Search

Abstract Background The determining effect of facial hard tissues on soft tissue morphology in orthodontic patients has yet to be explained. The aim of this study was to clarify the hard-soft tissue relationships of the lower 1/3 of the face in skeletal Class II-hyperdivergent patients compared with those in Class I-normodivergent patients using network analysis. Methods Fifty-two adult patients (42 females, 10 males; age, 26.58 ± 5.80 years) were divided into two groups: Group 1, 25 subjects, skeletal Class I normodivergent pattern with straight profile; Group 2, 27 subjects, skeletal Class II hyperdivergent pattern with convex profile. Pretreatment cone-beam computed tomography and three-dimensional facial scans were taken and superimposed, on which landmarks were identified manually, and their coordinate values were used for network analysis. Results (1) In sagittal direction, Group 2 correlations were generally weaker than Group 1. In both the vertical and sagittal directions of Group 1, the most influential hard tissue landmarks to soft tissues were located between the level of cemento-enamel junction of upper teeth and root apex of lower teeth. In Group 2, the hard tissue landmarks with the greatest influence in vertical direction were distributed more forward and downward than in Group 1. (2) In Group 1, all the correlations for vertical-hard tissue to sagittal-soft tissue position and sagittal-hard tissue to vertical-soft tissue position were positive. However, Group 2 correlations between vertical-hard tissue and sagittal-soft tissue positions were mostly negative. Between sagittal-hard tissue and vertical-soft tissue positions, Group 2 correlations were negative for mandible, and were positive for maxilla and teeth. Conclusion Compared with Class I normodivergent patients with straight profile, Class II hyperdivergent patients with convex profile had more variations in soft tissue morphology in sagittal direction. In vertical direction, the most relevant hard tissue landmarks on which soft tissue predictions should be based were distributed more forward and downward in Class II hyperdivergent patients with convex profile. Class II hyperdivergent pattern with convex profile was an imbalanced phenotype concerning sagittal and vertical positions of maxillofacial hard and soft tissues.

Abstract Background Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide with major prevalence in the developing countries and can cause extrahepatic disease including the nervous system. Central nervous system infections caused by HEV are rare and caused by HEV together with other bacteria are even rarer. Case presentation A 68-year-old man was admitted to the hospital due to a headache lasting for 6 days and a fever for 3 days. Lab tests showed significantly raised indicators of inflammation, cloudy cerebrospinal fluid, and liver dysfunction. Hepatitis E virus and Klebsiella pneumoniae were identified in the blood and cerebrospinal fluid using metagenomic next-generation sequencing. The patient received meropenem injection to treat K. pneumoniae infection, isoglycoside magnesium oxalate injection and polyene phosphatidylcholine injection for liver protection. After ten days of treatment, the patient improved and was discharged from the hospital. Conclusion Metagenomic next-generation sequencing, which can detect various types of microorganisms, is powerful for identifying complicated infections.

Abstract Objectives This study aimed to investigate vertical changes in the maxillary central incisor and the maxillary first molar, along with alterations in the mandibular plane angle during space closure using miniscrew sliding mechanics. Methods Twenty adult patients treated at Peking University Hospital of Stomatology between 2008 and 2013 were included. Digital dental models and craniofacial cone-beam computed tomography (CBCT) scans were obtained at the start of treatment (T0) and immediately after space closure (T1). Stable miniscrews were used for superimposing maxillary digital dental models (T0 and T1), and vertical changes in the maxillary first molar and the maxillary central incisor were measured. Three-dimensional changes in the mandibular plane were assessed through CBCT superimposition. Results The maxillary central incisor exhibited an average extrusion of 2.56 ± 0.18 mm, while the maxillary first molar showed an average intrusion of 1.25 ± 1.11 mm with a distal movement of 0.97 ± 0.99 mm. Additionally, the mandibular plane angle decreased by an average of 0.83 ± 1.65°. All three indices exhibited statistically significant differences. Conclusion During space closure using the miniscrew sliding technique, significant changes occurred in both the sagittal and vertical dimensions of the upper dentition. This included extrusion of the maxillary central incisors, intrusion of the maxillary first molars, and a slight counterclockwise rotation of the mandibular plane.

Advanced periodontitis poses a significant threat to oral health, causing extensive damage and loss of both hard and soft periodontal tissues. While traditional therapies such as scaling and root planing can effectively halt the disease’s progression, they often fail to fully restore the original architecture and function of periodontal tissues due to the limited capacity for spontaneous regeneration. To address this challenge, periodontal tissue engineering has emerged as a promising approach. This technology centers on the utilization of biomaterial scaffolds, which function as three-dimensional (3D) templates or frameworks, supporting and guiding the regeneration of periodontal tissues, including the periodontal ligament, cementum, alveolar bone, and gingival tissue. These scaffolds mimic the extracellular matrix (ECM) of native periodontal tissues, aiming to foster cell attachment, proliferation, differentiation, and, ultimately, the formation of new, functional periodontal structures. Despite the inherent challenges associated with preclinical testing, the intensification of research on biomaterial scaffolds, coupled with the continuous advancement of fabrication technology, leads us to anticipate a significant expansion in their application for periodontal tissue regeneration. This review comprehensively covers the recent advancements in biomaterial scaffolds engineered specifically for periodontal tissue regeneration, aiming to provide insights into the current state of the field and potential directions for future research.

