CircSTRBP contributes to H2O2-induced lens epithelium cell dysfunction through increasing NOX4 mRNA stability by recruiting IGF2BP1.

Previous studies have shown that the development of age-related cataract (ARC) is involved in lens epithelium dysfunction, which is associated with abnormally expressed circular RNAs (circRNAs). The current work aims to probe the role of circSTRBP (hsa_circ_0088,427) in hydrogen peroxide (H2O2)-induced lens epitheliums. Lens epithelium tissues were harvested from ARC or normal subjects (n = 23). CircSTRBP, spermatid perinuclear RNA binding protein (STRBP), and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (NOX4) levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation, cycle progression, and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), and flow cytometry assays. Caspase 3 activity, reactive oxygen species (ROS), malondialdehyde (MDA), and Glutathione peroxidases (GSH-PX) levels were detected using corresponding kits. NOX4 protein level was determined using Western blot. The interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and circSTRBP or NOX4 was assessed through RNA immunoprecipitation (RIP). CircSTRBP and NOX4 abundances were increased in lens epithelium samples from ARC patients and H2O2-treated SRA01/04 cells. CircSTRBP knockdown might abolish H2O2-triggered SRA01/04 cell proliferation repression and apoptosis and oxidative stress promotion. In mechanism, circSTRBP is bound with IGF2BP1 and improves the stability and expression of NOX4 mRNA in SRA01/04 cells. CircSTRBP facilitated H2O2-induced SRA01/04 cell apoptosis and oxidative stress through by enhancing NOX4 mRNA stability via recruiting IGF2BP1, providing novel insights for ARC progression and treatment.

Characterization of a chlorine resistant and hydrophilic TiO2/calcium alginate hydrogel filtration membrane used for protein purification maintaining protein structure.

The development of membranes for protein purification has stringent requirement of disinfection resistance, low protein adsorption and anti-fouling, without changing protein structure. In this study, hydrophilic titanium dioxide (TiO2)/calcium alginate (TiO2/CaAlg) hydrogel membranes were prepared by a simple ionic cross-linking method. The effects of the porogenic agent polyethylene glycol (PEG) concentration, the molecular weight of PEG, and the concentration of TiO2 on the filtration properties were systematically investigated. The TiO2/CaAlg membrane exhibited excellent bovine serum albumin (BSA) rejection and anti-fouling properties. The mechanical properties and surface energy of the TiO2/CaAlg membrane were significantly improved. The chemical bonding mechanism of TiO2 and NaAlg was investigated by molecular dynamic simulation. The TiO2/CaAlg membrane had good chlorine resistance and could be disinfected or cleaned with sodium hypochlorite. The TiO2/CaAlg hydrogel membrane loaded with polyhydroxybutyrate (PHB) nanofibers maintained high flux (136.7 L/m2h) and high BSA rejection (98.0 %) at 0.1 MPa. The results of circular dichroism and synchronous fluorescence indicated that the secondary structure of BSA was maintained after membrane separation. This study provides one method for the preparation of green and environmentally friendly membrane for protein purification.

In-Situ Fabrication of Electroactive Cu2+-Trithiocyanate Complex and Its Application for Label-Free Electrochemical Aptasensing of Thrombin.

The preparation of an electroactive matrix for the immobilization of the bioprobe shows great promise to construct the label-free biosensors. Herein, the electroactive metal-organic coordination polymer has been in-situ prepared by pre-assembly of a layer of trithiocynate (TCY) on a gold electrode (AuE) through Au-S bond, followed by repetitive soaking in Cu(NO3)2 solution and TCY solutions. Then the gold nanoparticles (AuNPs) and the thiolated thrombin aptamers were successively assembled on the electrode surface, and thus the electrochemical electroactive aptasensing layer for thrombin was achieved. The preparation process of the biosensor was characterized by an atomic force microscope (AFM), attenuated total reflection-Fourier transform infrared (ATR-FTIR), and electrochemical methods. Electrochemical sensing assays showed that the formation of the aptamer-thrombin complex changed the microenvironment and the electro-conductivity of the electrode interface, causing the electrochemical signal suppression of the TCY-Cu2+ polymer. Additionally, the target thrombin can be label-free analyzed. Under optimal conditions, the aptasensor can detect thrombin in the concentration range from 1.0 fM to 1.0 µM, with a detection limit of 0.26 fM. The spiked recovery assay showed that the recovery of the thrombin in human serum samples was 97.2-103%, showing that the biosensor is feasible for biomolecule analysis in a complex sample.

