Sex Estimation of Medial Aspect of the Ischiopubic Ramus in Adults Based on Deep Learning.

OBJECTIVES: To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population. METHODS: The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc. RESULTS: When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%. CONCLUSIONS: The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.

Rational design of an oxygen-enriching nanoemulsion for enhanced near-infrared laser activatable photodynamic therapy against hypoxic tumors.

Photodynamic therapy (PDT) has emerged as one of the most promising modalities to treat cancers. However, the hypoxic microenvironment in tumors severely limits the efficiency of PDT. IR780 is a near-infrared light activatable photosensitizer for PDT. It has attracted intensive attention owing to its intriguing properties such as mitochondria-targeting ability and fluorescence imaging capability. Nevertheless, its application in tumor treatment is hampered by its low aqueous solubility and poor stability. To address these obstacles, here we designed a novel hierarchical nanoplatform containing a uniquely stable high loading capacity oxygen carrier (perfluoropolyether, in short, PFPE) and IR780. This nanoplatform (IR780-P/W NE, in abbreviation for IR780-PFPE-in-water nanoemulsion) has no detectable dark cytotoxicity. It not only improves the aqueous solubility and stability of IR780, but also transports oxygen to relieve hypoxia and boosts the efficiency of near-infrared light triggered PDT via augmentation of reactive oxygen species generation. Particularly, the innovative nanosized oxygen carrier developed in this research, P/W NE, is a potential universal platform for loading hydrophobic photosensitizers (including but not limited to IR780), sonosensitizers, or radiosensitizers, and simultaneously improving the therapeutic efficacy. Our results highlight the intriguing potential of the developed nanoemulsions for mitigating tumor hypoxia and enhancing the efficiencies of oxygen-dependent therapies including PDT, sonodynamic therapy, radiotherapy, and so on.

RET S409Y Germline Mutation and Associated Medullary Thyroid Carcinoma.

Background: Inherited medullary thyroid carcinoma (MTC) is primarily caused by RET mutations that are commonly localized in exons 5, 8, 10, 11, and 13-16. In this study, we report pedigrees for individuals with MTC that harbor a germline S409Y variant within exon 6 of the RET proto-oncogene. Methods: Targeted sequencing was used to diagnose four apparently sporadic MTC index cases carrying the germline RET S409Y (c.1226 C>A) variant. Subsequently, 27 relatives of these individuals underwent clinical and genetic assessments and/or thyroid surgery. Furthermore, in silico analyses and in vitro assays were performed to predict or verify the potential oncogenic activity of the S409Y variant. Results: Overall, 15 of 31 participants were found to carry the RET S409Y variant. Of these, 6 presented with isolated MTC (mean age 50.2 years; range 41-75 years), of which 3 presented with neck lymph node metastases and 2 presented with distant liver or lung metastases. Among the remaining 9 carriers, 3 (mean age 56 years; range 41-76 years) had elevated serum calcium-stimulated calcitonin (sCtn) or concurrent marginally elevated serum calcitonin (Ctn) levels, whereas the other 6 (mean age 37.5 years; range 14-52 years) exhibited typical Ctn/sCtn levels (p < 0.05). None of the 15 carriers in these 4 families presented clinical evidence of pheochromocytoma, hyperparathyroidism, or Hirschsprung's disease. In silico analyses revealed that S409Y was a "possibly damaging" mutation that could affect the RET protein inter-domain interface. An in vitro assay revealed that the phosphorylation level of RET tyrosine 905 was relatively higher in the RET S409Y mutant than in wild-type (WT) RET. Moreover, transfection of HEK 293 cells with S409Y enhanced the phosphorylation activity of AKT, ERK pathways, and it increased cell proliferation compared with WT RET, but to a lesser degree than that for the RET C618Y and C634Y mutations. Conclusions: This study demonstrates that the novel germline RET S409Y variant is likely pathogenic and is associated with lower penetrance of MTC than that for the C618Y and C634Y mutations. Individuals with S409Y should be managed using a personalized approach, and additionally, "at-risk" family members should be evaluated. Additional studies are needed to elucidate the correlation between the S409Y mutation and multiple endocrine neoplasia type 2-specific tumors.

