BACKGROUND:Surveillance recommendations for postoperative high-risk colorectal bone metastases patients remain in a gray area of guidelines. We aimed to develop a risk stratification system to select ideal candidates for follow-up of colorectal bone metastases status. METHODS:Postoperative colorectal cancer patients were included to develop a risk-scoring system to predict bone metastases. Risk scores were calculated based on the predictive factors for bone metastases, which were identified using the Cox proportional hazard regression model. Kaplan-Meier curves visualize the differences between risk groups. RESULTS:Eight risk factors (age, lymph node metastasis, pathologic tumor deposit, KRAS mutation status, suspicious retroperitoneal lymph node metastasis, lung metastasis status, largest thickness of colorectal cancer lesion, largest short diameter of lymph node) were predictors of colorectal bone metastases and incorporated into the risk scoring system, and the patients were categorized into 2 risk groups. In the low-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 2.4%, 4.6%, and 3.7%, respectively, whereas in the high-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 15.6%, 29.9%, and 44.4%, respectively. The risk scoring system exhibited a C-index of 0.706, 0.795, and 0.841 in 1, 3, and 5 years, respectively. The Kaplan-Meier curve demonstrates that the incidence of colorectal bone metastases was higher in the high-risk group than in the low-risk group (50.5% vs 11.4%, P < .001). CONCLUSION:This risk-scoring system may be valuable in predicting colorectal bone metastases in colorectal cancer patients, and we suggest that colorectal bone metastases status surveillance be added in the high-risk group.

Background and aims The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI + HCC and investigate the underlying immune infiltration patterns with radiomics features. Methods Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI + HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE + macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. Results Elevated levels of APOE+ macrophages and iCAFs were detected in MVI + HCC. There was a strong correlation between the infiltration of APOE + macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE + macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE + macrophages and iCAFs. Conclusion This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI + HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE + macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI + HCC.

AIM:To investigate the occurrence of mosaicism in epilepsy probands and their parents using amplicon-based deep sequencing (ADS).METHODS:Patients were recruited from the outpatient of Peking University First Hospital. Two hundred and sixty-four probands with pathogenic variants tested by next-generation sequencing (NGS) were enrolled.RESULTS:Mosaic variants were detected in seventeen disease-associated genes from 20 probands, 5 paternal, and 6 maternal parents. The frequency of mosaicism was 11.74% (31/264). Mosaicism in 11 genes was identified from 20 probands with the mutant allelic fractions (MAFs) of 12.95-38.00% in autosomal dominant genes. Five paternal mosaicisms were identified in genes with a MAF of 6.30-20.99%, and six maternal mosaic individuals with a MAF of 2.07-21.90%. Only four mosaic parents had milder seizure history. The affected sibling had the same phenotype consistent with that of the proband, who inherited the variant of SLC1A2 or STXBP1 from their unaffected mosaic mothers, respectively.INTERPRETATION:Mosaic phenomenon is not rare in families with epilepsy. Phenotypes of mosaic parents were milder or normal. Mosaicism detection is helpful to identify the mutation origin and it provides a theoretical basis for prenatal diagnosis of family reproduction. ADS is a reliable way of mosaicism detection for clinical application.

Aim We performed a comparative study to investigate the efficacy of closed system transfer devices (CSTDs) on the safe handling of injectable hazardous drugs (HDs). Methods The exposure assessments of cyclophosphamide and cytarabine were performed under traditional or CSTDs. For preparation activity, chemotherapy contamination samples on protective equipment (such as gloves and masks) were collected. The contamination analysis was performed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). A 6-item form was distributed monthly (form M1–M6, total 6 months) to assess the pharmacists' experience on ergonomics, encumbrance, and safety impression. Results Totally, 96 wiping samples were collected throughout the study. The numbers of contaminated cyclophosphamide samples reduced under CSTD were −37.8, −41.6, −67.7, −47.3, and −22.9% and cytarabine were −12.3, −12.1, −20.6, −69.6, and −56.7% for left countertop, right countertop, medial glass, air-intake vent and door handle, as compared to traditional devices. The reduction was similar to pharmacist devices, i.e., −48.2 and −50.0% for masks and gloves cyclophosphamide contamination, −18.0 and −42.4% for cytarabine. This novel system could improve contamination on dispensing table, transfer container, and dispensing basket by −16.6, −6.0, and −22.3% for cyclophosphamide and −28.5, −22.5, and −46.2% for cytarabine. A high level of satisfaction was consistently associated with ergonomics for CSTD during the compounding process. Meanwhile, a slightly decreased satisfaction on ergonomics, encumbrance, and safety impression was observed for the traditional system between M2 and M3. Conclusion Closed system transfer devices are offering progressively more effective alternatives to traditional ones and consequently decrease chemotherapy exposure risk on isolator surfaces.