Abstract Background Assessment of growth-related or treatment-related changes in the maxilla requires a reliable method of superimposition. Such methods are well established for two-dimensional (2D) cephalometric images but not yet for three-dimensions (3D). The aims of this study were to identify natural reference structures (NRS) for the maxilla in growing patients in 3D, opportunistically using orthodontic mini-screws as reference; and to test the applicability of the proposed NRS for maxillary superimposition by assessing the concordance of this approach with Björk’s ‘stable reference structures’ in lateral projection. Methods The stability of the mini-screws was tested on longitudinal pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images by measuring the distance changes between screws. After verifying the stability of the mini-screws, rigid registration was performed for aligning the stable mini-screws. Then, non-rigid registration was used to establish the dense voxel-correspondence among CBCT images and calculate the displacement of each voxel belonging to the maxilla relative to the mini-screws. The displacement vectors were transformed to a standardized maxillary template to categorize the stability of the internal structures statistically. Those voxels that displaced less relative to the mini-screws were considered as the natural reference structures (NRS) for the maxilla. Test samples included another dataset of longitudinal CBCT scans. They were used to evaluate the applicability of the proposed NRS for maxillary superimposition. We assessed whether aligning the maxilla with proposed NRS is in concordance with the maxillary internal reference structures superimposition in the traditional 2D lateral view as suggested by Björk. This was quantitively assessed by comparing the mean sagittal and vertical tooth movements for both superimposition methods. Results The stability of the mini-screws was tested on 10 pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images (T1: 12.9 ± 0.8 yrs, T2: 14.8 ± 0.7 yrs). Both the loaded and the unloaded mini-screws were shown to be stable during orthodontic treatment, which indicates that they can be used as reference points. By analyzing the deformation map of the maxilla, we confirmed that the infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than 1 cm distal to incisor foramen except the palatal suture) were stable during growth. Another dataset of longitudinal CBCT scans (T1: 12.2 ± 0.63 yrs, T2: 15.2 ± 0.96 yrs) was used to assess the concordance of this approach with Björk’s ‘stable reference structures’. The movement of the maxillary first molar and central incisor showed no statistically significant difference when superimposing the test images with the proposed NRS or with the classic Björk maxillary superimposition in the lateral view. Conclusions The infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than 1 cm posterior to incisal foramen except the palatal suture) were identified as stable regions in the maxilla. These stable structures can be used for maxillary superimposition in 3D and generate comparable results to Björk superimposition in the lateral view.

Abstract Background FAT4 (FAT Atypical Cadherin 4) is a member of the cadherin-associated protein family, which has been shown to function as a tumor suppressor by inhibiting proliferation and metastasis. The Wnt/β-catenin pathway activation is highly associated with PD-L1-associated tumor immune escape. Here, we report the mechanism by which FAT4 overexpression regulates anti-tumor immunity in cervical cancer by inhibiting PD-L1 N-glycosylation and cell membrane localization in a β-catenin-dependent manner. Methods FAT4 expression was first detected in cervical cancer tissues and cell lines. Cell proliferation, clone formation, and immunofluorescence were used to determine the tumor suppressive impact of FAT4 overexpression in vitro, and the findings were confirmed in immunodeficient and immunocomplete mice xenografts. Through functional and mechanistic experiments in vivo and in vitro, we investigated how FAT4 overexpression affects the antitumor immunity via the β-catenin/STT3/PD-L1 axis. Results FAT4 is downregulated in cervical cancer tissues and cell lines. We determined that FAT4 binds to β-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of β-catenin by the degradation complexes (AXIN1, APC, GSK3β, CK1). FAT4 overexpression decreases programmed death-ligand 1 (PD-L1) mRNA expression at the transcriptional level, and causes aberrant glycosylation of PD-L1 via STT3A at the post-translational modifications (PTMs) level, leading to its endoplasmic reticulum (ER) accumulation and polyubiquitination-dependent degradation. We found that FAT4 overexpression promotes aberrant PD-L1 glycosylation and degradation in a β-catenin-dependent manner, thereby increasing cytotoxic T lymphocyte (CTL) activity in immunoreactive mouse models. Conclusions These findings address the basis of Wnt/β-catenin pathway activation in cervical cancer and provide combination immunotherapy options for targeting the FAT4/β-catenin/STT3/PD-L1 axis. Graphical Abstract Schematic cartoons showing the antitumor immunity mechanism of FAT4. (left) when Wnts bind to their receptors, which are made up of Frizzled proteins and LRP5/6, the cytoplasmic protein DVL is activated, inducing the aggregation of degradation complexes (AXIN, GSK3β, CK1, APC) to the receptor. Subsequently, stable β-catenin translocates into the nucleus and binds to TCF/LEF and TCF7L2 transcription factors, leading to target genes transcription. The catalytically active subunit of oligosaccharyltransferase, STT3A, enhances PD-L1 glycosylation, and N-glycosylated PD-L1 translocates to the cell membrane via the ER-to-Golgi pathway, resulting in immune evasion. (Right) FAT4 exerts antitumor immunity mainly through following mechanisms: (i) FAT4 binds to β-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of β-catenin by the degradation complexes (AXIN1, APC, GSK3β, CK1); (ii) FAT4 inhibits PD-L1 and STT3A transcription in a β-catenin-dependent manner and induces aberrant PD-L1 glycosylation and ubiquitination-dependent degradation; (iii) Promotes activation of cytotoxic T lymphocytes (CTL) and infiltration into the tumor microenvironment.