Clinical value of contrast-enhanced ultrasonography in focal hypoechogenic lesions of thyroid.

OBJECTIVE: The objectives of this study were to analyze the accuracy of contrast-enhanced ultrasonography (CE-US) in diagnosing focal hypoechogenic lesions of the thyroid (FHLT), and to explore the clinical value of CE-US in the diagnosis of FHLT. METHODS: Patients undergoing CE-US and ultrasound-guided fine needle aspiration (US-FNA) of FHLT at First Hospital of China Medical University between January 2017 and December 2018 were selected for the study; this included patients with papillary thyroid carcinoma (PTC), subacute thyroiditis (SAT) and focal Hashimoto thyroiditis (FHT). All patients underwent color Doppler ultrasonography (CD-US) after which thyroid image reporting and data system (TI-RADS) grading were done. Then, each patient underwent CE-US and US-FNA. The results of the CE-US were analyzed using descriptive statistics. The cytopathological results from the US-FNAs were the gold standard used to confirm the diagnoses. RESULTS: A total of 56 patients were selected for the study. In the PTC group (n = 16), grading was as follows: TI-RADS4a, n = 3; TI-RADS4b, n = 12; and TI-RADS4c, n = 1. More patients with PTC showed heterogeneous hypoenhancement (n = 15) than heterogeneous isoenhancement (n = 1) on CE-US. In the SAT group (n = 24), grading was as follows: TI-RADS3, n = 1; TI-RADS4a, n = 18; TI-RADS4b, n = 5. Fewer patients with SAT showed heterogeneous hypoenhancement (n = 2) than heterogeneous isoenhancement (n = 22) on CE-US. In the FHT group (n = 16), grading was as follows: TI-RADS3, n = 1; TI-RADS4a, n = 11; TI-RADS4b, n = 4. Of those in the FHT group, one patient showed heterogeneous isoenhancement, one patient showed heterogeneous hypoenhancement, and 14 showed uniform isoenhancement on CE-US. The diagnostic accuracy of CD-US alone differed significantly from that of CD-US + CE-US (p < 0.05). CONCLUSION: CE-US has a high diagnostic accuracy for FHLT and can be used to identify PTC, SAT, and FHT.

Non-invasive SERS serum detection technology combined with multivariate statistical algorithm for simultaneous screening of cervical cancer and breast cancer.

Surface-enhanced Raman scattering (SERS), as a rapid, reliable and non-destructive spectral detection technology, has made a series of breakthrough achievements in screening and pre-diagnosis of various cancerous tumors. In this paper, high-performance gold nanoparticles/785 porous silicon photonic crystals (Au NPs/785 PSi PhCs) active SERS substrates were specially designed for serum testing, and realized highly sensitive detection of serum from healthy people, patients with cervical cancer and breast cancer. Based on the SERS spectra of the three groups of serum, the significant differences between the healthy group and cancer group at 1030 cm-1 and 1051 cm-1 were analyzed, and the similar but different serum SERS spectra of cervical cancer and breast cancer patients were compared. In addition, the spectral difference detected by SERS technology combined with a multivariate statistical algorithm was used to distinguish three kinds of serum. The serum SERS spectral sensitive bands were extracted by recursive weighted partial least squares (rPLS), and the three classification diagnosis models were established by combining orthogonal partial least squares discriminant analysis (OPLS-DA), linear discriminant analysis (LDA) and principal component analysis support vector machine (PCA-SVM) for synchronous classification and discrimination of the three groups of serum. The diagnostic results showed that the overall screening accuracy of three models were 93.28%, 97.77% and 94.78%, respectively. These above results confirmed that the Au NPs/785 PSi PhCs can realize super-sensitive detection of serum, and the established diagnostic model has great potential for pre-diagnosis and simultaneous screening of cervical cancer and breast cancer.

Establishment of a reliable scheme for obtaining highly stable SERS signal of biological serum.

