Geometric Understanding of Discriminability and Transferability for Visual Domain Adaptation.

To overcome the restriction of identical distribution assumption, invariant representation learning for unsupervised domain adaptation (UDA) has made significant advances in computer vision and pattern recognition communities. In UDA scenario, the training and test data belong to different domains while the task model is learned to be invariant. Recently, empirical connections between transferability and discriminability have received increasing attention, which is the key to understand the invariant representations. However, theoretical study of these abilities and in-depth analysis of the learned feature structures are unexplored yet. In this work, we systematically analyze the essentials of transferability and discriminability from the geometric perspective. Our theoretical results provide insights into understanding the co-regularization relation and prove the possibility of learning these abilities. From methodology aspect, the abilities are formulated as geometric properties between domain/cluster subspaces (i.e., orthogonality and equivalence) and characterized as the relation between the norms/ranks of multiple matrices. Two optimization-friendly learning principles are derived, which also ensure some intuitive explanations. Moreover, a feasible range for the co-regularization parameters is deduced to balance the learning of geometric structures. Based on the theoretical results, a geometry-oriented model is proposed for enhancing the transferability and discriminability via nuclear norm optimization. Extensive experiment results validate the effectiveness of the proposed model in empirical applications, and verify that the geometric abilities can be sufficiently learned in the derived feasible range.

Intraocular schwannoma: case series of 28 patients and literature review.

PURPOSE: Intraocular schwannoma is a rare tumour, which is often misdiagnosed. We presented the demographics and clinical characteristics of patients with intraocular schwannoma. METHODS: Retrospective case series were collected between May 2005 and July 2021 in Beijing Tongren Hospital. RESULTS: A total of 28 patients were diagnosed with intraocular schwannoma on histopathological examination of surgical specimen. The median age was 39 years (range: 12-64). Fourteen patients were female and 14 were male. Among the all subjects, 21/28 patients (75.0%) presented as visual loss, and 3/28 patients (10.7%) had visual field loss. Intraocular schwannoma presented as nonpigmented mass in the ciliary body in 12/28 cases (42.9%), in the choroid in 9/28 cases (32.1%), and in ciliochoroid in 7/28 cases (25.0%). Intraocular schwannoma was often clinically misdiagnosed as uveal melanoma, which occurred in 16/28 patients (57.1%). Tumour excision with pars plana vitrectomy was performed for all included patients. Endoresection with lens removal was performed for tumours in the choroid, while transscleral resection was performed for tumours located in ciliary body or ciliochoroid. Increased light transmission was detected in 12/28 cases (42.9%). In the consecutive follow-up (median: 73 months, range: 7-193 months), no cases of recurrence or metastatic disease were detected. CONCLUSIONS: Intraocular schwannoma is a rare benign tumour. It usually presents as nonpigmented mass, which can easily be misdiagnosed as nonpigmented uveal melanoma.

Hepatitis B Virus Surface Antigen Promotes Stemness of Hepatocellular Carcinoma through Regulating MicroRNA-203a.

Background and Aims: Patients with persistent positive hepatitis B surface antigen (HBsAg), even with a low HBV-DNA load, have a higher risk of hepatocellular carcinoma (HCC) than those without HBV infection. Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms, this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA, and to explore underlying mechanisms. Methods: We screened out miR-203a, the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study. In vitro and in vivo functional experiments were performed to assess its regulatory function. The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study. Results: MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis. The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells. We demonstrated the function of miR-203a in inhibiting HCC cell proliferation, migration, clonogenic capacity, and tumor development in vivo. Furthermore, the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers. In concordance with our study, the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a. We also found that BMI1, a gene maintains the self-renewal capacity of stem cells, showed a significant negative correlation with miR-203a in HCC specimen (p<0.001). Similarly, opposite BMI1 changes after overexpression/knockdown of miR-203a were also confirmed in vitro. Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding. Conclusions: HBsAg may promote the development of HCC and tumor stemness by inhibiting miR-203a, resulting in poor prognosis. miR-203a may serve as a crucial treatment target in HBsAg-positive HCC. More explicit mechanistic studies and animal experiments need to be conducted as a next step.

Rare giant corneal keloid presenting 26 years after trauma: A case report.