Introduction Painful diabetic peripheral neuropathy (PDN) is a growing public health problem in China. Despite recent progress in treatment, there has been no nationwide study evaluating current medical practices and compliance with treatment guidelines. The primary aims of this study are to investigate the clinical characteristics and treatment practices for PDN and associated anxiety and depression in China. Methods and analysis Painful Diabetic Peripheral Neuropathy Study of Chinese OutPatiEnts is a cross-sectional, multicentre registry study with a target sample size of approximately 1500 people experiencing PDN. People with PDN will be treated according to current guidelines and local practices. The demographics, medical histories, Visual Analogue Scale pain scores, Patient Health Questionnaire-9 results, Generalised Anxiety Disorder-7 scores and therapies will be recorded to evaluate clinical characteristics of PDN and current treatment practices for pain, anxiety and depression. Ethics and dissemination Ethical approval has been obtained from the Peking University Third Hospital Medical Science Research Ethics Committee (2018–182).The results of this study will be disseminated through peer-reviewed publications and scientific presentations. Trial registration number NCT03520608

In this study, zeolite-templated mesocellular graphene foam was facilely synthesized by pyrolysis under different temperatures for oxygen reduction reaction. Investigations found that MGF can be regulated with different structure properties by controlling the pyrolysis temperature, where the MGF-900 (pyrolyzed under 900 °C) possessed a large BET specific surface area (619 m2 g−1), a hierarchically micro–meso–macroporous carbon framework, and a better balance between conductivity and active sites than the other counterparts (MGF-800 and MGF-1000). As a result, MGF-900 had the most excellent catalytic activity, the most positive onset potential of − 0.1 V and the highest current density of 5.01 mA cm−2 among the different samples and many other reported carbon-based catalysts. More importantly, despite no heterogeneous atoms doping, the catalytic activity of MGF-900 was nearly equal to that of commercial Pt/C catalyst. Regarding tolerance and stability, MGF-900 behaved even better. Therefore, as a superior metal-free electrocatalyst, MGF-900 is proved to be well applied in highly efficient oxygen reduction reaction.

PURPOSE:To investigate the significance of MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) for identifying the expression of cytokeratin 19 (CK-19) in patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) before surgery. PATIENTS AND METHODS:The study enrolled 174 patients pathologically confirmed to have cHCC-CCA according to the 2019 WHO classification. The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the CK-19-positive and CK-19-negative cHCC-CCA groups. RESULTS:One hundred seventy-four patients (mean age, males vs females: 56.6 ± 10.0 years vs 54.7 ± 14.2 years) were evaluated. The presence of mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement was significantly higher in the CK-19-positive group (all p < 0.05), while nonrim arterial phase hyperenhancement (APHE) was more common in the CK-19-negative group (p = 0.04). The univariate analysis showed that hepatitis B virus infection, CEA > 5 ng/mL, tumor size, nonrim APHE, mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement were significant risk factors for CK-19-positive cHCC-CCA (all p < 0.05). Unfortunately, the multivariate analysis revealed that only corona enhancement (OR = 2.359, p = 0.03) was an independent risk factor associated with CK-19-positive cHCC-CCA. CONCLUSION:Corona enhancement is significantly correlated with CK-19 positivity in patients with cHCC-CCA.

Mutations in ITM2B have been found to be associated with familial Danish dementia (FDD) and familial British dementia (FBD). Here, we describe a patient with dementia caused by a novel ITM2B p.*267Leuext*11 mutation. The patient presented with dementia, ataxia, deafness, and paraplegia. Amyloid PET and Tau PET showed abnormal deposition of amyloid and tau protein in brain. Summarized from previous 26 FBD and FDD cases, the clinical phenotype of ITM2B; p.*267Leuext*11 mutation in ITM2B is different from the features of FBD and FDD. Our findings increased genetic knowledge of familial dementia and extend the ethnic distribution of ITM2B mutations.