Previous studies have shown that the risk of malignant transformation of endometriosis in premenopausal women is approximately 1%, significantly impacting the overall well-being and quality of life of affected women. Presently, the diagnostic gold standard for endometriosis-associated ovarian cancer (EAOC) continues to be invasive laparoscopy followed by histological examination. However, the application of this technique is limited due to its high cost, highlighting the importance of identifying a non-invasive diagnostic approach. Therefore, there is a critical need to explore non-invasive diagnostic methods to improve diagnostic precision and optimize clinical outcomes for patients. This review presents a comprehensive survey of the current progress in comprehending the pathogenesis of malignant transformation in endometriosis. Furthermore, it examines the most recent research discoveries concerning the diagnosis of EAOC and emphasizes potential targets for therapeutic intervention. The ultimate objective is to improve prevention, early detection, precise diagnosis, and treatment approaches, thereby optimizing the clinical outcomes for patients.

IntroductionInfectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples.MethodsIn this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform–based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios.ResultsCombined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii.DiscussionRapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

Ovarian cancer affects the female reproductive system and is the primary cause of cancer related mortality globally. The imprecise and non-specific nature of ovarian cancer symptoms often results in patients being diagnosed at an advanced stage, with metastatic lesions extending beyond the ovary. This presents a significant clinical challenge and imposes a substantial economic burden on both patients and society. Despite advancements in surgery, chemotherapy, and immunotherapy, the prognosis for most patients with ovarian cancer remains unsatisfactory. Therefore, the development of novel treatment strategies is imperative. Ferroptosis, a distinct form of regulated cell death, characterized by iron-dependent lipid peroxidation, differs from autophagy, apoptosis, and necrosis, and may hold promise as a novel cell death. Numerous studies have demonstrated the involvement of ferroptosis in various conventional signaling pathways and biological processes. Recent investigations have revealed the significant contribution of ferroptosis in the initiation, progression, and metastasis of diverse malignant tumors, including ovarian cancer. Moreover, ferroptosis exhibits a synergistic effect with chemotherapy, radiotherapy, and immunotherapy in restraining the proliferation of ovarian cancer cells. The aforementioned implies that ferroptosis holds considerable importance in the management of ovarian cancer and has the potential to serve as a novel therapeutic target. The present review provides a comprehensive overview of the salient features of ferroptosis, encompassing its underlying mechanisms and functional role in ovarian cancer, along with the associated signaling pathways and genes. Furthermore, the review highlights the prospective utility of ferroptosis in the treatment of ovarian cancer.

We report a case of a woman with diabetes mellitus and choledocholithiasis who had a low fever with chills and severe weakness for 7 days. The patient’s abdominal tenderness was positive. Computed tomography and magnetic resonance imaging showed a giant abscess in the liver. The production of extended-spectrum β-lactamases by hypervirulent Klebsiella pneumoniae was found in the purulent fluid of the liver by nanopore-based metagenomic third-generation sequencing combined with an antibiotic susceptibility test. The patient recovered after intravenous antibiotic therapy and percutaneous drainage. Patients with a history of diabetes mellitus and choledocholithiasis should be aware of the possibility of pyogenic liver abscesses caused by hypervirulent Klebsiella pneumoniae . To rapidly control the development of this disease, nanopore-based metagenomic third-generation sequencing plays an important role not only in rapidly identifying pathogens, but also in guiding the use of antibiotics.

Abstract Background To establish the digital diagnostic templates by cluster analysis based on a set of cephalometric films and evaluate the outcome of the different treatment methods in the patients affiliated to the same cephalometric morphology template (CMT). These templates could be used for the automatic diagnosis of dentofacial deformities and prediction of treatment outcomes in the future. Methods In this study, we assessed the coordinates of 60 different landmarks on the cephalograms of 2249 patients (14.35 ± 4.99 years, range from 7 to 62) with dentofacial deformities. The cephalometric data were subjected to dentist for clustering without a priori pattern definitions to generate biologically informative CMTs. Three templates were selected to evaluate the treatment outcome of patients affiliated to the same CMT. Results The cluster analysis yielded 21 distinct groups. The total discriminant accuracy was 89.1%, while the cross-validation accuracy was 85.0%, showing that the clusters were robust. All CMTs were automatically created and drawn using a computer, based on the average coordinates of each cluster. Individuals affiliated to the same CMT showed similar dentofacial features. We also evaluated differences in the outcomes of patients affiliated to the same CMT. Conclusions Our results demonstrated the utility of clustering methods for grouping dentofacial deformities with similar dentofacial features. Clustering methods can be used to evaluate the differences in the outcomes of patients affiliated to the same CMT, which has good clinical application value.

Despite advances in cervical cancer screening and human papilloma virus (HPV) vaccines, cervical cancer remains a global health burden. The standard treatment of cervical cancer includes surgery, radiation therapy, and chemotherapy. Radiotherapy (RT) is the primary treatment for advanced-stage disease. However, due to radioresistance, most patients in the advanced stage have an adverse outcome. Recent studies have shown that long noncoding RNAs (lncRNAs) participate in the regulation of cancer radiosensitivity by regulating DNA damage repair, apoptosis, cancer stem cells (CSCs), and epithelial–mesenchymal transition (EMT). In this review, we summarize the molecular mechanisms of long noncoding RNAs in cervical cancer and radiosensitivity, hoping to provide a theoretical basis and a new molecular target for the cervical cancer RT in the clinic.