As a rapid and non-destructive biological serum detection method, SERS technology was widely used in the screening and medical diagnosis of various diseases by combining the analysis of serum SERS spectrum and multivariate statistical algorithm. Because of the high complexity of serum components and the variability of SERS spectra, which often resulted in the phenomenon that the SERS spectrum of the same biological serum was significantly different due to the different test conditions. In this experiment, through the dilution treatment of the serum and the systematic test of the serum of all concentration gradients with lasers of wavelength of 785, 633 and 532 nm, the most suitable conditions for detecting the serum were investigated. The experimental results showed that only when the serum is diluted to low concentration (10 ppm), the SERS spectrum with high reproducibility and stability could be obtained, furthermore, the low concentration serum had weak tolerance to laser, and 532 nm laser was not suitable for serum detection. In this paper, a set of test scheme for obtaining highly stable serum SERS spectra was established by using high-performance gold nanoparticles (Au NPs) as the active substrate of SERS. Through comparative analysis of SERS spectrum of serum of normal people and cervical cancer, the reliability of the established low-concentration serum test program was verified, as well as its great potential advantages in disease screening and diagnosis.

Associations of BRAF V600E, clinical pathology and imaging factors with the recurrence rate of papillary thyroid microcarcinoma.

In the present study, the recurrence rate of papillary thyroid microcarcinoma (PTMC) was assessed by analyzing postoperative follow-up data of affected patients and its associations with BRAF V600E, clinical pathology and imaging factors were explored. A total of 506 patients with PTMC were selected who underwent surgery from January 2014 to March 2016. The maximal diameter of thyroid nodules was ≤1 cm and all patients who underwent BRAF V600E testing and evaluation for lymph node metastasis. Postoperatively, each patient was regularly followed up to detect recurrence. Categorical variables were comparatively analyzed using univariate Cox linear regression analysis to screen for protective and adverse factors influencing recurrence of PTMC. A stepwise Cox proportional hazards regression model analysis was performed to explore risk factors affecting recurrence. Among the 506 patients, 477 were followed up, 29 were lost to follow-up and 26 patients experienced recurrence. The 5-year recurrent rate of PTMC was 5.45%. The univariate Cox regression analysis indicated that PTMC recurrence was influenced by BRAF V600E, sex, multifocality, capsular invasion and lateral cervical lymph node metastasis (P<0.05), but not by age, tumor location on the thyroid, size, single central lymph node metastasis, distant metastasis and operative approach (P>0.05). The significant factors associated with recurrent PTMC were subjected to stepwise multivariate Cox proportional hazards regression model analysis and the results indicated that BRAF V600E, sex, multifocality and lateral cervical lymph node metastasis were independent factors influencing recurrence in patients with PTMC, with a statistically significant difference (P<0.05). In conclusion, BRAF V600E, sex, multifocality and lateral cervical lymph node metastasis are independent risk factors for recurrent PTMC.

Synthetic MUC1 breast cancer vaccine containing a Toll-like receptor 7 agonist exerts antitumor effects.

Adjuvant immunotherapy has recently emerged as a potential treatment strategy for breast cancer. The tumor-associated protein mucin 1 (MUC1) has received increasing attention due to its high expression in numerous types of common tumors, in which MUC1 acts as a cancer antigen. However, the simple mixed composition of an adjuvant and a peptide is not a sufficient rationale for a MUC1 peptide-based vaccine. The present study developed a novel Toll-like receptor 7 (TLR7) agonist-conjugated MUC1 peptide vaccine (T7-MUC1), which elicited an effective immune response and a robust antitumor effect in a mouse breast cancer model. In vitro, T7-MUC1 significantly increased the release of cytokines in mouse bone marrow dendritic cells and spleen lymphocytes, and induced the dendritic cell-cytokine-induced killer response against tumor cells with high MUC1 expression. In vivo, it was observed that the 4T1 tumor weights in mice immunized with the T7-MUC1 conjugate were reduced by ≥70% compared with those in the control group. Furthermore, the therapeutic responses in vivo were attributed to the increase in specific humoral and cellular immunity, including high antibody titers, antibody-dependent cell-mediated cytotoxicity and cytotoxic T-lymphocyte activity. The percentages of CD3+/CD8+ T-cells were significantly higher in the T7-MUC1 treatment group compared with those in the control group. Therefore, the results of the present study suggested that the T7-MUC1 vaccine inhibited tumor growth in mice and thus may have potential as a therapeutic candidate in clinical trials for breast cancer immunotherapy.

An APETALA2/ethylene responsive factor, OsEBP89 knockout enhances adaptation to direct-seeding on wet land and tolerance to drought stress in rice.