Modification of proteins with 4-hydroxynonenal (HNE) is known to alter the function of proteins and regulate the associated biological processes in eukaryotic cells. The development of mass spectrometry (MS) makes high-throughput analysis of HNE modification accessible. However, the identification of HNE modification is still hampered by the low frequency of this modification. Therefore, only a limited number of HNE modification sites have been identified. The enrichment of HNE-modified peptides is critical for the MS analysis of this modification because of its low abundance. Herein, we explored a novel strategy for specifically extracting the HNE-modified peptides using fluorous derivatization through oxime click chemistry combined with following fluorous solid-phase extraction (FSPE). This oxime click chemistry-based derivatization is highly efficient (with a yield of almost 100%) and fast (30 min). Because of the hydrophobicity of the fluorous tag, the signal of fluorous-derivatized HNE-modified peptides was greatly enhanced, making the detection of HNE-modified peptides sensitive. The FSPE further allowed the selective enrichment of fluorous-derivatized HNE-modified peptides from salt solutions and complex mixtures with specificity. Finally, 673 HNE modification sites (607 histidine sites, 60 cysteine sites, 5 lysine sites, and 1 arginine site) on 661 HNE-modified peptides mapped to 432 proteins were successfully identified using this novel approach, which presented the largest data set of HNE modification in MCF-7 cells. Three identified proteins were validated by Western blotting.

Matrix assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an increasingly important technique for detection and spatial localization of phospholipids on tissue. Due to the high abundance and being easy-to-ionize of phosphatidylcholine (PC), therefore, selecting matrix to yield signals of other lipids has become the most crucial factor for a successful MALDI-IMS analysis of phospholipids. Herein, graphene oxide (GO) was proposed as a new matrix to selectively enhance the detection of other types of phospholipids that are frequently suppressed by the presence of PC in positive mode. Compared to the commonly used matrix DHB, GO matrix significantly improved signalto- noise ratios of phospholipids as a result of its high desorption/ionization efficiency for nonpolar compounds. Also, GO afforded homogeneous crystallizations with analytes due to its monolayer structure and good dispersion, resulting in better reproducibility of shot-to-shot (CV < 13%) and spotto- spot (CV < 14%) analysis. Finally, GO matrix was successfully applied to simultaneous imaging of PC, PE, PS and glycosphingolipid in the mouse brain, with a total of 65 phospholipids identified.

Dispersed incorporation of functional nanoparticles into ordered mesopores to exert their synergistic properties has shown a promising application, but proved to be a challenging task. Herein, a facile strategy based on solid-phase transformation of the template into polymer-coated carbonaceous nanodots (pCNDs) is used for direct synthesis of multifunctional mesoporous silica nanospheres (MFMSNs) incorporated with dispersed fluorescent carbon nanodots. The homogeneous pCNDs incorporated into mesoporous silica nanospheres (MSNs) can simultaneously act as the nontoxic fluorescence probe for highly efficient fluorescence imaging and also anchoring sites for anticancer drug loading. On the basis of the special hydrophobic π–π/electrostatic interaction between the confined pCNDs in MFMSNs and the aromatic drug molecules, MFMSNs could also function as an advanced drug carrier for pH-triggered drug release. The very simple strategy suggests new insights for synthesizing multifunctional mesoporous nanomaterials and extends the biomedical functions of traditional MSN-based nanovehicles for future biomedical applications.

A facile one-step solvothermal method was developed for the homogeneously confined growth of ultra-small (∼1.5 nm) and monodispersed 2H phase MoS2 nanodots into mesoporous silica nanoparticles (MSNs).

A simple method was developed to synthesize Ag@graphene nanocomposites with rough Ag nanoparticles (AgNPs) conjugated with graphene nanosheets, and the nanocomposites could be used as substrates for effective surface-enhanced Raman spectroscopy (SERS) of fluorescent anticancer drug (Dox) since they could not only enhance the Raman signals but also suppress the fluorescent signals. (C) 2016 Elsevier B.V. All rights reserved.

Magnetic sludge with the unique flexibility, low thermal conductance and plentiful adsorption sites was fabricated for highly efficient As/Sb removal.

A facile co-calcination strategy with simultaneous N-doping, carbon graphitization, and palladium ion (Pd2+) reduction under high temperature was used to derive Pd nanoparticles budded on N-doped ordered mesoporous graphitic carbon nanospheres (Pd/N-MCN). Pd/N-MCN was exploited as a cathode catalyst for the oxygen reduction reaction (ORR). It demonstrated strong stability with a relative current of 95% still persisting after 40 000 s. Most importantly, hybrids exhibited superior methanol tolerance, remaining stable after the addition of 2M methanol in electrolyte. The outstanding performance of Pd/N-MCN in ORR could be attributed to its ordered mesopores, large surface area, homogeneous budding of abundant Pd active sites, graphitization generated by Pd catalysis, and the synergistic effects of Pd nanoparticles strongly coupled to N-MCN. (C) 2015 Published by Elsevier Ltd.