Abstract This paper presents an unsupervised clustering random-forest-based metric for affinity estimation in large and high-dimensional data. The criterion used for node splitting during forest construction can handle rank-deficiency when measuring cluster compactness. The binary forest-based metric is extended to continuous metrics by exploiting both the common traversal path and the smallest shared parent node. The proposed forest-based metric efficiently estimates affinity by passing down data pairs in the forest using a limited number of decision trees. A pseudo-leaf-splitting (PLS) algorithm is introduced to account for spatial relationships, which regularizes affinity measures and overcomes inconsistent leaf assign-ments. The random-forest-based metric with PLS facilitates the establishment of consistent and point-wise correspondences. The proposed method has been applied to automatic phrase recognition using color and depth videos and point-wise correspondence. Extensive experiments demonstrate the effectiveness of the proposed method in affinity estimation in a comparison with the state-of-the-art.

Abstract Background The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. Methods A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. Results The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0–21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454–0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050–1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. Conclusions Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

Objectives: Machine learning is increasingly being used in the medical field. Based on machine learning models, the present study aims to improve the prediction performance of craniodentofacial morphological harmony judgment after orthodontic treatment and to determine the most significant factors.Methods: A dataset of 180 subjects was randomly selected from a large sample of 3,706 finished orthodontic cases from six top orthodontic treatment centers around China. Thirteen algorithms were used to predict the value of the cephalometric morphological harmony score of each subject and to search for the optimal model. Based on the feature importance ranking and by removing features, the regression models of machine learning (including the Adaboost, ExtraTree, XGBoost, and linear regression models) were used to predict and compare the score of harmony for each subject from the dataset with cross validations. By analyzing the prediction values, the most optimal model and the most significant cephalometric characteristics were determined.Results: When nine features were included, the performance of the XGBoost regression model was MAE = 0.267, RMSE = 0.341, and Pearson correlation coefficient = 0.683, which indicated that the XGBoost regression model exhibited the best fitting and predicting performance for craniodentofacial morphological harmony judgment. Nine cephalometric features including L1/NB (inclination of the lower central incisors), ANB (sagittal position between the maxilla and mandible), LL-EP (distance from the point of the prominence of the lower lip to the aesthetic plane), SN/OP (inclination of the occlusal plane), SNB (sagittal position of the mandible in relation to the cranial base), U1/SN (inclination of the upper incisors to the cranial base), L1-NB (protrusion of the lower central incisors), Ns-Prn-Pos (nasal protrusion), and U1/L1 (relationship between the protrusions of the upper and lower central incisors) were revealed to significantly influence the judgment.Conclusion: The application of the XGBoost regression model enhanced the predictive ability regarding the craniodentofacial morphological harmony evaluation by experts after orthodontic treatment. Teeth position, teeth alignment, jaw position, and soft tissue morphology would be the most significant factors influencing the judgment. The methodology also provided guidance for the application of machine learning models to resolve medical problems characterized by limited sample size.

Abstract Background Facial esthetics is a major concern of orthodontic patients. This study aims to evaluate orthodontic treatment-related thickness changes of the masseter muscles and surrounding soft tissues and the potential factors that would influence these changes during orthodontic treatment in female adults. Methods Forty-two female adult patients were included in this retrospective study and were divided into extraction (n = 22) and nonextraction (n = 20) groups. Pretreatment and posttreatment cone-beam computed tomography (CBCT) images were superimposed and reconstructed. The thickness changes of the masseter area of facial soft tissue (MAS), masseter muscles (MM) and surrounding fat tissue (FT) were measured. Pretreatment age, treatment duration, sagittal relationship (ANB), and vertical relationship (Frankfort-mandibular plane angle, FMA)-related MAS, MM and FT changes were compared between extraction and nonextraction groups. Spearman’s correlation coefficient was calculated between the above variables. Regression analysis was conducted to confirm the causal relations of the variables. Results The thickness of MAS and MM significantly decreased in both groups, with larger decreases (> 1 mm) in the extraction group. There were strong correlations (r > 0.7) between the thickness decrease in MAS and MM in both groups and moderate correlations (r > 0.4) between MAS and FT in the nonextraction group. A significantly greater decrease of MAS and MM were found to be moderately correlated with a smaller FMA (r > 0.4) in the extraction group. Scatter plots and regression analysis confirmed these correlations. Conclusions Masseter muscles and the surrounding soft tissue exhibited a significant decrease in thickness during orthodontic treatment in female adults. Low-angle patients experienced a greater decrease in soft tissue thickness in the masseter area in the extraction case. But the thickness changes were clinically very small in most patients.

Abstract Background With the aid of implants, Björk identified two-dimensional mandibular stable structures in cephalograms during facial growth. However, we do not know what the three-dimensional stable structures are with certainty. The purpose of this study was to identify the most stable mandibular landmarks in growing patients using three-dimensional images. Methods The sample was comprised of two cone-beam computed tomography (CBCT) scans taken about 4.6 years apart in 20 growing patients between the ages of 12.5 (T1) and 17.1 years (T2). After head orientation, landmarks were located on the chin (Pog), internal symphysis (Points C, D and E), and mandibular canals, which included the mental foramina (MF and MFA) and mandibular foramina (MdF). The linear distance change between Point C and these landmarks was measured on each CBCT to test stability through time. The reliability of the suggested stable landmarks was also evaluated. Results The total distance changes between Point C and points D, E, Pog, MF, and MFA were all less than 1.0 mm from T1 to T2. The reliability measures of these landmarks, which were measured by the Cronbach alpha, were above 0.94 in all three dimensions for each landmark. From T1 to T2, the distance changes from Point C to the right and left mandibular foramina were 3.39 ± 3.29 mm and 3.03 ± 2.83 mm, respectively. Conclusions During a growth period that averaged 4.6 years, ranging from 11.2 to 19.8 years old, the structures that appeared relatively stable and could be used in mandibular regional superimpositions included Pog, landmarks on the inferior part of the internal symphysis, and the mental foramen. The centers of the mandibular foramina and the starting points of the mandibular canal underwent significant changes in the transverse and sagittal dimensions.