Prognostic significance of locally invaded sites and tissue types in patients with nasal extranodal natural-killer/T-cell lymphoma: a single-center retrospective analysis.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL. METHODS: We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients' overall survival (OS). RESULTS: Of the 86 patients, 71 (82.6%) experienced invasion of AS, 22 (25.6%) of soft tissue, and 26 (30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ = 4.105, P = 0.043) or brain involvement (Log rank χ = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ = 10.390, P = 0.001) or bones (Log rank χ = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. CONCLUSIONS: Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.

The Clinical Spectrum of Multiple Endocrine Neoplasia Type 2A with Cutaneous Lichen Amyloidosis in Ethnic Han Chinese.

This study systematically reviewed previous literatures and analyzed the genotype-phenotype relationship between the multiple endocrine neoplasia type 2A (MEN 2A)-cutaneous lichen amyloidosis (CLA) and RET/OSMR/IL31RA mutations. RET/OSMR/IL31RA screening was performed on 8 RET-carriers from 3 independent Chinese MEN 2A families. Besides, 51 MEN 2A-CLA patients in 116 RET carriers from literatures were clustered and analyzed. Our results indicated that almost all MEN 2A-CLA patients exhibited CLA which was located in the scapular region and carried RET mutation at codon 634. Meanwhile, we firstly described MEN 2A-CLA here in Chinese Han patient with RET p.C634F mutation.

Self-doped rutile titania with high performance for direct and ultrafast assay of H2O2.

Detection of H2O2 is important for the applications in environmental protection, pharmaceutical industries, food production, and clinical control. Current colorimetric assay of H2O2 based on enzyme or nanomaterials always needs TMB or other peroxidase substrate as coloration species. Furthermore, the corresponding response time including incubation process is in order of minute. In this study, we report on the synthesis of heavily Ti(3+)-doped TiO2 composed of spherelike nanoparticles by pulsed laser ablation method. This TiO2 can directly detect H2O2 without using TMB or any other peroxidase substrate and is free from incubation process. In addition, the detection sensitivity is compatible with or better than that of the natural enzyme or other nanomaterials. Hence, the self-doped TiO2 nanoparticles provide a novel, direct, ultrafast approach for H2O2 assay application.

Trans-3,4,5,4'-tetramethoxystilbene, a resveratrol analog, potently inhibits angiogenesis in vitro and in vivo.

AIM: Trans-3,4,5,4'-tetramethoxystilbene (DMU-212) has shown strong antiproliferative activities against a variety of cancer cells. The aim of this study was to investigate the anti-angiogenic effects of DMU-212 in vitro and in vivo. METHODS: Human umbilical vein endothelial cells (HUVECs) were used in this study. Cell viability was studied with MTT assay, and cell apoptosis was evaluated using TUNEL assay and morphological observation. The expression of the related genes and proteins was analyzed with qRT-PCR and Western blot, respectively. Angiogenesis of HUVECs were studied using cell migration and capillary-like tube formation assays in vitro, and mouse Matrigel plug assay and chick chorioallantoic membrane (CAM) assay in vivo. The tyrosine kinase activities of VEGFR1 and VEGFR2 were measured using commercial kits. RESULTS: DMU-212 (5-80 µmol/L) significantly inhibited VEGF-stimulated proliferation of HUVECs (IC50 value was approximately 20 µmol/L), and induced apoptosis. Furthermore, DMU-212 concentration-dependently inhibited VEGF-induced migration of HUVECs and capillary-like structure formation in vitro. DMU-212 also inhibited VEGF-induced generation of new vasculature in Matrigel plugs in vivo with significantly decreased area of infiltrating CD31-positive endothelial cells, and inhibited newly formed microvessels in chick CAMs. Moreover, DMU-212 concentration-dependently suppressed VEGF-induced phosphorylation of VEGFR2, and inhibited phosphorylation of multiple downstream signaling components in the VEGFR2 pathway, including c-Src, FAK, Erk1/2, Akt, mTOR, and p70S6K in HUVECs. DMU-212 had no effect on VEGF-induced phosphorylation of VEGFR1. CONCLUSION: DMU-212 is a potent inhibitor of angiogenesis that exerts anti-angiogenic activity at least in part through the VEGFR2 signaling pathway.

