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Most seizures in critical ill patients are non-convulsive, and some patients may develop non-convulsive status epilepticus (NCSE), a state of continuous or repetitive seizures without convulsions. With the growing use of continuous electroencephalogram (EEG) monitoring in neuro-intensive care units, non-convulsive seizure (NCS) and NCSE are increasingly diagnosed in patients with impaired consciousness, and progress has been made in identifying various EEG characteristics of NCS/NCSE. Epidemiological studies have contributed to a better understanding of etiologies and risk factors for NCS and NCSE. However, sufficient clinical trials about the treatment of NCS and NCSE are still lacking. The appropriate level of aggressiveness in the treatment of NCSE is still debated, particularly with regard to the use of anesthetics in patients with refractory NCSE. In this review, we summarize the EEG, clinical, epidemiological, diagnostic and therapeutic knowledge of NCS and NCSE in the neuro-intensive care setting in detail.

Aim To introduce the novel use of lauromacrogol for cesarean scar pregnancy (CSP), and to compare the clinical efficacy and safety of curettage combined with ultrasound-guided sclerosant injection (USI) and curettage following uterine artery embolization (UAE) in the treatment of CSP. Methods CSP patients undergoing curettage combined with USI (n = 72) from December 2014 to May 2020 were compared to patient with curettage following UAE (n = 72).The basic clinical findings and clinical outcomes were reviewed between the two groups. Results For USI group, 69 patients underwent successful treatment (95.8% success rate), while the number of cured patients for the UAE group was 70 (97.2% success rate). Differences between USI group and UAE group in intraoperative blood loss (10.0 [10.0-20.0] vs. 10.0 [10.0-20.0] mL) and time for serum β human chorionic gonadotropin (β-hCG) to reduce to normal (28.0 [21.0-40.0] vs. 28.0 [21.0-35.0] days) were not statistically significant. The hospital stay for USI group was significantly shorter than that for UAE group (4.0 [4.0-6.0] vs. 6.0 [5.0-7.0] days, respectively). Statistically significant decreases were noted in hospitalization expenses and adverse events in USI group, compared to UAE group. There was no difference in live birth rate between the two groups with fertility intentions during the follow-up. Conclusion For treatment of CSP, curettage combined with USI yielded clinical results comparable to those of curettage following UAE. Curettage combined with USI was associated with lower hospitalization expenses, shorter hospital stay and less complications, and it merited an effective and safe treatment for CSP.

The accuracy of 3-dimensional (3D) optical devices for facial soft-tissue measurement is essential to the success of clinical treatment in stomatology. The aim of the present systematic review was to summarize the accuracy of 3D optical devices used for facial soft-tissue assessment in stomatology.An extensive systematic literature search was performed in the PubMed/MEDLINE, Embase, Scopus and Cochrane Library databases for studies published in the English language up to May 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Peer-reviewed journal articles evaluating the facial soft-tissue morphology by 3D optical devices were included. The risk of bias was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies-2 guidelines by the 2 reviewers. The potential publication bias was analyzed using the Review Manager software.The query returned 1853 results. A total of 38 studies were included in this review. Articles were categorized based on the principle of devices: laser-based scanning, structured-light scanning, stereophotogrammetry and red, green, blue-depth camera.Overall, the 3D optical devices demonstrated excellent accuracy and reliability for facial soft-tissue measurement in stomatology. red, green, blue-depth camera can collect accurate static and dynamic 3D facial scans with low cost and high measurement accuracy. Practical needs and availability of resources should be considered when these devices are used in clinical settings.

To assess the association of single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 1 (VEGFR1) pathways-related genes and the risk of pre-eclampsia.In total 178 pregnant women with pre-eclampsia (case group) and 100 healthy pregnant women (control group) during the third trimester were enrolled. The SNPs of VEGF rs3025039, rs2010963 and VEGFR1 rs3812867, rs55875014 and rs722503 loci were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. The levels of serum VEGF and sVEGFR1 were also determined. And their association with pre-eclampsia was analyzed.The systolic blood pressure, diastolic blood pressure and sVEGFR1 of the case group were significantly higher than those of the control group, while the VEGF level was significantly lower than that in the control group (P0.05). Allelic frequencies of the VEGF (rs3025039, rs2010963) and VEGFR1 (rs3812867, rs55875014, rs722503) have fit the Hardy-Weinberg equilibrium (P0.05). The frequency of T allele of VEGF at rs3025039 locus in the case group was higher than that in the control group (P0.05). There were significant differences in VEGF at rs3025039 locus under dominant and co-dominant models in case group (P0.05). Compared with those with CC, the risk was higher in patients with CT or TT genotypes (P0.05). The systolic and diastolic blood pressure and sVEGFR1 in pre-eclampsia pregnant women with CT or TT genotypes were significantly higher than those with the CC genotype, while their VEGF level was significantly lower (P0.05). No significant difference was found in allelic frequencies of other four loci between the two groups (P0.05).Polymorphisms of rs3025039 locus of VEGF gene is associated with the occurrence of pre-eclampsia. The variant at this locus may affect the activity of VEGF and influence the development of pre-eclampsia.

Based on increasing research evidence, hepatocellular carcinoma (HCC) is heterogeneous, and genetic profiling has led to the identification of multiple subtypes of this disease. To advance our knowledge and the ability to use individualized medicine in the treatment of HCC, it is essential to perform a complete and methodical characterization of various molecular subtypes. The canonical Wnt/β-catenin pathway is an evolutionarily conserved complicated signaling mechanism that plays a role in carcinogenesis and progression of HCC. In this study, we acquired RNA sequencing, somatic mutation, and clinical data from 701 patients from The Cancer Genome Atlas and Gene Expression Omnibus databases and stratified patients into two subgroups: WNT-high and WNT-low. In general, the WNT-high subtype is associated with an immunosuppressive microenvironment, poor prognosis, cancer-related pathways, and a low response to immune checkpoint therapy. We also found that WNT3 is negatively linked to CD8+ T-cell infiltration using multiple immunofluorescence assays. Finally, we developed a WNT-related prognostic model to predict the survival time of patients with HCC. In summary, we developed a new classification scheme for HCC based on Wnt signaling signatures. This classification produced substantial clinical effects, both in terms of assessing patient prognosis and immunotherapy administered to patients with HCC.

This work reported a simple and ultrasensitive label-free method for the detection of hepatitis B virus (HBV) DNA by combining hyperbranched rolling circle amplification (HRCA) with dual-mode detection by inductively coupled plasma mass spectrometry (ICP-MS) and fluorescence using ruthenium complex [Ru(bpy)2dppz]2+ (bpy = 2,2'-bipyridine, dppz = dipyrido [3,2-a:2',3'-c] phenazine) as a dual functional probe. An HBV DNA-initiated HRCA system was designed to realize the highly efficient amplification of HBV DNA with the generation of a mass of dsDNA. Also, the [Ru(bpy)2dppz]2+ probe was then added to intercalate into the dsDNA products, resulting in strong fluorescence recovery of the probe for fluorescence detection. Meanwhile, using a biotin-modified primer in HRCA, the dsDNA-[Ru(bpy)2dppz]2+ complexes could be captured by the avidin-coated 96-well plates, and the captured [Ru(bpy)2dppz]2+ probe was later desorbed by acid for ICP-MS detection. The linear range of the proposed method was 3.5-200 amol L-1 and the limit of detection (LOD) was 1 amol L-1 for ICP-MS detection, while the linear range was 20-500 amol L-1 and the LOD was 9.6 amol L-1 for fluorescence detection. The developed method was applied to human serum sample analysis, and the analytical results coincided very well with those obtained by the real-time polymerase chain reaction (PCR) method. The developed dual-mode label-free detection method was ultrasensitive, simple, and accurate, showing great potential for therapeutic monitoring of HBV infection.