BACKGROUND: Corneal keloid is a rare clinical disease with an unknown etiology, which is easily misdiagnosed. Surgery is the most effective treatment but is rarely reported in the literature. Herein, we report the clinical features, histopathology, and surgical outcome of a giant corneal keloid with trophoblastic vessels and discuss the genesis of the mass. CASE SUMMARY: A 36-year-old young man was admitted to the hospital because of a large mass on the surface of the left cornea. The patient had suffered an injury to his left eye at the age of 6-years-old; however, as the injury did not cause cornea perforation, he did not undergo treatment. Slit lamp exam showed a large, elevated, opaque lesion that covered the entire cornea and protruded from the surface of the eyeball. Anterior segment optical coherence tomography (AS-OCT) revealed a lesion of irregular density involving the anterior stroma. We suspected a secondary corneal fibroproliferative mass based on the clinical history, and slit lamp and AS-OCT findings. The patient subsequently underwent a superficial keratectomy and keratoplasty, and the final diagnosis of corneal keloid was confirmed by intraoperative histopathological examination. CONCLUSION: Non-penetrating corneal trauma damages corneal epithelium basement membrane, initiating stromal fibrosis and causing corneal keloids. AS-OCT and biopsy confirm diagnosis.

Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma.

LAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role in the inhibition of T cells. However, the FGL1 expression in circulating tumor cells (CTCs) and its clinical significance in hepatocellular carcinoma (HCC) remain unclear. Therefore, this bioinformatics analysis was performed to assess the expression of FGL1 in various tumors and its association with immune infiltration. After that, CTCs from 109 HCC patients were detected and the immunofluorescence staining was performed (CD45, EpCAM, CK8/18/19, Vimentin, Twist, DAPI and FGL1). Then, we investigated FGL1 expression and EMT of CTCs and analyzed its relationship with patient survival and clinical relevance. Bioinformatic results showed that FGL1 expression was abnormal in various tumor and it was correlated with the infiltration level of several immune cells. FGL1 expression was detected in CTCs of 40 patients (36.7%). The proportion of advanced TNM stage (P<0.001) and distant metastasis(P=0.020) in FGL1 positive patients was higher than that of FGL1 negative patients. In addition, patients with FGL1 positive circulating tumor cells had worse postoperative survival than FGL1 negative patients (p=0.0297). The mixed phenotypic CTC presented a higher level of FGL1 expression than any other types, the number of which also predicted worse prognosis(p=0.0443). We also found that the expression of FGL1 on CTCs was associated with the level of FGL1 in tumor tissues. Of 12 patients receiving PD-1/PD-L1 blockade in a total of 109 cases, 8 out of 10 patients with FGL1 positive CTC showed immunotherapy resistance. It is the first study that suggested FGL1 expression in CTCs as an indicator of the poor prognosis in HCC patients. CTC detection may serve as a promising replacement for determination of tumor tissue FGL1 expression and provide evidence for the application of immunotherapy.

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR-21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia.

Innervation and extracellular vesicle secretion co-exist in the local tissue microenvironment for message transfer, but whether they are interconnected to regulate organ homeostasis remains unknown. Sympatho-adrenergic activation is implicated in stress-induced depression and leads to bone loss, but the mechanisms and therapeutics are incompletely elucidated. Here, it is revealed that sympathetic neurostress through the ß1/2 -adrenergic receptor (ß1/2-AR) signaling triggers the transcription response of a microRNA, miR-21, in osteoblasts, which is transferred to osteoclast progenitors via exosomes for dictating osteoclastogenesis. After confirming that miR-21 deficiency retards the ß1/2-AR agonist isoproterenol (ISO)-induced osteopenia, it is shown that the pharmacological inhibition of exosome release by two clinically-relevant drugs, dimethyl amiloride and omeprazole, suppresses osteoblastic miR-21 transfer and ameliorates bone loss under both ISO and chronic variable stress (CVS)-induced depression conditions. A targeted delivery approach to specifically silence osteoblastic miR-21 is further applied, which is effective in rescuing the bone remodeling balance and ameliorating ISO- and CVS-induced osteopenias. These results decipher a previously unrecognized paradigm that neural cues drive exosomal microRNA communication to regulate organ homeostasis and help to establish feasible strategies to counteract bone loss under psychological stresses.

Helicobacter pylori-induced REDD1 modulates Th17 cell responses that contribute to gastritis.