Objectives: To compare the clinical characteristics and the dynamics of viral load between imported and non-imported patients with COVID-19. Design and methods: Data from 51 laboratory-confirmed patients were retrospectively analyzed. Results: The incubation period in the tertiary group was longer than that in the imported and secondary groups (both p < 0.05). Fever was the most common symptom at the onset of illness (73.33%, 58.82%, and 68.42%, respectively), and half of the patients had a low-grade temperature ( 0.05). For the tertiary group, the viral load was undetectable in half of the patients (52.63%) on day 7, and in all patients on day 14. For one third of the patients in the imported and secondary groups, the viral load remained positive on day 14 after the admission. Conclusions: COVID-19 can present as pneumonia with a low onset of symptoms, and the infectivity of SARS-CoV2 may gradually decrease in tertiary patients.

Abstract 5-Methylcytosine (5mC) is considered as a common epigenetic modification that plays an important role in the regulation of gene expression. At the same time, 5-hydroxymethylcytosine (5hmC) has been found as an emerging modification of cytosine bases of recent years. Unlike 5mC, global 5hmC levels vary from tissues that have differential distribution both in mammalian tissues and in the genome. DNA hydroxymethylation is the process that 5mC oxidates into 5hmC with the catalysis of TET (ten-eleven translocation) enzymes. It is an essential option of DNA demethylation, which modulates gene expression by adjusting the DNA methylation level. Various factors can regulate the demethylation of DNA, such as environmental toxins and mental stress. In this review, we summarize the progress in the formation of 5hmC, and obtaining 5hmC in a cell-free DNA sample presents multiple advantages and challenges for the subject. Furthermore, the clinical potential for 5hmC modification in dealing with cancer early diagnosis, prognostic evaluation, and prediction of therapeutic effect is also mentioned.

Abstract Background A functional appliance is commonly used to optimize the development of the facial skeleton in the treatment of Class II malocclusion. Recent three-dimensional(3D) image-based analysis offers numerous advantages in quantitative measurement and visualization in orthodontics. The aim of this study was to localize in 3D the skeletal effect produced by the Herbst appliance on the mandible using the geometric morphometric technique. Methods Twenty patients treated with a Herbst appliance and subsequent fixed appliances were included. Cone-beam computed tomography (CBCT) images were taken before treatment (T1), 8 weeks after Herbst appliance removal (T2), and after subsequent fixed appliance treatment (T3). Spatially dense morphometric techniques were used to establish the corresponding points of the mandible. The mandibular morphological changes from T1-T2, T2-T3, and T1-T3 were calculated for each patient by superimposing two mandibular models at two time points with robust Procrustes superimposition. These changes were then compared to the morphological changes estimated from normative mandibular growth curves over the same period. The proportion of cases exceeding the growth expression for controls was compared to a normal population using a one tailed binomial test. Results Approximately 1.5–2 mm greater condylar changes and 0.5 mm greater changes in the chin occurred from Tl to T2. This effect lasted until the completion of treatment (T1-T3), but there was no obvious skeletal effect during the orthodontic phase (T2-T3). Approximately 40–50% of the patient sample exceeded condylar growth by > 1.5 mm compared to untreated controls (p

Abstract Background The aim of this study was to establish a computer-aided automated method for cephalometric superimposition and to evaluate the accuracy of this method based on free-hand tracing. Methods Twenty-eight pairs of pre-treatment (T1) and post-treatment (T2) cephalograms were selected. Structural superimpositions of the anterior cranial base, maxilla and mandible were independently completed by three operators performing traditional hand tracing methods and by computerized automation using the feature matching algorithm. To quantitatively evaluate the differences between the two methods, the hand superimposed patterns were digitized. After automated and hand superimposition of T2 cephalograms to T1 cephalometric templates, landmark distances between paired automated and hand T2 cephalometric landmarks were measured. Differences in hand superimposition among the operators were also calculated. Results The T2 landmark differences in hand tracing between the operators ranged from 0.61 mm to 1.65 mm for the three types of superimposition. There were no significant differences in accuracy between hand and automated superimposition (p > 0.05). Conclusions Computer-aided cephalometric superimposition provides comparably accurate results to those of traditional hand tracing and will provide a powerful tool for academic research.

Abstract Background The limitation of current biomarker of early stage ovarian cancer and the anatomical location of ovarian (depths of the pelvic) make ovarian cancer difficult to be detected in early stage. Growing evidence shows exosomes as key information transmitters, it carried molecules, such as miRNAs, proteins, lipids, double-stranded DNA have been reported as promising biomarkers in many diseases. However, little is known about the protein and lipid composition of ovarian cancer. Methods Here, we report proteomic and lipidomic analysis of exosomes derived from ovarian cancer cells (SKOV-3) and ovarian surface epithelial cells (HOSEPiC). Results A total of 1433 proteins and 1227 lipid species were identified from two cell line derived exosomes. Several lipid species and proteins significantly differ in SKOV-3 derived exosomes compared to those from HOSEPiC. For example, we noted that ChE and ZyE species were in general more abundant in exosomes from SKOV-3 than from HOSEPiC; Collagen type V alpha 2 chain (COL5A2) and lipoprotein lipase (LPL) were significantly higher in SKOV-3 derived exosomes than HOSEpic (p

Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22’s only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2.