Exosomes, potential biomarkers for liquid biopsy, provide a promising opportunity for early cancer diagnosis in a noninvasive manner. However, direct analysis of exosomes in complicated biological samples is still challenging. Herein, a cholesterol recognition assay was proposed for detection of exosomes by gold nanoparticles (Au NPs) labeling inductively coupled plasma mass spectrometry. Specifically, exosomes were captured by anti-CD63, and then cholesterol-modified rolling circle amplification product was inserted into the membrane of exosomes for signal amplification. Simultaneously, Au NPs-labelled DNA was prepared for labeling and read-out signal. The proposed method achieved the quantification of the exosome concentration in a range of 10-10

Quantification of multiple disease-related microRNAs (miRNAs) is of great significance for clinical diagnosis. Based on the simultaneous multiple element detection ability of inductively coupled plasma-mass spectrometry (ICP-MS) and good specificity of multicomponent nucleic acid enzymes (MNAzymes), a novel and simple method based on the MNAzyme amplification strategy and lanthanide labeling coupled with ICP-MS detection was proposed for the sensitive and simultaneous detection of three miRNAs (miRNA-21, miRNA-155, and miRNA-10b). Specifically, a probe consisting of streptavidin-modified magnetic beads (SA-MBs) and three DNA substrates labeled with lanthanide tags (159Tb/165Ho/175Lu) was constructed. In the presence of target miRNAs, three pairs of MNAzymes were assembled where each pair was hybridized with the corresponding miRNA, and then the substrates on the SA-MBs were cleaved by the activated MNAzymes, continuously releasing the fragment with lanthanide tags. The released lanthanide tags in the supernatant were collected after magnetic separation and analyzed by ICP-MS, realizing the simultaneous quantification of multiple miRNAs. The correlation of the lanthanide tag signal with the miRNA concentration fitted well in a linear model in the range of 50-1000 pmol L-1 (miRNA-21) and 50-2000 pmol L-1 (miRNA-155 and miRNA-10b). The limits of detection for three miRNAs were 11-20 pmol L-1, with the relative standard deviations of 2.2-2.7%. The recoveries of target miRNAs in the human serum and HepG-2 cells were in the range of 87.2-111% and 93.3-111%, respectively. Overall, the method is ideal for the simultaneous quantification of multiple miRNAs with advantages of low spectral interference, high sensitivity, good selectivity, and strong resistance to the complex matrix.

Adenosine triphosphate (ATP), as a high-energy phosphate compound that stores and releases energy in living cells, has an irreplaceable role in many physiological processes and maintenance of biological functions, and can be used as an indicator of many diseases. In this work, a composite nanoprobe, silver nanocluster (AgNC) @ molybdenum disulfide (MoS2), was designed to achieve in situ fluorescence imaging and quantitative analysis of intracellular ATP in HeLa cells by fluorescence spectrometry and inductively coupled plasma mass spectrometry (ICP-MS). The probe was constructed based on the adsorption of DNA-AgNCs by MoS2 nanosheets, and the DNA-AgNCs were prepared with the ATP aptamer as a template, whose fluorescence was initially quenched by MoS2. When the probe was incubated into the cells, intracellular ATP recognized the aptamer sequence and caused the DNA-AgNCs to fall off the MoS2 nanosheets, resulting in fluorescence recovery. Here, AgNCs not only acted as a fluorescence label for imaging, but also as an element tag for quantitative analysis of intracellular ATP with the detection of 107Ag by ICP-MS. The ATP in HeLa cells detected by this method was 24.6 ± 1.7 nmol L−1, which was in good agreement with the test result of the ATP test kit (20.4 ± 0.8 nmol L−1). The proposed method has potential application in medical clinical diagnosis and evaluation of the body’s metabolic level via fluorescence imaging and ICP-MS detection of intracellular ATP.

Objective This is the first clinical study that wants to investigate the treatment patterns, clinical outcomes, and prognostic factors of regorafenib plus PD-1 inhibitors therapy in Chinese elderly patients with advanced colorectal cancer. Methods A cohort of metastatic colorectal cancer patients 60 years or older who received treatment with regorafenib combined with PD-1 inhibitors was included in our analysis. The endpoints included overall survival (OS), progression-free survival (PFS), and prognostic factors. Results In total, 24 patients were enrolled with the median age of 68 years, and 62.5% were female. The median OS and PFS were 15.03 months (95% CI 7.0–23.0) and 4.0 months (95% CI 1.8–6.2), respectively. The objective response rate was 8.3%, and the disease control rate was 70.8%. Patients previously treated with regorafenib had a longer median PFS than those without (6.3 versus 2.8 months). In terms of final daily doses, it showed a trend toward better PFS (median PFS was 10.0 months) in high-dose group (daily dose above 80 mg of regorafenib) compared to low-dose group (daily dose no more than 80 mg of regorafenib) (median PFS was 3.5 months). Conclusions This real-world evidence confirms that Chinese elderly patients with advanced colorectal cancer may benefit from the treatment of regorafenib combined with PD-1 inhibitors, similarly with this combination therapy strategies in all age patients.

Lung squamous cell carcinoma (LSCC) is the most common histological type of primary lung cancer. In this study, we had tested the biological role of TRIM29 in LSCC cells. TRIM29 abundance, the relationships between TRIM29 and E-cadherin and autophagy degradation related proteins in clinical tissues and six cell lines were studied with quantitative real-time PCR test (qRT-PCR) and western blot. TRIM29 overexpression treated HTB-182 cells and knockdown treated NCL-H1915 cells was used for studying cell proliferation, colony formation, migration, invasion, and the expression of epithelial mesenchymal transformation (EMT) associated biomarkers. The relationships between TRIM29 and BECN1 were investigated with western blot. TRIM29 was profoundly overexpressed in LSCC tissues and cells compared with human normal bronchial epithelial cells (HNBE). High TRIM29 expression was closely related to overall survival (OS). TRIM29 overexpression and knockdown affected LSCC activity and the expression of EMT associated biomarkers. TRIM29 can regulate the degradation of E-cadherin and autophagy of LSCC through BECN1 gene, and promote autophagy in HTB-182 and NCL-H1915 cells. Our results revealed that TRIM29 could promote the proliferation, migration, and invasion of LSCC via E-cadherin autophagy degradation. The results are useful for further study in LSCC.

S100 binding protein A16 (S100A16) expression levels are closely associated with microRNA (miRNA) processing. Higher levels of S100A16 are reported during the progression of many cancers. Our study mainly explored the interaction between S100A16 and miR-6884-5p in gastric cancer (GC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the level of S100A16 and miR-6884-5p in GC tissues and cell lines. The si-S100A16, pcDNA-S100A16, miR-6884-5p mimic or inhibitor was transfected into GC cells, and the effects of S100A16 and miR-6884-5p on the proliferation, invasion, and epithelial‐mesenchymal transition (EMT) were explored by qRT-PCR and Western blot assays. Luciferase assays were performed to validate S100A16 as an miR-6884-5p target in GC cells. In our study, we found that the level of miR-6884-5p was significantly decreased and the expression of S100A16 was significantly increased in GC tissues and cell lines. There was a close association between these changes. Knockdown of S100A16 significantly inhibited the proliferation, invasion, and EMT of GC cells. The bioinformatics analysis predicted that S100A16 is a potential target gene of miR-6884-5p, and the luciferase reporter assay confirmed that miR-6884-5p could directly target S100A16. Introduction of miR-6884-5p to GC cells had similar effects to S100A16 silencing. Overexpression of S100A16 in GC cells partially reversed the inhibitory effects of the miR-6884-5p mimic. miR-6884-5p inhibited the proliferation, invasion, and EMT of GC cells by directly decreasing S100A16 expression.