OBJECTIVE: Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, which is induced in response to multiple stimuli. However, the regulation, function and clinical relevance of REDD1 in Helicobacter pylori-associated gastritis are presently unknown. APPROACH: Immunohistochemistry, real-time PCR and Western blot analyses were performed to examine the levels of REDD1 in gastric samples from H. pylori-infected patients and mice. Gastric tissues from Redd1-/- and wildtype (WT, control) mice were examined for inflammation. Gastric epithelial cells (GECs), monocytes and T cells were isolated, stimulated and/or cultured for REDD1 regulation and functional assays. RESULTS: REDD1 was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cytotoxin associated gene A (cagA) that activated MAPKp38 pathway to mediate NF-κB directly binding to REDD1 promoter. Human gastric REDD1 increased with the severity of gastritis, and mouse REDD1 from non-marrow chimera-derived cells promoted gastric inflammation that was characterized by the influx of MHCII+ monocytes. Importantly, gastric inflammation, MHCII+ monocyte infiltration, IL-23 and IL-17A were attenuated in Redd1-/- mice. Mechanistically, REDD1 in GECs regulated CXCL1 production, which attracted MHCII+ monocytes migration by CXCL1-CXCR2 axis. Then H. pylori induced MHCII+ monocytes to secrete IL-23, which favored IL-17A-producing CD4+ cell (Th17 cell) polarization, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: The present study identifies a novel regulatory network involving REDD1, which collectively exert a pro-inflammatory effect within gastric microenvironment. Efforts to inhibit this REDD1-dependent pathway may prove valuable strategies in treating of H. pylori-associated gastritis.

The RB1 Mutation Spectrum and Genetic Management Consultation in Pediatric Patients with Retinoblastoma in Beijing, China.

OBJECTIVE: The present study screened the structural mutations of the retinoblastoma (RB1) gene using gene capture and a preliminary exploration of the correlation between the genotypes and phenotypes. METHODS: A total of 45 formalin-fixed paraffin-embedded (FFPE) tissue samples and 12 peripheral venous blood samples from patients with retinoblastoma (RB) confirmed by pathological examination at Beijing Tongren Hospital were collected between May 2019 and May 2021. DNA from the samples was extracted, sequenced, and analyzed to detect the mutations in the RB1 gene by designing the targeted capture probes for exons and the flanking sequences of the gene. RESULTS: Of the 45 FFPE tissue samples, 23 were from male patients and 22 were from female patients, all aged between 4 months and 10 years, with an average age of 2.5 ± 1.3 years. Two of these patients had bilateral RB and 43 had unilateral RB (23 in the right eye and 20 in the left eye). Of the 12 peripheral venous blood samples, 7 were from male patients and 5 were from female patients, all aged between 8 months and 4 years, with an average age of 1.3 ± 0.9 years. Two of these patients had bilateral RB and 10 had unilateral RB (8 in the right eye and 2 in the left eye). Three de novo pathogenic mutations were found in the FFPE tissues, along with one de novo potentially pathogenic mutation, while three de novo potentially pathogenic mutations were found in the blood samples. CONCLUSION: Gene capture is a low-cost and efficient method for the gene sequencing of RB. A total of seven de novo mutations were identified through mutation testing of the pathogenic gene RB1 in 56 pediatric patients with RB. This complemented the mutation spectrum of the RB1 gene and helped to improve the molecular diagnosis of RB, thereby providing a basis for genetic counseling and prediction of the clinical phenotype, as well as for the genetic testing of the offspring of patients with RB. CLINICAL REGISTRATION NUMBER: ChiCTR-EPC-17013892.

Clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma and intracranial segment of Retrobulbar optic nerve invasion.

BACKGROUND: To analyze the clinical characteristics, treatment and prognosis of children with unilateral retinoblastoma (RB) and intracranial segment of retrobulbar optic nerve invasion. METHODS: A total of 14 children with unilateral RB and intracranial segment of retrobulbar optic nerve invasion were enrolled in this retrospective study from January 2009 to December 2018. Clinical characteristics, treatment and prognosis were collected and analyzed. Survival curves were calculated by Kaplan-Meier method. RESULTS: Of 14 cases, there were 7 male and 7 female, ranging in age from 22.85 to 121.97 months (median, 41.03 months). Seventy-one percent of patients came from first-tier cities in China and effected in the left eye. Magnetic resonance imaging (MRI) results indicated that all patients presented with thickened and enhanced optic nerve and intracranial segment of optic nerve invasion. Nine patients received comprehensive therapeutic regimen (chemotherapy, eye enucleation, radiotherapy and intrathecal therapy). The patients were followed up to December 2019, with a median follow-up of 20.6 months. The median disease specific survival was 48.99 ± 8.62 months, and the overall survival (OS) rate was 64.3%. Radiotherapy and comprehensive therapeutic regimen had significant impact on survival time (all p < 0.05). CONCLUSIONS: The overall prognosis of unilateral RB patients with intracranial segment of retrobulbar optic nerve invasion was poor. Chemotherapy and surgical treatment were necessary, but more attention should be paid to radiotherapy and intrathecal therapy for improving prognosis.