Periodontitis is a dysbiotic biofilm-induced and host-mediated inflammatory disease of tooth supporting tissues that leads to progressive destruction of periodontal ligament and alveolar bone, thereby resulting in gingival recession, deep periodontal pockets, tooth mobility and exfoliation, and aesthetically and functionally compromised dentition. Due to the improved biopharmaceutical and pharmacokinetic properties and targeted and controlled drug release, nano-based drug delivery systems have emerged as a promising strategy for the treatment of periodontal defects, allowing for increased efficacy and safety in controlling local inflammation, establishing a regenerative microenvironment, and regaining bone and attachments. This review provides an overview of nano-based drug delivery systems and illustrates their practical applications, future prospects, and limitations in the field of periodontal tissue regeneration.

Abstract Background Ovarian cancer during pregnancy is relatively rare and treatment strategies are inexperienced in surgery and chemotherapy. Multidisciplinary management of advanced epithelial ovarian cancer in pregnant patients with strong desire of fertility including sufficient mental and medical understanding, perioperative consideration, intraoperative decision, chemotherapy sensitivity and follow-up after treatment can gain successful outcomes for both maternal disease and fetus’s development. Case presentation A 34-year-old primigravidae was diagnosed with advanced epithelial ovarian tumor and then first cytoreductive surgery to resect macroscopical lesions and protect the uterus for fetus was performed following with four chemotherapy courses (docetaxel and carboplatin) before delivery and four other chemotherapy courses after delivery. Chemotherapy drugs were decided by sensitivity test and the patient’s anaphylaxis. Second surgery involved cesarean section with a healthy offspring and secondary cytoreductive surgery. Operative strategies were considered to gain a balance of disease and risk for fetus. Psychosocial support was provided during the course of diagnosis and treatment for a healthy coping situation. This patient relapsed 19 months after the last chemotherapy course and was treated by additional adjuvant therapy to a clinical remission. The 33-month baby boy has no evidence with disease until now. The follow-up of both mother and baby is still continuing. Conclusions Ovarian cancer during pregnancy has low incidence which must increase in future as women delay reproduction age. Ovarian cancer cytoreductive surgery and chemotherapy have limitation to handle conditions under a desire of fetus protection. Multidisciplinary treatment model is a therapeutic solution and a challenge for gynecological surgeons, medical oncologists, pathologists, obstetricians, neonatologists, pharmacists, anesthetist, and psychologists.

The molecular mechanisms underlying the development of thyroid cancer (TC) have been examined through extensive experiments. A large number of studies have shown that the incidences of thyroid cancer in women is much higher than that in men, so estrogen plays a key role in the development of thyroid cancer. Estrogen plays its growth-promoting role through classical genomic and non-genomic pathways mediated by membrane-bound estrogen receptors. It also can affect tumor progression by regulating the tumor microenvironment. We summarize the understanding of molecular mechanisms of estrogen signaling pathways in thyroid cancer. Furthermore, it will provide a new target for the treatment of thyroid carcinoma by blocking estrogen and its related action pathway.

Circular RNAs (circRNAs) are non-coding RNA molecules, and these are differentially expressed in various diseases, including cancer, suggesting that circRNAs can regulate certain diseases. CircRNAs can act as miRNAs sponges, RNA-binding protein (RBP) sponges, and translation regulators, and they can become an important part of the regulation of gene expression. Furthermore, because of their biomedical features in body fluids, such as high abundance, conservation, and stability, circRNAs are seen as potential biomarkers for various cancers. Cervical cancer (CC) is one of the main causes of cancer-related death in women, and there have been a large number of studies that analyze circRNAs as a new object to be evaluated in CC. Therefore, this review, by understanding the role of circRNAs in CC, may create innovative strategies in the future clinical diagnosis, treatment, and prognosis of CC and promote the development of personalized and highly accurate cancer therapy.

Cancer has been a daunting challenge for human beings because of its clonal heterogeneity and compositional complexity. Tumors are composed of cancer cells and a variety of non-cancer cells, which together with the extracellular matrix form the tumor microenvironment. These cancer-related cells and components and immune mechanisms can affect the development and progression of cancer and are associated with patient diagnosis, treatment and prognosis. As the first choice for the study of complex biological systems, single-cell transcriptional sequencing (scRNA-seq) has been widely used in cancer research. ScRNA-seq has made breakthrough discoveries in tumor heterogeneity, tumor evolution, metastasis and spread, development of chemoresistance, and the relationship between the tumor microenvironment and the immune system. These results will guide clinical cancer treatment and promote personalized and highly accurate cancer treatment. In this paper, we summarize the latest research progress of scRNA-seq and its guiding significance for clinical treatment.

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P

Recent discoveries have led to the development of novel ideas and techniques that have helped elucidate the correlation between epigenetics and tumor biology. Nowadays, the field of tumor genetics has evolved to include a new type of regulation by epigenetics. An increasing number of studies have demonstrated the importance of DNA methylation and hydroxymethylation in specific genes in the progression of cervical cancer. Determining the methylation and hydroxymethylation profiles of these genes will help in the early prevention and diagnosis, monitoring recurrence, prognosis, and treatment of patients with cervical cancer. In this review, we focus on the significance of aberrant DNA methylation and hydroxymethylation in cervical cancer and the use of these epigenetic signatures in clinical settings.