Cancer cells express high levels of programmed death ligand 1 (PD-L1), a ligand of the programmed cell death protein 1 (PD-1) receptor on T cells, allowing tumors to suppress T cell activity. Clinical trials utilizing antibodies that disrupt the PD-1/PD-L1 checkpoint have yielded remarkable results, with anti-PD-1 immunotherapy approved as a first-line therapy for patients with lung cancer. We used CRISPR-based screening to identify regulators of PD-L1 in human lung cancer cells, revealing potent induction of PD-L1 upon disruption of heme biosynthesis. Impairment of heme production activates the integrated stress response, allowing bypass of inhibitory upstream open reading frames in the PD-L1 5′ untranslated region, resulting in enhanced PD-L1 translation and suppression of anti-tumor immunity. We demonstrate that integrated stress-response-dependent PD-L1 translation requires the translation initiation factor eIF5B. eIF5B overexpression, which is frequent in lung adenocarcinomas and associated with poor prognosis, is sufficient to induce PD-L1. These findings illuminate mechanisms of immune checkpoint activation and identify targets for therapeutic intervention. O’Donnell and colleagues report that activation of the integrated stress response in non-small cell lung cancer cells by impairing heme production leads to enhanced PD-L1 translation in an eIF5B-dependent manner.

Background: Radix Stephaniae Tetrandrine (RST), known as FangJi (Pinyin name) in Chinese, is the dried root of Stephania tetrandra S.Moore, and has been prescribed in combination with other herbs to treat cardiovascular diseases and breast cancer in traditional Chinese medicine (TCM) clinical trials. Objective: The aim of the review is to provide a comprehensive evaluation about the application of RST in breast cancer management in TCM clinical trials, its ingredients, and its action on preventing the development of breast cancer in vitro and in vivo studies. Methods: Literature sources used were Pubmed, CNKI.net, Cqvip.com, and the Web of Science. For the inquiry, keywords such as Fangji, breast cancer, clinical trials, Radix Stephaniae Tetrandrine, tetrandrine, and fangchinoline were used in various combinations. About 150 research papers and reviews were consulted. Results: In TCM, RST exhibited the anti-tumor ability through its action on the bladder and lungs through dispersing phlegm and blood stasis. 10 clinical trials were identified which used RST in combination with other herbs to treat breast cancer. On average, the trials were characterized by high efficacy (>85%) and low toxicity. However, most of the clinical trials are characterized as small patient samples, poor design, and different combinations of herbs in prescriptions. To date, more and more compounds have been isolated from this plant. RST exhibited anti-tumor activities by targeting reversing multidrug resistance, inhibiting cell proliferation, inducing apoptosis, preventing tumor angiogenesis, anti-oxidation, anti-inflammation, and enhancing the sensitization and attenuating the toxicity of radiotherapy. Conclusion: The successful applications of RST in TCM clinical trials and preclinical experiments to beating breast cancer will provide potent lead compounds in the identification of novel anti-cancer drugs, which further contributes to the scientific exploration of functions of RST in TCM.

Photosensitive is probably caused by multiple factors including gender, familiar, etc. We aim to study the clinical and EEG features of Chinese Han patients with photosensitivity. A total of 5482 consecutive patients with possible epilepsy from 3 center in China. Of the 73 patients with PPR to IPS, 48 were female. 69.9% patients were evoked by frequency ranged 8 Hz–25 Hz, with accompanying seizures in 13 patients. 6 of 9 patients with eyes closure sensitivity experienced epileptic seizures during IPS. We found some new features: 1) The patients with eyes closure sensitivity apt to experience electro-clinical seizures provoked by IPS; 2) Female epilepsy patients with PPR and ECS maybe difficult to be seizure free. Preventive measures for related seizures should be performed to the patients with generalized PPR, upper threshold evoking frequency, and eyes closure sensitivity when they received the IPS.

An intelligent nursing system for hospital wards is designed. With STM32 as the core and Internet of things technology, the intelligent nursing system can obtain body temperature, heart rate and control all the facilities in the ward by itself through the mobile APP. The intelligent nursing system has the advantages of simple operation, high accuracy of measurement data, stiff stability and good real-time performance. It can not only realize comprehensive real-time health monitoring for patients, but also greatly reduce the workload of nurses and improve work efficiency.

CD142 is expressed on the surface of multiple malignant tumors and contributes to carcinogenesis. However, the role of CD142 in the pathogenesis of gastric adenocarcinoma (GAC) remains unclear. This study aimed to investigate the role of CD142 in GAC carcinogenesis. Our results showed that CD142 expression was significantly increased in GAC cancer tissues, especially in those with significant invasion or metastasis. The invasion and migration of CD142-positive SNU16 cells was significantly increased compared to that of CD142-negative cells. Moreover, CD142 overexpression promoted the invasion and migration of SGC083 cells, but CD142 silencing had the opposite effect. In addition, there was a positive correlation between CD142 expression in cancer tissues and serum Interleukin-8 (IL-8) levels. CD142 overexpression promoted IL-8 production in SGC083 cells. In vivo analysis showed that the implantation of CD142-positive SNU16 cells promoted the growth of xenograft tumor and the production of IL-8. Mechanistically, CD142 silencing not only inhibited the expression of

For a deep understanding of arsenic's mutagenicity, carcinogenicity and teratogenicity, the elucidation of arsenic binding proteins in organisms is a necessary prerequisite. Herein, a biotinylated phenylarsenite (Bio-PAO(III)) probe was synthesized for in situ binding to arsenic binding proteins in HepG2 cells. The Bio-PAO(III)-arsenic binding proteins complexes were captured by the prepared streptavidin-magnetic beads (SA-MBs) by specific interaction of biotin-SA. After magnetic separation, the arsenic binding proteins in the eluent was separated by sodium dodecyl sulfate-polyacrylamide - gel electrophoresis, and the in-gel tryptic digested protein bands were subjected to capillary high performance liquid chromatography coupled with electrospray ionization mass spectrometry analysis. 32 kinds of arsenic binding proteins were identified in HepG2 cells, which could be divided into three groups, structure proteins, enzymes related with tricarboxylic acid cycle and fatty synthesis and transcriptional regulator. Poly [ADP-ribose] polymerase 1 and general transcription factor IIH subunit 1 were identified to bind with arsenicals, which may affect the process of nucleotide excision repair in HepG2 cells.

Cellular uptake of Au NPs is the premise for their application in drug delivery, cell/tissue imaging and quantitation analysis of biomarkers in the cells. However, conventional methods for cell analysis may lead to the loss of important information from abnormal or atypical cells in the cell population. In this work, with 15, 30 and 60 nm Au NPs@citric acid and Au NPs@DNA as model materials, the cellular uptake of Au NPs in single HeLa cells is studied by using an on-line droplet chip inductively coupled plasma mass spectrometry hyphenated technique. It is found that the average amount of Au uptake for Au NPs@citric acid is higher than that for Au NPs@DNA at high incubation concentrations. The distribution of the number of uptaken Au NPs in single HeLa cells shows a great difference when HeLa cells are incubated with different Au NPs. The percentage of cells uptaking Au NPs in the cell population also reveals a difference in cellular uptake between Au NPs@citric acid and Au NPs@DNA at the single-cell level. To explain the abovementioned phenomenon, the endocytosis mechanisms of Au NPs are investigated. Clathrin-mediated endocytosis is found to be the major internalization pathway for 15 and 30 nm Au NPs@DNA.