Gli1+ Cells Couple with Type H Vessels and Are Required for Type H Vessel Formation.

Mesenchymal stem/stromal cells (MSCs) reside in the perivascular niche and modulate tissue/organ homeostasis; however, little is known about whether and how their localization and function are linked. Particularly, whether specific MSC subsets couple with and regulate specialized vessel subtypes is unclear. Here, we show that Gli1+ cells, which are a subpopulation of MSCs couple with and regulate a specialized form of vasculature. The specific capillaries, i.e., CD31hiEMCNhi type H vessels, are the preferable vascular subtype which Gli1+ cells are adjacent to in bone. Gli1+ cells are further identified to be phenotypically coupled with type H endothelium during bone growth and defect healing. Importantly, Gli1+ cell ablation inhibits type H vessel formation associated with suppressed bone generation and regeneration. Mechanistically, Gli1+ cells initiate angiogenesis through Gli and HIF-1α signaling. These findings suggest a morphological and functional framework of Gli1+ cells modulating coupled type H vasculature for tissue homeostasis and regenerative repair.

Targeting ferroptosis contributes to ATPR-induced AML differentiation via ROS-autophagy-lysosomal pathway.

Ferroptosis, a newly discovered form of non-apoptotic cell death, is induced by an excessive degree of iron-dependent lipid peroxide. ATPR, a novel all-trans retinoic acid (ATRA) derivative, has been extensively developed to show superior anticancer effect than ATRA in acute myeloid leukemia (AML). However, whether ferroptosis exists during ATPR treatment of AML remains unclear. Herein, we found that ferroptosis occurred in an AML xenograft mouse model of ATPR treatment. In vitro, ATPR was verified to induce ferroptosis in a dose-dependent manner by proferroptotic protein marker, lipid peroxidation, and lipid ROS, which could be significantly reversed by ferrostatin-1. Using lysosomal inhibitor chloroquine and iron chelator desferrioxamine, we further revealed that ATPR-induced ferroptosis was regulated by autophagy via iron homeostasis, especially Nrf2. Furthermore, targeting ferroptosis contributes to ATPR-induced AML differentiation. In conclusion, these results indicated that ferroptosis play an important role in ATPR-induced differentiation, and suggested that ATPR would provide a potential therapeutic value for AML treatment.

HS-SPME GC-MS characterization of volatiles in processed walnuts and their oxidative stability.

Processed walnuts including hot air-dried and roasted walnuts were prepared. Volatiles in raw and processed walnuts were analyzed using head-space solid phase microextraction combined with gas chromatography and mass spectrometry. Oxidative stability of hot air-dried walnuts in different antioxidants, with or without vacuum package was studied to find a proper package for oxidation stability of hot air-dried walnuts. The results showed that there were 14 volatiles in raw walnuts, 28 in hot air-dried walnuts and 38 in roasted walnuts. The changes of oil quality indices, total phenols, malondialdehyde and free radical scavenging activities during storage at 60 °C showed that the oil oxidation increased with storage time. The addition of antioxidants and vacuum package could slow down the oxidation. Vacuum aluminum foil package (14 × 20 cm) can delay the oil oxidation and extend the shelf life to ~ 230 days of hot air-dried walnuts at 20 °C. With added antioxidant this was extended to ~ 257 days.

Psychometric properties of the Chinese version of the modified polycystic ovary syndrome health-related quality-of-life questionnaire.

