTS: A total of 1528 patients with 2998 VTTIs were included. 95 implants from 76 patients were lost at the end of observation. At the implant level, the CSRs at 1, 3, and 5 years were 98.77%, 96.97%, and 95.39%, respectively, whereas they were 97.84%, 95.31%, and 92.96% at the patient level, respectively. The multivariate analysis revealed that non-submerged implant healing (OR = 4.63, p = .037) was associated with the early loss of VTTIs. Besides, male gender (OR = 2.48, p = .002), periodontitis (OR = 3.25, p = .007), implant length <10 mm (OR = 2.63, p = .028), and overdenture (OR = 9.30, p = .004) could significantly increase the risk of late implant loss. CONCLUSION: Variable-thread tapered implants could reach an acceptable survival rate in clinical practice. Non-submerged implant healing was associated with early implant loss; male gender, periodontitis, implant length <10 mm, and overdenture would significantly increase the risk of late implant loss.
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Perda do Osso Alveolar , Implantes Dentários , Humanos , Masculino , Implantes Dentários/efeitos adversos , Falha de Restauração Dentária , Estudos Retrospectivos , Fatores de Risco , Estimativa de Kaplan-Meier , Implantação Dentária Endóssea/efeitos adversos , Implantação Dentária Endóssea/métodos , Perda do Osso Alveolar/etiologia , Planejamento de Prótese Dentária/efeitos adversos , Prótese Dentária Fixada por Implante/efeitos adversosRESUMO
OBJECTIVE: To evaluate the performance of the indirect technique in peri-implant soft tissue contour duplication after the delivery procedure in the anterior maxilla. MATERIALS AND METHODS: Patients with single implant-supported fixed restorations in the anterior maxilla were recruited. For the impression procedure, an intraoral scan was acquired by both the direct and the indirect techniques. For the delivery procedure, implants were randomly allocated into one of the two groups according to the approaches of digital impression preceding definite crown fabrication (A-direct technique; B-indirect technique) and were scanned again after the definite crown delivery. The stereolithography files were superimposed to analyze changes in peri-implant soft tissue contour after the delivery procedure. The main outcomes were dimensional deviations of peri-implant mucosa, and the secondary outcome was differences in the pink esthetic score (PES). RESULTS: A total of 20 implants that underwent the complete workflow were included. After the delivery procedure, significant deviations in palatal tissue thickness between the provisional and definite crowns were observed in Group A but these were absent in Group B. Additionally, deviations in labial thickness (0.27 ± 0.12 mm vs. 0.08 ± 0.09 mm) and palatal thickness (0.17 ± 0.15 mm vs. 0.03 ± 0.08 mm), and labial volume of soft tissue (1.87 ± 0.94 mm3 vs. 0.75 ± 0.74 mm3 ) in Group A were significantly higher than those in Group B. No significant differences in PES were found. CONCLUSION: The indirect technique of scanning the provisional crown can more accurately duplicate the peri-implant soft tissue contour than the direct technique, resulting in a smaller deviation of the soft tissue in the delivery procedure.
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Implantes Dentários para Um Único Dente , Maxila , Humanos , Maxila/diagnóstico por imagem , Maxila/cirurgia , Projetos Piloto , Estética Dentária , Implantação Dentária Endóssea/métodos , Coroas , Resultado do TratamentoRESUMO
OBJECTIVES: To radiographically analyze the effects of tenting screw technique (TS) and onlay bone grafts (OG) in horizontal bone augmentation. MATERIALS AND METHODS: Patients receiving horizontal bone augmentation by TS or OG were selected. The clinical outcomes and cone beam computed tomography (CBCT) data were documented pre-grafting, immediately post-grafting, before and after implantation. The survival rates, clinical complications, alveolar bone width, and volumetric bone augmentation were evaluated and statistically analyzed. RESULTS: A total of 25 patients and 41 implants were involved in this study, with no grafting failures observed in either the TS group (n = 20) or the onlay group (n = 21). Volumetric bone resorption rate in the TS group (21.34%) was significantly lower than that of the OG group (29.38%). In addition, significant horizontal bone gain was achieved in both groups (TS: 6.15 ± 2.12 mm; OG: 4.86 ± 1.40 mm) during the recovery period, with higher gain in the TS group. No apparent statistical difference in terms of volumetric bone gain was observed between the TS (748.53 mm3 , 607.47 mm3 ) and OG group (811.77 mm3 , 508.49 mm3 ) immediately post-grafting or after the recovery period. CONCLUSION: Both TS and OG achieved satisfactory bone augmentation effects, yet TS resulted in more bone augmentation and better stability than OG, with a reduced use of autogenous bone. Overall, the tenting screw technique can serve as an effective alternative to autogenous bone grafts.