Therapeutic drug monitoring is central to optimize therapeutic efficacy and minimize adverse events; however, the pharmacokinetics and pharmacodynamics of most drugs differ greatly among individuals. Evaluation of the therapeutic response is in urgent need to help clinician predict the clinical dose of drug. Herein, we described an analytical assay using gold nanocluster (AuNC)-decorated metal-organic frameworks (MOFs) for targeted drug delivery and monitoring pharmacodynamics, giving attractive options for studying individualized therapy. The camptothecin (Cam) anticancer drug was caged in the NH

Zinc oxide (ZnO) nanoparticles (NPs) are widely used in daily life. However, common utilization of ZnO NPs results in increases in environmental release, and their health hazards have attracted extensive attention. To investigate the cytotoxicity of ZnO NPs and their mechanism in HepG2 cells, a comprehensive analytical system was developed. The internalization, cytotoxic mechanism, death mechanism and elimination behavior of three sizes of ZnO NPs were studied by electrothermal vaporization (ETV)-inductively coupled plasma mass spectrometry (ICP-MS), MTT assays, GSH measurements, ROS measurements and analyses of apoptosis and gene expression. The size-, dose- and time-dependent characteristics of ZnO NPs were determined, and the metabolism of ZnO NPs in cells was discussed. The cytotoxicity of ZnO NPs was confirmed to depend on both the size and concentration and was attributed to the release of Zn2+, induction of oxidative stress and inflammatory response; the death mode of HepG2 cells incubated with ZnO NPs was necrotic rather than programmed cell death.

As is well-known, arsenite (As(iii)) is a human carcinogen associated with many human cancers. As(iii) can act as a co-carcinogen to induce DNA damage with other carcinogens. Benzo(a)pyrene diol epoxide (BPDE) is one of the most-studied environmental carcinogens, which exists ubiquitously in our daily life. The elucidation of the mechanism of As(iii) as a co-carcinogen with BDPE in cells causing genotoxicity is beneficial for the evaluation of its bioeffect. In this study, a comprehensive analytical system is used for DNA damage evaluation, BPDE-DNA adduct detection, arsenic speciation and gene expression analysis. Based on the experimental results, it can be inferred that BPDE and As(iii) synergistically cause genotoxicity, and the possible mechanism is that BPDE inhibits arsenic methylation, leading to cellular As(iii) enrichment. As(iii) inhibits nucleotide excision repair (NER) of the DNA adduct damage caused by BPDE. The synergistic effect of BPDE and As(iii) causes DNA strand break damage, which further results in carcinogenesis.

To determine the electroclinical features of fixation-off sensitivity (FOS) in patients with idiopathic generalized epilepsy (IGE). We searched the EEG database using the terms "fixation-off sensitivity" and "idiopathic generalized epilepsy" over a four-year period from March 2014 to April 2018 in the Xijing Hospital, Xi'an, China. FOS was evaluated according to the technique proposed by Panayiotopoulos. Photic stimulation procedure and neuropsychological testing were performed during video-EEG monitoring. FOS was observed in eight patients with several different IGE syndromes, including four with eyelid myoclonia/Jeavons syndrome, two with juvenile myoclonic epilepsy, one with photosensitivity epilepsy, and one with epilepsy with generalized tonic-clonic seizures only. FOS was associated with seizures in five patients manifesting with eyelid myoclonic, myoclonic, and myoclonic-tonic-clonic seizures, and eyelid myoclonic status. FOS coexisted with photosensitivity in six patients as independent EEG features. Neuropsychological testing revealed transitory cognitive impairments associated with FOS. FOS is associated with several different IGE syndromes and may coexist with photosensitivity in the same patient as independent EEG features. FOS may be associated with both clinical seizures and cognitive impairments. Intermittent photic stimulation and registration of different eye conditions with and without fixation will aid the study of the dynamics of the visual system in epilepsy patients. [Published with video sequences on www.epilepticdisorders.com].

Introduction The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer (BTC). Methods Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy (with capecitabine, S-1, oxaliplatin, irinotecan or PD-1 inhibitor), including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. Six patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95%CI = 1.8–6.8) and 6.2 months (95% CI = 4.6–7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1–2 in severity, apatinib treatment was well tolerated. Conclusions Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.

Significance Beclin 1, an essential autophagy protein, is important for tumor suppression in mice, as well as in human breast and ovarian cancers. However, it is not well understood how Beclin 1 acts as a tumor suppressor. By performing a genetic screen to identify genes whose loss blocks the ability of Beclin 1 to inhibit the growth of breast cancer cells and follow-up biological analyses, we have identified a mechanism by which Beclin 1 prevents breast cancer growth. We found that Beclin 1 promotes the plasma membrane localization of E-cadherin, a breast tumor-suppressor molecule that restricts tumor growth and metastases only when present at the cell surface. These findings have important implications for understanding the cell biology of human breast cancer., Beclin 1, an autophagy and haploinsufficient tumor-suppressor protein, is frequently monoallelically deleted in breast and ovarian cancers. However, the precise mechanisms by which Beclin 1 inhibits tumor growth remain largely unknown. To address this question, we performed a genome-wide CRISPR/Cas9 screen in MCF7 breast cancer cells to identify genes whose loss of function reverse Beclin 1-dependent inhibition of cellular proliferation. Small guide RNAs targeting CDH1 and CTNNA1, tumor-suppressor genes that encode cadherin/catenin complex members E-cadherin and alpha-catenin, respectively, were highly enriched in the screen. CRISPR/Cas9-mediated knockout of CDH1 or CTNNA1 reversed Beclin 1-dependent suppression of breast cancer cell proliferation and anchorage-independent growth. Moreover, deletion of CDH1 or CTNNA1 inhibited the tumor-suppressor effects of Beclin 1 in breast cancer xenografts. Enforced Beclin 1 expression in MCF7 cells and tumor xenografts increased cell surface localization of E-cadherin and decreased expression of mesenchymal markers and beta-catenin/Wnt target genes. Furthermore, CRISPR/Cas9-mediated knockout of BECN1 and the autophagy class III phosphatidylinositol kinase complex 2 (PI3KC3-C2) gene, UVRAG, but not PI3KC3-C1–specific ATG14 or other autophagy genes ATG13, ATG5, or ATG7, resulted in decreased E-cadherin plasma membrane and increased cytoplasmic E-cadherin localization. Taken together, these data reveal previously unrecognized cooperation between Beclin 1 and E-cadherin–mediated tumor suppression in breast cancer cells.

To explore the effects of microRNA (miR)-27b-3p-mediated homeobox A10 (HOXA10) on the proliferation, migration, and invasion of endometriosis cells (hEM15A).First, quantitative polymerase chain reaction (qPCR) was performed for the measurement of miR-27b-3p and HOXA10 expression in hEM15A cells and human embryonic stem cells (hESC). Then, the targeted relationship of miR-27b-3p with HOXA10 was verified by conducting a dual-luciferase reporter experiment. Subsequently, qPCR and western blot were performed to determine the effect of miR-27b-3p on HOXA10 expression. Finally, Cell Counting Kit-8, Transwell, and scratch assays were employed to determine the effects of miR-27b-3p and HOXA10 on the proliferative, migratory, and invasive abilities of hEM15A cells.In hEM15A cells, miR-27b-3p expression was increased and showed a negative correlation with the expression of HOXA10 (P0.05). The dual-luciferase reporter experiment confirmed that miR-27b-3p targeted the HOXA10 gene. Furthermore, qPCR and western blotting showed that miR-27b-3p regulated the expression of HOXA10. The proliferation, migration, and invasion abilities of hEM15A cells was significantly inhibited by suppressing miR-27b-3p expression or overexpressing HOXA10 (P0.05). Meanwhile, concurrent overexpression of miR-27b-3p and HOXA10 did not affect hEM15A cell activity (P0.05).Upregulation of miR-27b-3p can suppress HOXA10 expression, resulting in the enhancement of hEM15A cell proliferation, migration, and invasion.