BACKGROUND: The modified polycystic ovary syndrome health-related quality-of-life questionnaire (MPCOSQ) is a 30-item instrument measuring quality-of-life in English-speaking patients with polycystic ovary syndrome (PCOS). We aimed to: 1) cross-culturally adapt the MPCOSQ into Chinese, and 2) assess the validity and reliability of the Chinese version of the MPCOSQ (Chi-MPCOSQ). METHODS: The MPCOSQ was translated using the forward-backward method, and its validity and reliability were assessed among 283 Chinese patients with PCOS. Internal consistency reliability and test-retest reliability were assessed by Cronbach's α and intra-correlation coefficient (ICC), respectively. Construct validity was tested through exploratory factor analysis and confirmatory factor analysis. Discriminant validity was assessed by Mann-Whitney U test to compare the scores on the Chi-MPCOSQ between 283 women with PCOS and 93 women without PCOS. RESULTS: Exploratory factor analysis generated a 7-factor structure of the 30-item version of the Chi-MPCOSQ, which accounted for 77% of the overall variance. The Chi-MPCOSQ had high internal consistency (Cronbach's α = 0.88) and good test-retest reliability (ICC = 0.89). Compared to PCOS patients, women without PCOS had consistently lower scores for every dimension of the Chi-MPCOSQ, demonstrating its good discriminant validity. CONCLUSION: The Chi-MPCOSQ is a valid and reliable instrument for measuring quality-of-life among Chinese women with PCOS.

ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARα/LDHB/ERK-glycolysis signalling axis.

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB-targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK-glycolysis signalling axis. Further studies should focus on the underlying leukaemia-promoting mechanisms and investigate LDHB as a therapeutic target.

Generalized Conditional Domain Adaptation: A Causal Perspective With Low-Rank Translators.

Learning domain adaptive features aims to enhance the classification performance of the target domain by exploring the discriminant information from an auxiliary source set. Let X denote the feature and Y as the label. The most typical problem to be addressed is that P XY has a so large variation between different domains that classification in the target domain is difficult. In this paper, we study the generalized conditional domain adaptation (DA) problem, in which both P Y and P X|Y change across domains, in a causal perspective. We propose transforming the class conditional probability matching to the marginal probability matching problem, under a proper assumption. We build an intermediate domain by employing a regression model. In order to enforce the most relevant data to reconstruct the intermediate representations, a low-rank constraint is placed on the regression model for regularization. The low-rank constraint underlines a global algebraic structure between different domains, and stresses the group compactness in representing the samples. The new model is considered under the discriminant subspace framework, which is favorable in simultaneously extracting the classification information from the source domain and adaptation information across domains. The model can be solved by an alternative optimization manner of quadratic programming and the alternative Lagrange multiplier method. To the best of our knowledge, this paper is the first to exploit low-rank representation, from the source domain to the intermediate domain, to learn the domain adaptive features. Comprehensive experimental results validate that the proposed method provides better classification accuracies with DA, compared with well-established baselines.

Discriminative Residual Analysis for Image Set Classification with Posture and Age Variations.

Image set recognition has been widely applied in many practical problems like real-time video retrieval and image caption tasks. Due to its superior performance, it has grown into a significant topic in recent years. However, images with complicated variations, e.g., postures and human ages, are difficult to address, as these variations are continuous and gradual with respect to image appearance. Consequently, the crucial point of image set recognition is to mine the intrinsic connection or structural information from the image batches with variations. In this work, a Discriminant Residual Analysis (DRA) method is proposed to improve the classification performance by discovering discriminant features in related and unrelated groups. Specifically, DRA attempts to obtain a powerful projection which casts the residual representations into a discriminant subspace. Such a projection subspace is expected to magnify the useful information of the input space as much as possible, then the relation between the training set and the test set described by the given metric or distance will be more precise in the discriminant subspace. We also propose a nonfeasance strategy by defining another approach to construct the unrelated groups, which help to reduce furthermore the cost of sampling errors. Two regularization approaches are used to deal with the probable small sample size problem. Extensive experiments are conducted on benchmark databases, and the results show superiority and efficiency of the new methods.

[The symmetry of nasal maxillary complex of patients with unilateral complete cleft lip and palate at the stage of mixed dentition-A cone beam CT study].