Water stress is the most important adverse factor limiting rice production. Too much water leads to flood and too little leads to drought. Floods and droughts can severely damage crop at different times of the rice life cycle. So the research on submergence tolerance and drought resistance of rice is particularly urgent. In this study, we reported that OsEBP89 (Oryza sativa Ethylene-responsive element binding protein, clone 89), a member of the AP2/ERF subfamily, is involved in a novel signal transduction associated with the tolerance to drought and submergence stress. OsEBP89 was found to be strongly inhibited by drought stress and promoted by submergence. The OsEBP89 protein was located at the nucleus in the rice protoplast. Loss of OsEBP89 was found to improve the seed germination under submerged conditions and also enhanced the tolerance to drought stress throughout growth stage. Additionally, OsEBP89 knockout rice plants increased the accumulation of proline, improved the ability to scavenge ROS compared to overexpression lines and wild type after PEG treatment. Transcriptome data indicates that knockout of OsEBP89 improved the expression of specific genes in response to adverse factors, such as OsAPX1, OsHsfA3, and OsP5CS. Further results indicate that OsEBP89 can interact with and be phosphorylated by SnRK1α (sucrose non-fermenting-1-related protein kinase-1 gene). These findings provide insight into the mechanism of abiotic stress tolerance, and suggest OsEBP89 as a new genetic engineering resource to improve abiotic stress tolerance in rice.

Microwave method synthesis of magnetic ionic liquid/gold nanoparticles as ultrasensitive SERS substrates for trace clopidol detection.

Clopidol is one of the most widely used anti-coccidiosis drugs. Its residues in poultry products and the environment pose a serious threat to human health. In this work, microwave-assisted synthesis of magnetic ionic liquid/gold nanoparticles (MIL-Au NPs) as the SERS substrates were first designed for sensitive and reliable determination of clopidol residue in egg samples. The experiment shows that MIL(1-methyl-3-hexyl imidazole ferric tetrachloride ([C6mim]FeCl4)) and microwave play a key role in the dispersion and morphology of Au NPs. Under the optimal conditions, the as-prepared MIL-Au NPs were applied to the SERS detection of clopidol in methanol and egg solution and its detection limits can be as low as to 0.5 µg/kg (equal to 0.5 ppb) in both solutions. The standard curves with regression coefficients of 0.9298 and 0.93496 were constructed in the linear range of 100-1000 ppb and 0.5-50 ppb for clopidol in egg solutions. Moreover, satisfactory recoveries (97.5-103.2%) were obtained for egg samples. The developed SERS method provides a way for quantitation of clopidol and can be applied for the convenient, reliable, and highly sensitive detection of antibiotic residues in food and environment, which has great potential in food safety and biological monitoring. Graphical abstract.

Correlation between FAK and EGF-Induced EMT in Colorectal Cancer Cells.

Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of colorectal cancer, which is mediated by FAK and EGF. However, whether FAK participates in EMT in colorectal cancer cells through the EGF/EGFR signaling pathway remains unknown. The aim of this study was to investigate the effector mechanisms of FAK in the process of EGF-induced EMT in colorectal cancer cells and to determine whether miR-217 is involved in this process. Caco-2 cancer cells were routinely cultured with and without treatment with 100 ng/mL EGF, and changes in cell morphology were observed using an inverted microscope. In addition, a transwell assay was used to detect cell migration under the condition of EGF treatment. The expression of FAK, pFAK, E-cadherin, vimentin, and ß actin was assessed by western blotting, and the expression of miR-217 was assessed using real-time PCR. We found that EGF induced EMT in colorectal cancer cells and enhanced cell migration and invasion ability. Moreover, FAK was involved in the EGF-induced EMT of colorectal cancer cells. EGF upregulated the expression of E-cadherin in colorectal cancer cells by activating FAK, and miR-217 was found to participate in EGF-induced EMT in colorectal cancer cells. Our findings indicate that EGF induces EMT in colorectal cancer cells by activating FAK, and miR-217 is involved in the EGF/FAK/E-cadherin signaling pathway.

A novel rice grain size gene OsSNB was identified by genome-wide association study in natural population.