This study aims to explore the application of blockchain technology in smart healthcare, establish a hierarchical theoretical framework of smart healthcare, reveal the impact of blockchain on smart healthcare, and finally, construct a development application system of smart healthcare under the blockchain based on stakeholder theory. However, such a hierarchical theoretical framework should consider not only the necessary attributes and the interrelationship among various aspects and attributes but also the role of multiple stakeholders. Therefore, the paper uses fuzzy set theory to filter unnecessary attributes, proposes a decision-making and experimental evaluation laboratory (DEMATEL) to manage the complex interrelationships between various aspects and attributes, and uses Interpretive Structure Modeling (ISM) to divide the hierarchy and construct a hierarchical theoretical framework. The results show that (1) the top-level design, the medical record management, and the doctor management are the root causes of system. (2) The specific application of blockchain in the field of smart healthcare is mainly carried out around the intelligent contract, which relies on the medical record management and is constrained by the system, and optimization of application is the key to system upgrading. (3) The internal and external regulation, the medical insurance, and the environmental governance play a guaranteed role for the development of the system and effectively safeguard the interests of stakeholders. (4) The application system of smart healthcare under the blockchain needs to be built based on three layers: the transaction layer, information layer, and stakeholder layer. The theoretical hierarchical framework is intended to guide smart healthcare towards blockchain applications, and stakeholders are suggested to participate in the development application systems.

Background: Chronic kidney disease (CKD) as a disease that poses a great threat to human health, which has become a public health issue of great concern. Studies have found that exercise training has a positive effect on improving the condition of chronic kidney disease. We will conduct a network meta-analysis to assess the effects of aerobic training, resistance training and combined aerobic and resistance training in treating CKD patients. Methods: We will search PubMed, EMBASE, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science to identify randomized control trails (RCTs) that assessed the effect of different exercise training for CKD patients. Cochrane Handbook will be used to evaluate the risk of bias of included articles. We will use Stata or R software to perform data analysis. Results and Conclusion: Our systematic review and network meta-analysis will be the first study that investigates the effect of different exercise training for CKD patients, and will provide evidence for management of chronic kidney disease. Ethics and dissemination: The data involved in this study are from published articles. For this reason, there is no need for ethical approval or patient consent. Trial registration: the registration number was: CRD42020157280

Study Objective To demonstrate stepwise techniques for the successful use of the laparoendoscopic single-site surgery (LESS) technique for safely performing pectopexy. Design Stepwise demonstration with narrated video footage (Canadian Task Force classification III). Setting An academic tertiary care hospital. Interventions Patient was a 48-year-old, gravida 2 para 2, having had 2 normal spontaneous vaginal deliveries, with stage III anterior vaginal prolapse and stage III uterine prolapse and posterior vaginal prolapse. The preoperative vaginal length was 6 cm. Laparoscopic sacrocolpopexy is the current gold standard for pelvic organ prolapse demonstrating a low recurrence rate; however, it can be technically challenging to perform, particularly in women with obesity or in the event of an anatomic variation. The pectineal ligament, also known as Cooper's ligament, is familiar to surgeons and can be used for a tension-free mesh suspension in patients with prolapse. Integration of LESS and pectopexy is a novel alternative, minimally invasive approach that is more cosmetic, simpler, and effective. The key steps in LESS pectopexy include the following: • LESS total laparoscopic hysterectomy with bilateral salpingectomy. • Anterior and posterior vaginal cuff dissection. • Exposure of the iliopectineal ligament (Cooper's ligament). • Tension-free mesh anchoring. • Reperitonealization. Measurements and Main Results The procedure was performed successfully in approximately 80 minutes with a postoperative vaginal length of 6 cm. Postoperative pelvic organ prolapse quantification was stage 0. Conclusion LESS is a feasible technique for pectopexy in patients with pelvic organ prolapse. A LESS pectopexy results in better cosmesis and offers an alternative for patients with challenging pelvic organ prolapse, such as those with obesity.

Time-resolved (TRA)-ICPMS has become a booming subfield of single-cell analysis tools in recent years, while generation of single cells remains the major challenge. Microfluidic devices reveal their great capability and potential in encapsulation of single cells into water droplets. However, current strategies to pinch off droplets require a specific oil phase, which is not compatible to conventional ICPMS and makes the signal of cells in the water phase susceptible. Herein, we built a 3D water-in-gas microfluidic device (3D W/G MFD) with commercially available components, producing single cell droplet enclosed by argon gas. By simply tuning the flow rate of gas and water, the droplets were generated to encapsulate single cells, which significantly reduced the probability of the single signal coming from multiple cells by 1 or 2 orders of magnitude compared to direct injection. The developed oil-free 3D W/G MFD was more friendly to online coupling with TRA-ICPMS than water-in-oil devices. The effect of Cd2+ on HepG2 cells was studied by single cell detecting total Zn with 3D W/G MFD-TRA-ICPMS, and the variation of labile Zn was explored by flow cytometry with an N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide probe. To the best of our knowledge, this work pioneered the exploration of variation in cellular metal content and speciation at the single-cell level, compensating for the deficiency of speciation analysis based on TRA-ICPMS and providing new insights into exploring the complexity of biology.

Fast green FCF (FGF) is often used in foods, pharmaceuticals, and cosmetics. However, little is known about the interactions of FGF with amyloid-β protein (Aβ) associated with Alzheimer's disease. In this study, the inhibitory effects of FGF on Aβ fibrillogenesis, the disruption of preformed Aβ fibrils, the reduction of Aβ-induced cytotoxicity, and the attenuation of Aβ-induced learning and memory impairments in mice were investigated. FGF significantly inhibited Aβ fibrillogenesis and disintegrated the mature fibrils as evidenced by thioflavin T fluorescence and atomic force microscopy studies. Co-incubation of Aβ with FGF greatly reduced Aβ-induced cytotoxicity in vitro. Moreover, FGF showed a protective effect against cognitive impairment in Aβ-treated mice. Molecular dynamics simulations further showed that FGF could synergistically interact with the Aβ17-42 pentamer via electrostatic interactions, hydrogen bonds and π-π interactions, which reduced the β-sheet content, and disordered random coils and bend structures of the Aβ17-42 pentamer. This study offers a comprehensive understanding of the inhibitory effects of FGF against Aβ neurotoxicity, which is critical for the search of effective food additives that can combat amyloid-associated disease.

Inductively coupled plasma mass spectrometry (ICP-MS) combined with element tags has been well designed and extensively applied in cell enumeration. It possesses superior quantitative capability, strong resistance to matrix interference, multiplex detection capability but destructive characteristic. Herein, we constructed an ICP-MS based multifunctional platform for capture, nondestructive enumeration, and release of circulating tumor cells (CTCs). Aptamer on capture probe recognized Mucin 1 (MUC1) on membrane of MCF-7 cells specifically, thus the cells were captured by probe and the Initiator originally hybridized with Aptamer was substituted by MUC1 and released into solution. Then the released Initiator was separated from the captured cells and hybridized with Tb labeled Substrate on detection probe to release a large amount of nicked Tb fragments through the nicking endonuclease assisted amplification for subsequent ICP-MS detection. Meanwhile, cells captured by probe were released by nuclease digestion for further reculture. Such a strategy effectively avoids CTCs destruction resulted from ICP-MS enumeration, increases the detection sensitivity of ICP-MS by involving nicking endonuclease assisted amplification, and realizes cell recovery for further analysis. A limit of detection of 87 MCF-7 cells and a linear range of 250-10 000 MCF-7 cells were realized for ICP-MS enumeration. A cell recovery of 52.7% (with capture and release efficiency of 63.9 and 82.5%, respectively) and a viability of 74.3% were obtained, meanwhile the released cells exhibited strong proliferation ability. This multifunctional platform for CTCs capture, enumeration, and release has great applicable potential in early diagnosis and individual treatment for cancer.