PURPOSE: To investigate the symmetry of nasal maxillary complex in the three-dimensional directions of patients with unilateral complete cleft lip and palate(UCLP) at the stage of mixed dentition. METHODS: Craniofacial cone-beam CT(CBCT) images of 20 UCLP patients at the stage of mixed dentition were selected. Three-dimensional reconstruction of bone tissue was carried out by Mimics software, nasal root point and 32 markers with the same name of the healthy side and the cleft side of the nasal maxillary complex were traced, three-dimensional reference planes were set up, then the distances between the points to the three-dimensional planes were measured respectively. SPSS 22.0 software package was used to analyze the data. RESULTS: In the horizontal direction, compared with the non-cleft side, the width of the cleft side of the maxilla at INM and SPC was smaller, the width of maxilla at LPA and SPr was larger, the differences were statistically significant (P<0.05). In the sagittal direction, compared with the non-cleft side, the depth of LPA, Maz and SPr at the cleft side was larger, the depth of SPM and SPC was smaller, the differences were statistically significant (P<0.05).In the vertical direction, the positions of LPA, INM and Maz at the cleft side was lower than the non-cleft side, SPC and SPr were higher, the differences were statistically significant(P<0.05). The remaining points had no significant difference (P>0.05). CONCLUSIONS: The nasal maxillary complex of UCLP patients at the stage of mixed dentition is asymmetric in three directions. The asymmetric locations were mainly located in the nasal cavity and alveolar bone. No obvious asymmetry is found in the orbital region and the maxillary region far from the cleft.

[Association between cervical vertebral maturation stages and dental calcification stages in patients with unilateral complete cleft lip and palate].

OBJECTIVE: The purpose of the study is to investigate the relationship between dental calcification stages (DCS) and cervical vertebral maturation stages (CVMS) in patients with unilateral complete cleft lips and palates (UCLP) and to provide a theoretical basis for the treatment time selection of cleft lip and palate (CLP) patients. METHODS: A total of 123 UCLP patients and 215 non-CLP subjects were selected. The DCS of the left mandibular canine, premolar, and second molar in non-CLP subjects and on both cleft sides of UCLP patients were assessed utilizing the Demirjian method. CVMS was observed utilizing the Baccetti method. The results were analyzed by Spearman rank correlation, and the correlation coefficients were compared. RESULTS: There was a correlation between the CVMS and the DCS of the left mandibular canine, the first premolar, the second premolar, and the second molar in the non-CLP subjects and on both cleft sides of the UCLP patients (r=0.762-0.864, P<0.05; r=0.809-0.914, P<0.05, respectively). The correlation between the CVMS and the DCS of the mandibular first premolar was highest among the UCLP patients. Except for the first and the second premolars of UCLP females, the correlation between the DCS and the CVMS of the other teeth did not differ among the non-CLP subjects (P>0.05). CONCLUSIONS: DCS can be utilized as a biological index to determine the growth development statuses. The correlation between the CVMS and the DCS of the mandibular first premolar was the highest.

Effective targeted therapy for drug-resistant infection by ICAM-1 antibody-conjugated TPGS modified ß-Ga2O3:Cr3+ nanoparticles.

The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared ß-Ga2O3:Cr3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga2O3) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods: I-TPGS/Ga2O3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga2O3/TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga2O3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga2O3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga2O3/TIG were finally evaluated using acute pneumonia mice. Results: It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga2O3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo. Additionally, targeted delivery of I-TPGS/Ga2O3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion: It is of great value to apply I-TPGS/Ga2O3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.

Acidic pH-Activated Gas-Generating Nanoparticles with Pullulan Decorating for Hepatoma-Targeted Ultrasound Imaging.

Contrast-enhanced ultrasound (US) is a widely used imaging modality for hepatocellular carcinoma diagnosis. Mostly, US imaging is confined to the intravascular process because of the limitation of the microbubble contrast agent currently utilized. Targeted contrast agents that incline to accumulate in tumor tissue or tumor cells and enhance the US signal may advance the sensitivity of ultrasonography and exploit the dimension of US imaging of tumor at the molecular level. In this study, we developed CaCO3/pul-PCB (CPP) hybrid nanoparticles with hepatoma-targeting pullulan decorating on the surface through a mineralization route using the pullulan- graft-poly(carboxybetaine methacrylate) (pul-PCB) copolymer as a modifier. This particle was stable in blood physiological pH and generated echogenic CO2 bubbles under tumoral acidic conditions, which enabled the US signal enhancement. Upon intravenous injection, CPP hybrid nanoparticles accumulated efficiently in tumor tissue and exhibited sixfold contrast enhancement in 35 min at the tumor site in the hepatoma-bearing mice model. By contrast, there was barely any signal change in normal liver tissue. Therefore, the presented CPP hybrid nanoparticle is a promising contrast agent for effective US imaging of hepatoma.