Abstract Background Orthodontic treatment can result in root resorption (RR). Traditional two-dimensional (2D) data exhibit magnification, deformation and positioning problems. Cone beam computed tomography (CBCT) contains more accurate three-dimensional (3D) information. This study identified and qualified the extent and location of root resorption using cone beam computed tomography (CBCT) after comprehensive orthodontic treatment. Methods Studies comparing the RR before and after comprehensive orthodontic treatment using CBCT were identified using electronic searches of databases, including Cochrane, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Web of Science, and manual searches in relevant journals and the reference lists of the included studies until Oct 25, 2017. The extraction of data and the risk of bias evaluation were conducted by two investigators independently. The methodological quality of the included studies was assessed using the methodological index for non-randomized studies (MINORS). Studies that reported the length and volume of teeth were used for quantitative analyses. Results Twelve studies were included in the meta-analysis. The length of all teeth after intervention was significantly shorter than that before treatment (MD = 0.80, 95% CI 0.56, 1.03, P

Abstract Exosomes are nanoparticles(40-100 nm) secreted by most cells in the body, which can be isolated from several types of extracellular fluids. It has been shown that exosomes play a key role in intercellular communication and in transportation of genetic information. Emerging evidence shows that exosomes are mediators of metastasis in tumour cells, stromal cells and the extracellular matrix component through the shuttling of cargo, such as proteins, lipids, RNAs, double-stranded DNAs, non-transcribed RNAs, and microRNAs. This phenomenon has been indicated in both tumourigenesis and drug resistance. In this review, we introduce new methods of exosome extraction, focusing on the emerging role of exosomes in ovarian cancer, and discuss their potential clinical applications.

Ovarian cancer is the most lethal gynecological malignancy worldwide. Most patients are diagnosed at late stages because of atypical symptoms and the lack of effective early diagnostic measures. The mechanisms underlying the oncogenesis and development of ovarian cancer are not clear. Macrophages, immune cells derived from the innate immune system, have two states of polarization (M1 and M2) that develop in response to different stimuli. The polarization and differentiation of macrophages into the cancer-inhibiting M1 and cancer-promoting M2 types represent the two states of macrophages in the tumor microenvironment. The interaction of polarized macrophages with cancer cells plays a crucial role in a variety of cancers. However, the effects of macrophage M1/M2 polarization on ovarian cancer have not yet been systematically and fully discussed. In this review, we discuss not only the occurrence, development and influences of macrophage polarization but also the association between macrophage polarization and ovarian cancer. The polarization of macrophages into the M1 and M2 phenotypes plays a pivotal role in ovarian cancer initiation, progression, and metastasis, and provides targets for macrophage-centered treatment in the cancer microenvironment for ovarian cancer therapy. We also addressed the regulation of macrophage polarization in ovarian cancer via noncoding RNAs, exosomes, and epigenetics.

Fragile X syndrome (FXS) is the most common congenital hereditary disease of low intelligence after Down syndrome. Its main pathogenic gene is fragile X mental retardation 1 (FMR1) gene associated with intellectual disability, autism, and fragile X-related primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS). FMR1 gene transcription leads to the absence of fragile X mental retardation protein (FMRP). How to relieve or cure disorders associated with FXS has also become a clinically disturbing problem. Previous studies have recently shown that long noncoding RNAs (lncRNAs) contribute to the pathogenesis. And it has been identified that several lncRNAs including FMR4, FMR5, and FMR6 contribute to developing FXPOI/FXTAS, originating from the FMR1 gene locus. FMR4 is a product of RNA polymerase II and can regulate the expression of relevant genes during differentiation of human neural precursor cells. FMR5 is a sense-oriented transcript while FMR6 is an antisense lncRNA produced by the 3′ UTR of FMR1. FMR6 is likely to contribute to developing FXPOI, and it overlaps exons 15–17 of FMR1 as well as two microRNA binding sites. Additionally, BC1 can bind FMRP to form an inhibitory complex and lncRNA TUG1 also can control axonal development by directly interacting with FMRP through modulating SnoN–Ccd1 pathway. Therefore, these lncRNAs provide pharmaceutical targets and novel biomarkers. This review will: (1) describe the clinical manifestations and traditional pathogenesis of FXS and FXTAS/FXPOI; (2) summarize what is known about the role of lncRNAs in the pathogenesis of FXS and FXTAS/FXPOI; and (3) provide an outlook of potential effects and future directions of lncRNAs in FXS and FXTAS/FXPOI researches.

Objectives. Cervical clear cell adenocarcinoma (CCAC) is a rare malignant tumor with independent biological behavior in the female reproductive system. In this report, we collect the clinical and histopathological characteristics of 18 CCAC patients without exposure to diethylstilbestrol (DES) and conduct relevant clinical analysis. Methods. We retrospectively analyzed the clinical data of 18 patients with CCAC who were diagnosed and treated from January 2009 to August 2017 in the Second Hospital of Jilin University. Results. A total of 18 patients were enrolled. The age of patients ranged from 37 to 74 years with the peak incidence between 45 and 55 years. The median age was 53 years. The most common symptom was vaginal bleeding (66.7%, 12/18). The most common type of lesion was the endocervical type (66.7%, 12/18). The negative rate of human papillomavirus (HPV) examination was 88.9% (8/9). Based on the staging criteria of the International Federation of Gynecology and Obstetrics (FIGO) cervical cancer clinical stage in 2018, 55.6% patients were stage I (n=10), 16.7% were stage II (n=3), 22.2% were stage III (n=4), and 5.6% were stage IV (n=1). Seventeen patients underwent surgery; 64.7% (11/17) of cases showed infiltration of the entire layer of the cervix, pelvic lymph node (PLN) metastasis was observed in 4 patients (26.7%, 4/15), endometrium metastasis was observed in 4 patients (25%, 4/16), and 13 patients (72.2%, 13/18) were diagnosed at an early stage (stage IB1-IIA2). Fifteen patients’ immunohistochemistry indicated that napsin A, CK7, CK (AE1/AE3), and PAX-8 were positive, and p53, p16, ER, and vimentin were expressed to different degrees. Follow-up data were obtained in 13 patients (72.2%, 13/18). One patient died of recurrence 5 months after surgery, and the other patients’ progression-free survival (PFS) ranged from 9 to 59 months. Tumor size (>4 cm), tumor stage (FIGO IIA2-IV), PLN, and endometrium metastasis had negative effects on PFS (P