ZIF-8 nanoparticles (NPs) has been demonstrated with good potential in drug delivery, which causes an increasing attention on relevant toxicity study. In this work, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide), glutathione (GSH), reactive oxygen species (ROS), stain analysis and gene detection assays were performed on ZIF-8 (50, 90 and 200 nm) incubated HepG2 cells. Moreover, time-resolved inductively coupled plasma mass spectrometry (TRA-ICP-MS) was applied for single cell analysis; the variation in cellular zinc amount and the proportion of zinc up-taken cells was investigated as a function of NPs size, incubation concentration/time and elimination. Smaller size of ZIF-8 NPs would lead to higher zinc accumulation and toxicity. The function of ZIF-8 on cells is assumed to be mainly related to zinc intracellular accumulation. The possible action path is presented as high accumulation of zinc in ZIF-8 incubated cells lead to high ROS level and cellular inflammation, ultimately inducing necrocytosis. For better understanding of the bio-effect of ZIF-8, ZnO NPs and Zn2+ incubated HepG2 cells were evaluated in the same way. Higher accumulation of zinc in larger part of the cell population was found in ZIF-8 incubated cells than that in ZnO NPs incubated cells. It demonstrated higher bioavailability for ZIF-8 over ZnO NPs. While, in drug delivery application, the possible risk of the remained intracellular ZIF-8 cannot be ignored.

The growing use of rare-earth doped upconversion nanoparticles (UCNPs) has caused increasing concern about their biosafety. Here, to understand the toxicity of UCNPs and their mechanism in HepG2 cells, we systematically study the cytotoxicity, uptake and elimination behaviors of three types of UCNPs combined multiple cytotoxicity evaluation means with inductively coupled plasma mass spectrometry (ICP-MS) detection. Sodium yttrium fluoride, doped with 18% (molar ratio) ytterbium and 2% erbium (NaYF4: Yb3+, Er3+) was selected as the model UCNPs with two sizes (35 and 55 nm), and the poly(acrylic acid) and polyethylenimine were selected as the representatives of negative and positive surface coating of UCNPs, respectively. UCNPs were found to induce cytotoxicity in time- and dose-dependent manners, which might be mediated by reactive oxygen species generation and oxidative stress. Apoptosis, inflammation, and metabolic process were enhanced after cells exposed to 200 mg/L UCNPs for 48 h. Increase in the protein levels of cleaved caspased-9, cleaved caspase-3 and Bax and decrease in the anti-apoptotic protein, Bcl-2 suggested that the mitochondria mediated pathway was involved in UCNP-induced apoptosis. With the aid of ICP-MS, it demonstrated that the cytotoxicity was associated with internalized amount of UCNPs, which largely relied on their surface properties rather than size in the tested range. By comparing UCNPs with Y3+ ions, it demonstrated that NPs properties played a nonnegligible role in the cytotoxicity of UCNPs. These findings provide new insights for fundamental understanding of cytotoxicity of UCNPs and may contribute to more rational use of these materials in the future.

Long non‐coding RNAs (lncRNAs) have been illustrated to function as important regulators in carcinogenesis and cancer progression. However, the roles of lncRNA NNT‐AS1 in gastric cancer remain unclear. In the present study, we investigate the biological role of NNT‐AS1 in gastric cancer tumorigenesis. Results revealed that NNT‐AS1 expression level was significantly up‐regulated in GC tissue and cell lines compared with adjacent normal tissue and normal cell lines. The ectopic overexpression of NNT‐AS1 indicated the poor prognosis of GC patients. In vitro experiments validated that NNT‐AS1 knockdown suppressed the proliferation and invasion ability and induced the GC cell cycle progression arrest at G0/G1 phase. In vivo xenograft assay, NNT‐AS1 silencing decreased the tumour growth of GC cells. Bioinformatics online program predicted that miR‐424 targeted the 3′‐UTR of NNT‐AS1. Luciferase reporter assay, RNA‐immunoprecipitation (RIP) and RNA pull‐down assay validated the molecular binding within NNT‐AS1 and miR‐424, therefore jointly forming the RNA‐induced silencing complex (RISC). Moreover, E2F1 was verified to act as the target gene of NNT‐AS1/miR‐424, indicating the NNT‐AS1/miR‐424/E2F1 axis. In conclusion, our study indicates that NNT‐AS1 sponges miR‐424/E2F1 to facilitate GC tumorigenesis and cycle progress, revealing the oncogenic role of NNT‐AS1 for GC.

Loss of function of the DIS3L2 exoribonuclease is associated with Wilms tumor and the Perlman congenital overgrowth syndrome. LIN28, a Wilms tumor oncoprotein, triggers the DIS3L2-mediated degradation of the precursor of let-7, a microRNA that inhibits Wilms tumor development. These observations have led to speculation that DIS3L2-mediated tumor suppression is attributable to let-7 regulation. Here we examine new DIS3L2-deficient cell lines and mouse models, demonstrating that DIS3L2 loss has no effect on mature let-7 levels. Rather, analysis of Dis3l2-null nephron progenitor cells, a potential cell of origin of Wilms tumors, reveals up-regulation of Igf2, a growth-promoting gene strongly associated with Wilms tumorigenesis. These findings nominate a new potential mechanism underlying the pathology associated with DIS3L2 deficiency.

Development of multimodal detection technologies for accurate diagnosis of cancer at early stages is in great demand. In this work, we report a novel approach using an aptamer-based dual-functional probe for rapid, sensitive, and specific counting and visualization of MCF-7 cells by inductively coupled plasma–mass spectrometry (ICP-MS) and fluorescence imaging. The probe consists of a recognition unit of aptamer to catch cancer cells specifically, a fluorescent dye (FAM) moiety for fluorescence resonance energy transfer (FRET)-based “off-on” fluorescence imaging as well as gold nanoparticles (Au NPs) tag for both ICP-MS quantification and fluorescence quenching. Due to the signal amplification effect and low spectral interference of Au NPs in ICP-MS, an excellent linearity and sensitivity were achieved. Accordingly, a limit of detection of 81 MCF-7 cells and a relative standard deviation of 5.6% (800 cells, n = 7) were obtained. The dynamic linear range was 2 × 102 to 1.2 × 104 cells, and the recoveries i...