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Aumento do Rebordo Alveolar , Implantes Dentários , Humanos , Implantação Dentária Endóssea , Estudos Retrospectivos , Aumento do Rebordo Alveolar/métodos , Parafusos Ósseos , Transplante Ósseo/métodosRESUMO
Chimeric antigen receptor (CAR)-T cells, a therapeutic agent for solid tumors, are not completely effective due to a lack of infiltration of T cells into the tumor site and immunity caused by Programmed Death Receptor 1(PD1). Here, an epidermal growth factor receptor (EGFR) CAR-T cell was engineered to express the chemokine receptor CCR6 and secrete PD1 blocking Single-chain antibody fragment (scFv) E27 to enhance their anti-tumor effects. The findings showed that CCR6 enhanced the migration of EGFR CAR-E27-CCR6 T cells in vitro by the Transwell migration assay. When incubated with tumor cells, EGFR CAR-E27-CCR6 T cells specifically exerted potent cytotoxicity and produced high levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interferon-γ (IFN-γ). A non-small cell lung carcinoma (NSCLC) cell line-derived xenograft model was constructed by implanting modified A549 cell lines into immunodeficient NOD.PrkdcscidIl2rgem1/Smoc (NSG) mice. In comparison with traditional EGFR CAR-T cells, live imaging indicated that EGFR CAR-E27-CCR6 T cells displayed superior anti-tumor function. In addition, the histopathological examination of mouse organs showed no obvious organic damage. Our findings confirmed that PD1 blocking and CCR6 can enhance the anti-tumor function of EGFR CAR-T cells in an NSCLC xenograft model, providing an effective treatment strategy to improve the efficacy of CAR-T in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores de Antígenos Quiméricos , Animais , Humanos , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Imunoterapia Adotiva/métodos , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos NOD , Receptores CCR6 , Receptores de Quimiocinas , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor de Morte Celular Programada 1/metabolismoRESUMO
HIV-specific chimeric antigen receptor (CAR) T-cells have been developed to target HIV-1 infected CD4+ T-cells that express HIV Env proteins. However, T cell exhaustion and the patient-specific autologous paradigm of CAR-T cell hurdled clinical applications. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 (3BE) CAR construct that enabled the expression of programmed cell death protein (PD-1) -blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV Env. Compared with T cells expressing 3BNC117-CAR alone, 3BE CAR-T cells showed greater cytotoxic activity against HIV Env+ cells with stronger proliferation capability, higher killing efficiency, and enhanced cytokine secretion in the presence of HIV Env-expressing cells. Furthermore, we manufactured TCR-deficient 3BE CAR-T cells through gene editing and demonstrated that these CAR-T cells could effectively kill HIV Env â+ âcells in vivo without the occurrence of severe graft-versus-host disease (GvHD) in NSG mice. These data suggest that we have provided a feasible approach to the generation of "off-the-shelf" anti-HIV CAR-T cells in combination with PD-1 checkpoint blockade immunotherapy, which can be a powerful therapeutic candidate for the functional cure of HIV.
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Transplante de Células-Tronco Hematopoéticas , Receptor de Morte Celular Programada 1 , Humanos , Animais , Camundongos , Leucócitos Mononucleares , Edição de Genes , Linfócitos TRESUMO
PURPOSE: To analyze the marginal bone loss (ΔMBL) of tissue- or bone-level implants after placed with simultaneous guided bone regeneration (GBR). MATERIALS AND METHODS: A total of 151 patients who received 104 tissue-level or 128 bone-level implants placement with simultaneous GBR in the mandibular posterior region between January 2011 and December 2016 were included in this study. The marginal bone level (MBL) was recorded using the radiographic data obtained at implant placement, second-stage surgery, and the follow-up visit. Generalized estimating equation (GEE) was used to compare the ΔMBL of tissue- and bone-level implants, and the influencing factors of ΔMBL were further analyzed. RESULTS: At the last follow-up visit, the MBL of tissue-level implants was 0.73 ± 0.86 mm, above the rough-smooth interface, while that of bone-level implants was 0.82 ± 1.05 mm, above the implant platform. The ΔMBL of tissue-level implants was 1.03 mm, which was slightly higher than 0.81 mm of bone-level implants, but there was no significant difference (p > 0.05). No contributing factor associated with ΔMBL was identified by multivariate regression analysis in this study. CONCLUSION: Within the limits of this retrospective analysis, the ΔMBL of tissue-level implants is similar to that of bone-level implants after placed with simultaneous GBR, and both types of implants can achieve desirable marginal bone stability.
Assuntos
Perda do Osso Alveolar , Implantes Dentários , Humanos , Implantação Dentária Endóssea , Estudos Retrospectivos , Resultado do Tratamento , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/cirurgia , Regeneração ÓsseaRESUMO
BACKGROUND: Luteinizing hormone (LH) can stimulate mural granulosa cells to produce Amphiregulin (AREG), which can induce the resumption of meiosis in oocytes. Theca cells are present in the outer layer of follicles, providing communication with the pituitary axis through the established vascular system around the follicle. As LH target cells, it is unknown whether theca cells can produce AREG after LH stimulation. METHODS: Primary cultured human theca cells were treated with LH (with or without the inhibitor of PKA, H89), or agonists of adenylate cyclase (forskolin or db-cAMP). The mRNA and protein levels of AREG were evaluated by RT-qPCR, immunochemistry, immunofluorescence, western blotting, and ELISA. RESULTS: Immunohistochemistry of normal ovarian tissue obtained in the early-mid follicle phase showed that AREG expression was absent in both the theca layer and the granulosa cell layer of antral follicles. Double immunofluorescent staining revealed colocalization of AREG and CYP17A1 in human theca cells and colocalization of FSHR and AREG in human granulosa cells isolated from follicular fluid collected during IVF/ICSI after hCG trigger. LH significantly increased the mRNA and protein levels of AREG in human theca cells and the concentration of AREG in the culture medium. Forskolin and db-cAMP, activators of the cAMP/PKA signalling pathway, also significantly increased the mRNA and protein levels of AREG in human theca cells and the concentration of AREG in the culture medium. H89 antagonized the stimulating effect of LH on AREG expression in human theca cells. In addition, the concentration of AREG was lower in polycystic ovarian syndrome (PCOS) follicular fluid than in normal follicular fluid. The mRNA levels of AREG were significantly lower in PCOS granulosa cells and theca cells than in normal granulosa cells and theca cells. CONCLUSION: LH can stimulate the expression of AREG in human theca cells, and the adenylate cyclase/cAMP/PKA cascade may mediate this process. Expression of AREG is decreased in PCOS theca cells compared to normal theca cells, with or without LH stimulation.