Treatment of hyperlipidemia with a modified low density lipoprotein apheresis system with dextran sulfate.

Many low density lipoprotein (LDL) apheresis systems have been applied to patients with hyperlipidemia, but these systems usually work on the basis of complicated equipment and the cost of treatment is expensive. In order to achieve effective treatment of hyperlipidemia at a lower cost, we developed a new LDL apheresis system with dextran sulfate (LAS-DS). In this study, 50 patients with hyperlipidemia were treated 120 times with the new LAS-DS. In each treatment, 600 +/- 100 mL of plasma (equal to approximately 25% of the total plasma of patients) was collected by apheresis, and DS solution and calcium chloride solution were added into the collected plasma as LDL absorber and catalyzer, respectively. DS selectively binds LDL cholesterol (LDL-C) under the catalysis of calcium ion and the LDL-C-DS complex is removed by centrifugation. The treated plasma was transfused back into the patients and the excessive calcium in the plasma was removed by the cation exchange column integrated in the transfusion set. After treatment with our new system, the acute mean LDL-C reduction was 97% in the apheresis plasma of hyperlipidemia patients. The corresponding reduction was 55.2% and 69.4% for total cholesterol and total triglyceride. There were insignificant reductions of high density lipoprotein cholesterol (HDL-C) and albumin. The new LDL apheresis system with DS that we developed is very simple to operate without relying on complicated equipment, and it can achieve significant clinical results at a much lower cost compared with existing systems. Based on this study we think the new system can provide a safe, effective and much cheaper means for the treatment of hyperlipidemia patients.

[Efficiency of total parathyroidectomy and autotransplantation in 31 patients with uremic hyperparathyroidism].

OBJECTIVE: To analyse the efficacy of total parathyroidectomy with autotransplantation (total PTX + AT) in treating uremic secondary hyperparathyroidism and to discuss the relevant medical treatment used. METHODS: The clinical data of 31 patients with uremic SHPT admitted into our hospital from 1996-2005 were analysed with respect to total PTX + AT. RESULTS: The period of hemodialysis were for the patients was on the average 9.2 years. There were 22 male and 9 female with an average age of 42.4 (31 - 67) years. The clinical manifestations consisted of osteoarticular pain in 83.9%, fractures in 35.5%, soft tissue and vascular calcification in 45.2% and pruritus in 80.6%. Laboratory examination yielded the following results: haematocrit 0.25 +/- 0.04, serum Ca (2.61 +/- 0.35) mmol/L, serum P (2.14 +/- 0.31) mmol/L, plasma total alkaline phosphatase (AKP) (885 +/- 335) U/L and parathyroid hormone (iPTH) (1811 +/- 879) ng/L (700 - 2500 ng/L). Cervical ultrasonography and/or emission computed tomography showed 2 - 4 hyperplastic glands. All of the patients showed no response to medical treatment including vitamin D. Total PTX + AT was performed on the 31 cases. Clinical symptoms and signs markedly improved after operation in 1 to 2 weeks. However, fracture and ectopic calcification showed no improvement. Plasma iPTH decreased rapidly (< 200 ng/L) postoperatively in 1 to 2 days. Serum Ca and P returned to normal. AKP was corrected in 1 to 3 months. CONCLUSION: Total parathyroidectomy with autotransplantation is an effective treatment for severe uremic secondary hyperparathyroidism patients.

Assembly of azido- or cyano-bridged binuclear complexes containing the bulky [Mn(phen)2]2+ building block: syntheses, crystal structures, and magnetic properties.