Background Radix Ginseng, one of the well-known medicinal herbs, has been used in the management of diabetes and its complications for more than 1000 years. Purpose The aim of this review is devoted to summarize the phytochemistry and pharmacokinetics of Ginseng, and provide evidence for the antidiabetic effects of Ginseng and its ingredients as well as the underlying mechanisms involved. Methods For the purpose of this review, the following databases were consulted: the PubMed Database ( https://pubmed.ncbi.nlm.nih.gov ), Chinese National Knowledge Infrastructure ( http://www.cnki.net ), National Science and Technology Library ( http://www.nstl.gov.cn/ ), Wanfang Data ( http://www.wanfangdata.com.cn/ ) and the Web of Science Database ( http://apps.webofknowledge.com/ ). Results Ginseng exhibits glucose-lowering effects in different diabetic animal models. In addition, Ginseng may prevent the development of diabetic complications, including liver, pancreas, adipose tissue, skeletal muscle, nephropathy, cardiomyopathy, retinopathy, atherosclerosis and others. The main ingredients of Ginseng include ginsenosides and polysaccharides. The underlying mechanisms whereby this herb exerts antidiabetic activities may be attributed to the regulation of multiple signaling pathways, including IRS1/PI3K/AKT, LKB1/AMPK/FoxO1, AGEs/RAGE, MAPK/ERK, NF-κB, PPARδ/STAT3, cAMP/PKA/CERB and HIF-1α/VEGF, etc. The pharmacokinetic profiles of ginsenosides provide valuable information on therapeutic efficacy of Ginseng in diabetes. Although Ginseng is well-tolerated, dietary consumption of this herb should follow the doctors’ advice. Conclusion Ginseng may offer an alternative strategy in protection against diabetes and its complications through the regulations of the multi-targets via various signaling pathways. Efforts to understand the underlying mechanisms with strictly-controlled animal models, combined with well-designed clinical trials and pharmacokinetic evaluation, will be important subjects of the further investigations and weigh in translational value of this herb in diabetes management.

In recent years, single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) has become a powerful tool for biological quantitative analysis. Homogeneous analysis method requires no separation and washing steps, which is suited for the analysis of highly infectious pathogens, so as to reduce the risk of infection during the operation. SARS-CoV-2 spreads all over the world, and its early infection symptoms are similar to influenza, which brings inconvenience to triage. Therefore, developing novel analytical method for simultaneous detection of multiple viral nucleic acids is essential. Taking the advantages of SP-ICP-MS and homogeneous analysis strategy, a SP-ICP-MS homogeneous nucleic acid assay by using gold nanoparticles (Au NPs) and silver nanoparticles (Ag NPs) probes was established for simultaneous sensitive analysis of SARS-CoV-2 and influenza A (H3N2). In the present of target SARS-CoV-2 or H3N2 nucleic acids, corresponding Au NPs or Ag NPs probes form larger aggregates, resulting in increased pulse signal intensity and reduced pulse signal frequency of the corresponding NPs in SP-ICP-MS measurement. In this assay, the reaction system of Au NPs and Ag NPs probes does not interfere with each other, and there was no separation and washing procedure, which facilitates operation, saves the analysis time, and improves the analysis efficiency. The linear range of this method is 5–1000 pmol L−1, with low-level limits of quantification of target nucleic acid. The developed SP-ICP-MS simultaneous homogeneous detection method has a good potential for detecting nucleic acid, protein, cell and other biological samples by changing different modification sequences on the NPs probes., Graphical abstract Image 1

Matrix metalloproteinase 2 (MMP2) plays an important role in tumor growth, invasion and metastasis. In this work, a dual-functional magnetic microsphere probe was designed for ICP-MS quantification and fluorescence imaging of MMP2 in cell secretion. In the designed probe, a NH2-peptide (-FAM)-biotin was used as a bridge for the combination of carboxylated magnetic beads (MBs-COOH) and streptavidin functionalized gold nanoparticle (Au NP-SA). Initially, the fluorescence of FAM was quenched by Au NP. Since the NH2-peptide (-FAM)-biotin had a MMP2-specifically recognized sequence, the peptide was specifically cleaved in the presence of MMP2, thus releasing Au NP for the ICP-MS quantification of MMP2 and turning on the fluorescence of FAM for the fluorescence imaging of MMP2. Under the optimal experimental conditions, a linear range of 0.05–50 ng mL−1 and a limit of detection of 0.02 ng mL−1 were obtained for MMP2. The relative standard deviation (n = 7, c = 0.1 ng mL−1) of the proposed method was 5.4%. With good sensitivity and good accuracy, the proposed method realized the quantification and imaging of MMP2 in A549 cell secretion. The proposed method was applied to monitor the expression of MMP2 in the A549 cell secretion under the stimulation of Cd2+, providing a new detection strategy in the study of MMP2-related life process.

Cinnamaldehyde, one of the active components derived from Cinnamon, has been used as a natural flavorant and fragrance agent in kitchen and industry. Emerging studies have been performed over the past decades to evaluate its beneficial role in management of diabetes and its complications. This review highlights recent advances of cinnamaldehyde in its glucolipid lowering effects, its pharmacokinetics, and its safety by consulting the Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, National Science and Technology Library, Wanfang Data, and the Web of Science Databases. For the inquiries, keywords such as Cinnamon, cinnamaldehyde, property, synthesis, diabetes, obesity, pharmacokinetics, and safety were used in various combinations. Accumulating evidence supports the notion that cinnamaldehyde exhibits glucolipid lowering effects in diabetic animals by increasing glucose uptake and improving insulin sensitivity in adipose and skeletal muscle tissues, improving glycogen synthesis in liver, restoring pancreatic islets dysfunction, slowing gastric emptying rates, and improving diabetic renal and brain disorders. Cinnamaldehyde exerts these effects through its action on multiple signaling pathways, including PPARs, AMPK, PI3K/IRS-1, RBP4-GLUT4, and ERK/JNK/p38MAPK, TRPA1-ghrelin and Nrf2 pathways. In addition, cinnamaldehyde seems to regulate the activities of PTP1B and α-amylase. Furthermore, cinnamaldehyde has the potential of metalizing into cinnamyl alcohol and methyl cinnamate and cinnamic acid in the body. Finally, there is a potential toxicity concern about this compound. In summary, cinnamaldehyde supplementation is shown to improve glucose and lipid homeostasis in diabetic animals, which may provide a new option for diabetic intervention. To this end, further scientific evidences are required from clinical trials on its glucose regulating effects and safety.

Trace heavy metals have great impact on biological system; therefore, it is essential to develop suitable analytical methods for the determination of trace heavy metals in biological samples to elucidate their biochemical and physiological functions in organisms. Herein, we presented a chip-based array monolithic microextraction system and combined it with inductively coupled plasma mass spectrometry (ICPMS) for online analysis of trace Hg, Pb, and Bi in real-world biological samples. Six ethylenediamine modified poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (poly(GMA-co-EDMA-NH2)) capillary monolithic columns were embedded parallelly in microchannels of a microfluidic chip for array monolithic microextraction. Various parameters affecting the chip-based array monolithic microextraction of target metals were investigated. The sample throughput of the proposed method was 16 h–1, with the limits of detection for Hg, Pb, and Bi of 23, 12, and 13 ng L–1, respectively. The developed method was ...

Single cell analysis is a significant research field in recent years reflecting the heterogeneity of cells in a biological system. In this work, a facile droplet chip was fabricated and online combined with time-resolved inductively coupled plasma mass spectrometry (ICPMS) via a microflow nebulizer for the determination of zinc in single HepG2 cells. On the focusing geometric designed PDMS microfluidic chip, the aqueous cell suspension was ejected and divided by hexanol to generate droplets. The droplets encapsulated single cells remain intact during the transportation into ICP for subsequent detection. Under the optimized conditions, the frequency of droplet generation is 3-6 × 106 min-1, and the injected cell number is 2500 min-1, which can ensure the single cell encapsulation. ZnO nanoparticles (NPs) were used for the quantification of zinc in single cells, and the accuracy was validated by conventional acid digestion-ICPMS method. The ZnO NPs incubated HepG2 cells were analyzed as model samples, and the results exhibit the heterogeneity of HepG2 cells in the uptake/adsorption of ZnO NPs. The developed online droplet-chip-ICPMS analysis system achieves stable single cell encapsulation and has high throughput for single cell analysis. It has the potential in monitoring the content as well as distribution of trace elements/NPs at the single cell level.