The use of environmental waste products as materials for the production of energy is an extremely attractive prospect for both economic and social development. Sludge flocs (SFs) are environmental waste products that are difficult to handle. We used these SFs as a source of carbon and nitrogen for the preparation of N-doped mesocellular graphene foam (SF-NMGF) via a simple one-step pyrolysis method. The particular composition and structure of the SFs meant that the resultant SF-NMGF had a large Brunauer-Emmett-Teller surface area and consisted of a graphitic framework surrounded by ultrathin nanosheets. The material contained foam-like mesopores with a size centred at about 15 nm and the N was incorporated homogeneously with a high percentage (40.5 at%) of graphitic-N. As a result of these unique properties, the SF-NMGF had an excellent electrocatalytic activity with 4e when used as a metal-free catalyst for the oxygen reduction reaction (ORR). Specifically, the prepared SF-NMGF catalyst exhibited a high diffusion-limited current, superior durability and better immunity towards methanol crossover for the ORR in alkaline solution than a commercial 20 wt% Pt/C catalyst. The synthesis of the SF-NMGF can be scaled up at low cost, which will be beneficial for both sludge handling and the development of materials for the ORR.

The electrochemical oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) are of great interest since they are involved in energy conversion between fuel and electricity. Here, we developed a bifunctional MnO2/graphene/carbon nanotube that is free of noble metals and that could be a promising candidate electrocatalyst for these oxygen reduction and evolution reactions. It was shown to be able to act as an efficient cathode catalyst for the ORR, having a positive half-wave potential that differs by only similar to 55 mV from that of commercial Pt/C, and a high cathodic current density that is comparable to that of the Pt/C catalyst. Moreover, the hybrid exhibited superior durability with nearly no decay in ORR activity even after 10 000 s of continuous operation in 0.1 M KOH, while Pt/C shows a 20% decrease in the activity. Most importantly, the hybrid was also shown to be highly active for the OER. These observations showthis hybrid to be a high-performance non-preciousmetal-based bi-catalyst for both the ORR and OER.

Novel magnetic silica nanoparticles functionalized with layer-by-layer detonation nanodiamonds (dNDs) were prepared by coating single submicron-size magnetite particles with silica and subsequently modified with dNDs. The resulting layer-by-layer dND functionalized magnetic silica microspheres (Fe3O4@SiO2@[dND](n)) exhibit a well-defined magnetite-core-silica-shell structure and possess a high content of magnetite, which endow them with high dispersibility and excellent magnetic responsibility. Meanwhile, dNDs are known for their high affinity and biocompatibility towards peptides or proteins. Thus, a novel convenient, fast and efficient pretreatment approach of low-abundance peptides or proteins was successfully established with Fe3O4@SiO2@[dND](n) microspheres. The signal intensity of low-abundance peptides was improved by at least two to three orders of magnitude in mass spectrometry analysis. The novel microsphere also showed good tolerance to salt. Even with a high concentration of salt, peptides or proteins could be isolated effectively from samples. Therefore, the convenient and efficient enrichment process of this novel layer-by-layer dND-functionalized microsphere makes it a promising candidate for isolation of protein in a large volume of culture supernatant for secretome analysis. In the application of Fe3O4@SiO2@[dND](n) in the secretome of hepatoma cells, 1473 proteins were identified and covered a broad range of pI and molecular weight, including 377 low molecular weight proteins.

Tumor-specific therapeutic platforms designed for combined tumor therapy has recently received wide attention. In this work, a new HB5 aptamer-functionalized mesoporous silica–carbon based doxorubicin (DOX)-loaded system (MSCN-PEG-HB5/DOX) was successfully constructed and characterized for chemo-photothermal combined therapy of human epithelial growth factor receptor 2 (HER2)-positive breast cancer cells. The in vitro release result showed that MSCN-PEG-HB5/DOX exhibited pH-sensitive and NIR-triggered release manner. HB5-modified nanoparticles showed significant higher cellular uptake in HER2-positive breast cancer cells (SK-BR-3) but not in normal breast epithelial cells (MCF-10A), compared to unmodified counterparts. The intracellular uptake of functional nanoparticles was mainly based on the receptor-mediated mechanism which was energy-dependent. Cytotoxicity experiments demonstrated that combined therapy induced highest cell killing effect compared to chemotherapy and photothermal therapy alone. The combination index (CI) was 0.253 indicating the synergistic effect of chemotherapy and photothermal therapy. These findings suggested that MSCN-PEG-HB5/DOX was a potential chemo-photothermal therapeutic platform targeting to HER2-positive breast cancers.