Perineal groove is a rare anoperineal congenital malformation disease that usually affects newborn females. It is unknown to many clinicians, which usually leads to misdiagnosis. The pathogenesis of perineal groove is not clear, and there are few cases reported in the current medical literature. Perineal grooves in two newborn babies were described in this report, and the literature on perineal groove was also reviewed and analyzed to improve the recognition of this disease.

Endometriosis, defined as the presence of ectopic endometrial glands and stroma outside the uterine cavity, is a chronic, hormone-dependent gynecologic disease affecting millions of women across the world, with symptoms including chronic pelvic pain, dysmenorrhea, dyspareunia, dysuria, and subfertility. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation, with the involvement of various mechanisms of development. More and more evidence reveals an important contribution of epigenetic modification not only in endometriosis but also in mechanisms of endometriosis malignant transformation, including DNA methylation and demethylation, histone modifications, and miRNA aberrant expressions. In this present review, we mainly summarize the research progress about the current knowledge regarding the epigenetic modifications of the relations between endometriosis malignant transformation and ovarian cancer in an effort to identify some risk factors probably associated with ectopic endometrium transformation.

Cervical cancer is one of the most common gynecological tumors in females, which is closely related to high-rate HPV infection. Methylation alteration is a type of epigenetic decoration that regulates the expression of genes without changing the DNA sequence, and it is essential for the progression of cervical cancer in pathogenesis while reflecting the prognosis and therapeutic sensitivity in clinical practice. Hydroxymethylation has been discovered in recent years, thus making 5-hmC, the more stable marker, attract more attention in the field of methylation research. As markers of methylation, 5-hmC and 5-mC together with 5-foC and 5-caC draw the outline of the reversible cycle, and 6-mA takes part in the methylation of RNA, especially mRNA. Furthermore, methylation modification participates in ncRNA regulation and histone decoration. In this review, we focus on recent advances in the understanding of methylation regulation in the process of cervical cancer, as well as HPV and CIN, to identify the significant impact on the prospect of overcoming cervical cancer.

Mesenchymal stem cells have been at the forefront of regenerative medicine for many years. Exosomes, which are nanovesicles involved in intercellular communication and the transportation of genetic material transportation that can be released by mesenchymal stem cells, have been recently reported to play a role in cell-free therapy of many diseases, including myocardial infarction, drug addiction, and status epilepticus. They are also thought to help ameliorate inflammation-induced preterm brain injury, liver injury, and various types of cancer. This review highlights recent advances in the exploration of mesenchymal stem cell-derived exosomes in therapeutic applications. The natural contents, drug delivery potency, modification methods, and drug loading methods of exosomes are also discussed.

ObjectiveWhether the orthodontic treatment with premolar extraction and maximum anchorage in adults will lead to a narrowed upper airway remains under debated. The study aims to investigate the airway changes after orthodontic extraction treatment in adult patients with Class II and hyperdivergent skeletal malocclusion.Materials and methodsThis retrospective study enrolled 18 adults with Class II and hyperdivergent skeletal malocclusion (5 males and 13 females, 24.1 ± 3.8 years of age, BMI 20.33 ± 1.77 kg/m2). And 18 untreated controls were matched 1:1 with the treated patients for age, sex, BMI, and skeletal pattern. CBCT images before and after treatment were obtained. DOLPHIN 11.7 software was used to reconstruct and measure the airway size, hyoid position, and craniofacial structures. Changes in the airway and craniofacial parameters from pre to post treatment were assessed by Wilcoxon signed rank test. Mann-Whitney U test was used in comparisons of the airway parameters between the treated patients and the untreated controls. Significant level was set at 0.05.ResultsThe upper and lower incisors retracted 7.87 mm and 6.10 mm based on the measurement of U1-VRL and L1-VRL (P < 0.01), while the positions of the upper and lower molars (U6-VRL, and L6-VRL) remained stable. Volume, height, and cross-sectional area of the airway were not significantly changed after treatment, while the sagittal dimensions of SPP-SPPW, U-MPW, PAS, and V-LPW were significantly decreased (P < 0.05), and the morphology of the cross sections passing through SPP-SPPW, U-MPW, PAS, and V-LPW became anteroposteriorly compressed (P ConclusionsThe airway changes after orthodontic treatment with premolar extraction and maximum anchorage in adults are mainly morphological changes with anteroposterior dimension compressed in airway cross sections, rather than a decrease in size.

The purpose of this cross-sectional research was to explore the relationship of the mandibular dental and basal bone archforms between severe Skeletal Class II (SC2) and Skeletal Class III (SC3) malocclusions. We also compared intercanine and intermolar widths in these two malocclusion types. Thirty-three virtual pretreatment mandibular models (Skeletal Class III group) and Thirty-five Skeletal Class II group pretreatment models were created with a laser scanning system. FA (the midpoint of the facial axis of the clinical crown)and WALA points (the most prominent point on the soft-tissue ridge)were employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2). In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.