We report a sensitive, selective, simple, and reliable magnetic immunoassay protocol for detection and imaging of HepG2 cells. After being captured by Cs-doped multicore magnetic nanoparticles (MMNPs), HepG2 cells were labeled by CdSe/ZnS quantum dots (QDs), which could be visualized by fluorescence imaging using the photoluminescence property of QDs, and subsequently, they can be counted by inductively coupled plasma mass spectrometry (ICP-MS) with Cd/Cs as elemental tag. Because of the superior photoluminescence properties and the large quantities of detectable Cd atoms contained in the QDs core, QDs play a dual function role in this assay, making the method easier and more comprehensive than other similar approaches. Under the optimal conditions, the limit of detection of 61 HepG2 cells and the relative standard deviation of 5.4% (800 HepG2 cells, n = 7) were obtained. The linear range was 200-30 000 cells, and the recoveries in human whole blood were in the range of 86-104%. The proposed method enables us not only to count but also to see the cancer cells with the same labeling process, opening a promising avenue for research and clinical application.

Sensitive detection of circulating tumor cells (CTCs) is of great significance in the early detection of cancer and cancer metastasis. This work reported an efficient, specific, and sensitive immunoassay protocol for detection of tumor cells by using inductively coupled plasma mass spectrometry (ICP-MS) with gold nanoparticles (AuNPs) labeling and hybridization chain reaction (HCR) amplification. In the established approach, antibodies against epithelial cell adhesion molecule (anti-EpCAM) conjugated magnetic beads (MBs) were used for selective capture of tumor cells from peripheral blood, aptamer was applied for the recognition of captured tumor cells, and AuNPs labeled DNA concatamer was used as the signal probe for tumor cell labeling and ICP-MS detection. Due to the dual amplification effect of AuNPs and HCR, the limit of detection of this ICP-MS based method for HepG2 cells was as low as 15 cells, and the linear range was 40-8000 cells with the relative standard deviation for seven replicate detections of 200 HepG2 cells was 8.7%. Furthermore, the applicability of the method for the analysis of peripheral blood samples was demonstrated by the spiking tests. The established method was highly specific and sensitive for the detection of HepG2 cells, and has a good application potential in clinical diagnosis.

Purpose: Electronic portals provide patients with real-time access to personal health records. Use of this technology by individuals with cancer is particularly intensive. We therefore examined patterns of use of electronic portals by clinic staff at a National Cancer Institute–designated comprehensive cancer center. Methods: We identified and characterized cancer center providers and clinic staff who performed electronic activities related to MyChart, the institution’s personal health records portal, from 2009 to 2014. Total MyChart actions and messages received were quantified and characterized according to type, timing, and staff category. Results: Two hundred eighty-nine employees were included in our analysis: 85 nurses (29%), 79 ancillary staff (27%), 49 clerical/managerial staff (17%), 47 physicians (16%), and 29 advanced practice providers (10%). These individuals performed 740,613 MyChart actions and received 117,799 messages. Seventy-seven percent of actions were performed by nurses, 11% by ancillary staff, 6% by advanced practice providers, 5% by physicians, and 1% by clerical/managerial staff. From 2011 to 2014, staff MyChart activity increased approximately 10-fold. On average, 6.3 staff MyChart actions were performed per patient-initiated message. In 2014, nurses performed an average of 3,838 MyChart actions and received an average of 589 messages, compared with 591 actions and 87 messages in 2011 ( P < .001). Sixteen percent of all actions occurred outside clinic hours. Conclusion: Cancer center employee effort related to an electronic patient portal has increased markedly over time, particularly among nursing staff. Because further uptake of this technology is expected, it is critical to consider potential effects on clinical resources, employee and patient satisfaction, and patient safety.

Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5.

Background The present study aimed to evaluate the correlation of integrin alpha 7 (ITGA7) with patients' clinicopathological characteristics and survival profiles, as well as its influence on cell proliferation, apoptosis, and stemness in non–small‐cell lung cancer (NSCLC). Methods A total of 397 NSCLC patients underwent surgical resection were included, and ITGA7 was measured in tumor tissues and adjacent tissues by immunohistochemistry. patients' clinical data were extracted from database, and follow‐up records were reviewed. In cellular experiments, expression of ITGA7 was measured in NSCLC cell lines and normal human lung epithelial cell line by RT‐qPCR. The influence of ITGA7 on cell activity was assessed by transfecting overexpression plasmids and knockdown plasmids of ITGA7 into A549 cells. Results Integrin alpha 7 was upregulated in tumor tissues compared with the adjacent tissues of NSCLC patients. Patients with ITGA7 high expression presented poorer pathological differentiation, larger tumor size, and more advanced TNM stage compared with patients with ITGA7 low expression. For survival profiles, both disease‐free survival and overall survival were shorter in ITGA7 high expression patients compared with ITGA7 low expression patients. In cellular experiments, ITGA7 was upregulated in NCI‐H1650, A549, HCC‐827, and NCI‐H1299 cells compared with normal human lung epithelial cells BEAS‐2B. In addition, ITGA7 promoted cell proliferation, inhibited cell apoptosis, and facilitated cell stemness in A549 cells. Conclusion Integrin alpha 7 correlates with poor clinicopathological characteristics and survival profiles, and it promotes cell proliferation, stemness but suppresses cell apoptosis in NSCLC.

This review aimed to provide a general view of catalpol in protection against diabetes and diabetic complications, as well as its pharmacokinetics and safety concerns. The following databases were consulted with the retrieval of more than 100 publications through June 2019: PubMed, Chinese National Knowledge Infrastructure, WanFang Data, and web of science. Catalpol exerts an anti-diabetic effect in different animal models with an oral dosage ranging from 2.5 to 200 mg/kg in rats and 10 to 200 mg/kg in mice. Besides, catalpol may prevent the development of diabetic complications in kidney, heart, central nervous system, and bone. The underlying mechanism may be associated with an inhibition of inflammation, oxidative stress, and apoptosis through modulation of various cellular signaling, such as AMPK/PI3K/Akt, PPAR/ACC, JNK/NF-κB, and AGE/RAGE/NOX4 signaling pathways, as well as PKCγ and Cav-1 expression. The pharmacokinetic profile reveals that catalpol could pass the blood-brain barrier and has a potential to be orally administrated. Taken together, catalpol is a well-tolerated natural compound with promising pharmacological actions in protection against diabetes and diabetic complications via multi-targets, offering a novel scaffold for the development of anti-diabetic drug candidate. Further prospective and well-designed clinical trials will shed light on the potential of clinical usage of catalpol.

Phosphorylated p53 proteins are biomarkers with clinical utility for early diagnosis of cancer, but difficult to quantify. An inductively coupled plasma mass spectrometry (ICP-MS) based immunoassay is described here that uses uniform lanthanide nanoparticles (NPs) as elemental tags for the simultaneous determination of two phosphorylated p53 proteins. Apoferritin templated europium (Eu) phosphate (AFEP) NPs and apoferritin templated lutetium (Lu) phosphate (AFLP) NPs with 8 nm in diameter were used to label two phosphorylated p53 proteins at serine 15 and serine 392 sites (p-p5315 and p-p53392), respectively. The assay has a sandwich format, and p-p5315 and p-p53392 were first captured and then recognized by AFEP and AFLP NPs labelled antibodies, respectively. The Eu and Lu were then released from the immune complexes under acidic condition for ICP-MS measurement. The limits of detection for p-p5315 and p-p53392 are 200 and 20 pg·mL−1, with linear ranges of 0.5–20 and 0.05–20 ng·mL−1, respectively. The method was further applied to study the response of p-p5315 and p-p53392 in SCC-7 cells exposed to the natural carcinogen arsenite. A significant up-regulation of p-p5315 and p-p53392 can be observed when cells were exposed to arsenite at 5 μmol·L−1 level for 24 h.