Two new cyano-bridged heterobinuclear complexes, [Mn(II)(phen)2Cl][Fe(III)(bpb)(CN)2] x 0.5CH3CH2OH x 1.5H2O (1) and [Mn(II)(phen)2Cl][Cr(III)(bpb)(CN)2] x 2H2O (2) [phen = 1,10-phenanthroline; bpb(2-) = 1,2-bis(pyridine-2-carboxamido)benzenate], and four novel azido-bridged Mn(II) dimeric complexes, [Mn2(phen)4(mu(1,1)-N3)2][M(III)(bpb)(CN)2]2 x H2O [M = Fe (3), Cr (4), Co (5)] and [Mn2(phen)4(mu(1,3)-N3)(N3)2]BPh4 x 0.5H2O (6), have been synthesized and characterized by single-crystal X-ray diffraction analysis and magnetic studies. Complexes 1 and 2 comprise [Mn(phen)2Cl]+ and [M(bpb)(CN)2]- units connected by one cyano ligand of [M(bpb)(CN)2]-. Complexes 3-5 are doubly end-on (EO) azido-bridged Mn(II) binuclear complexes with two [M(bpb)(CN)2]- molecules acting as charge-compensating anions. However, the Mn(II) ions in complex 6 are linked by a single end-to-end (EE) azido bridging ligand with one large free BPh4(-) group as the charge-balancing anion. The magnetic coupling between Mn(II) and Fe(III) or Cr(III) in complexes 1 and 2 was found to be antiferromagnetic with J(MnFe) = -2.68(3) cm(-1) and J(MnCr) = -4.55(1) cm(-1) on the basis of the Hamiltonian H = -JS(Mn)S(M) (M = Fe or Cr). The magnetic interactions between two Mn(II) ions in 3-5 are ferromagnetic in nature with the magnetic coupling constants of 1.15(3), 1.05(2), and 1.27(2) cm(-1) (H = -JS(Mn1)S(Mn2)), respectively. The single EE azido-bridged dimeric complex 6 manifests antiferromagnetic interaction with J = -2.29(4) cm(-1) (H = -JS(Mn1)S(Mn2)). Magneto-structural correlationship on the EO azido-bridged Mn(II) dimers has been investigated.

[Fe(bpb)(CN)2]- as a versatile building block for the design of novel low-dimensional heterobimetallic systems: synthesis, crystal structures, and magnetic properties of cyano-bridged Fe(III)-Ni(II) complexes [(bpb)(2-) = 1,2-bis(pyridine-2-carboxamido)benzenate].

A dicyano-containing [Fe(bpb)(CN)2]- building block has been employed for the synthesis of cyano-bridged heterometallic Ni(II)-Fe(III) complexes. The presence of steric bpb(2-) ligand around the iron ion results in the formation of low-dimensional species: five are neutral NiFe2 trimers and three are one-dimensional (1D). The structure of the 1D complexes consists of alternating [NiL]2+ and [Fe(bpb)(CN)2]- generating a cyano-bridged cationic polymeric chain and the perchlorate as the counteranion. In all complexes, the coordination geometry of the nickel ions is approximately octahedral with the cyano nitrogen atoms at the trans positions. Magnetic studies of seven complexes show the presence of ferromagnetic interaction between the metal ions through the cyano bridges. Variable temperature magnetic susceptibility investigations of the trimeric complexes yield the following J(NiFe) values (based on the spin exchange Hamiltonian H = -2J(NiFe) S(Ni) (S(Fe(1)) + S(Fe(2))): J(NiFe) = 6.40(5), 7.8(1), 8.9(2), and 6.03(4) cm(-1), respectively. The study of the magneto-structural correlation reveals that the cyanide-bridging bond angle is related to the strength of magnetic exchange coupling: the larger the Ni-N[triple bond]C bond angle, the stronger the Ni- - -Fe magnetic interaction. One 1D complex exhibits long-range antiferromagnetic ordering with T(N) = 3.5 K. Below T(N) (1.82 K), a metamagnetic behavior was observed with the critical field of approximately 6 kOe. The present research shows that the [Fe(bpb)(CN)2]- building block is a good candidate for the construction of low-dimensional magnetic materials.