Increasing agricultural productivity is one of the most important goals of plant science research and imperative to meet the needs of a rapidly growing population. Rice (Oryza sativa L.) is one of the most important staple crops worldwide. Grain size is both a major determinant of grain yield in rice and a target trait for domestication and artificial breeding. Here, a genome-wide association study of grain length and grain width was performed using 996,722 SNP markers in 270 rice accessions. Five and four quantitative trait loci were identified for grain length and grain width, respectively. In particular, the novel grain size gene OsSNB was identified from qGW7, and further results showed that OsSNB negatively regulated grain size. Most notably, knockout mutant plants by CRISPR/Cas9 technology showed increased grain length, width, and weight, while overexpression of OsSNB yielded the opposite. Sequencing of this gene from the promoter to the 3'-untranslated region in 168 rice accessions from a wide geographic range identified eight haplotypes. Furthermore, Hap 3 has the highest grain width discovered in japonica subspecies. Compared to other haplotypes, Hap 3 has a 225 bp insertion in the promoter. Based on the difference between Hap 3 and other haplotypes, OsSNB_Indel2 was designed as a functional marker for the improvement of rice grain width. This could be directly used to assist selection toward an improvement of grain width. These findings suggest OsSNB as useful for further improvements in yield characteristics in most cultivars.

Suppressive effects of sunitinib on a TLR activation-induced cytokine storm.

The cytokine storm includes a clinically heterogeneous set of life-threatening conditions that are manifested by extremely elevated serum cytokine levels and related symptoms (e.g., septic shock) and is devilishly mediated by Toll-like receptor (TLR) agonists in most situations. A tyrosine kinase inhibitor (TKIs), sunitinib, was screened in our group previously and showed antagonistic activity for cytokine release in a TLR7 stimulation model. In this paper, we further studied its mechanisms on interesting phenomena. In vitro, nearly all of the eleven TKIs decreased the TNF-α levels induced by the TLR7 agonist, especially sunitinib. Furthermore, sunitinib displayed potent inhibition of the cytokine levels triggered by several types of TLR ligands, including TLR3, TLR4, TLR7/8 and TLR9, in mouse spleen lymphocytes, mouse BMDCs and human PBMCs. The in vivo results showed that sunitinib efficiently depressed the LPS-induced cytokine storm, i.e., rapid and intense production of TNF-α and IL-6. Sunitinib further increased the survival time and decreased damage to mice. As for the immunosuppressive mechanisms of sunitinib, at least the PDGFR-activated ERK and p38 pathways were critical, although we could not rule out the possibility of other pathways being involved. In conclusion, our study demonstrated the inhibitory actions of TKIs on the cytokine storm induced by TLR ligands, primarily through PDGFR pathways, which could be potentially used to reduce cytokine storms in septic shock.

Association between rs1800629 polymorphism in tumor necrosis factor-α gene and dilated cardiomyopathy susceptibility: Evidence from case-control studies.

OBJECTIVE: Several published studies have investigated the association between the -308G/A (rs1800629) polymorphism in the tumor necrosis factor-α (TNF-α) gene and the risk of dilated cardiomyopathy (DCM). However, the TNF-α gene polymorphism has a controversial role in the pathogenesis of DCM among different populations. In the present study, a meta-analysis was performed to resolve this inconsistency. METHODS: Potentially eligible papers reporting an association between the TNF-α rs1800629 polymorphism and DCM susceptibility were searched in 4 databases including PubMed, EMBASE, Chinese Biomedical Database (CBM), and the Cochrane Library up to April 1, 2018. The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Subgroup analysis based on the ethnicity, studies with or without ischemic and valvular DCM was conducted. Publication bias detection was conducted using Begg test. RESULTS: Nine papers detailing case-control studies were included, reporting a total of 1339 DCM cases and 1677 healthy controls. The meta-analysis results indicated that TNF-α rs1800629 was associated with increased DCM susceptibility in the populations studied under the heterozygous model (AG vs GG: OR = 1.91, 95% CI = 1.05-3.50, P = .035) and dominant model (AG + AA vs GG: OR = 1.87, 95% CI = 1.01-3.45, P = .046). In the subgroup analysis for ethnicity, rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians under the 5 models (A vs G: OR = 2.87, 95% CI = 1.56-5.30, P = .001; AA vs GG: OR = 3.95, 95% CI = 1.13-13.82, P = 0.031; AG vs GG: OR = 3.8, 95% CI = 1.57-9.19, P = .003; AA vs GG + AG: OR = 2.51, 95% CI = 1.41-4.49, P = .002; AG + AA vs GG: OR = 3.77, 95% CI = 1.54-9.20, P = .004). CONCLUSION: There may be a moderate association between TNF-α rs1800629 polymorphism and DCM susceptibility in the whole populations studied; however, TNF-α rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians, which indicates that such associations may be different between ethnicities.

Corneal integrity and thickness of central fovea after phacoemulsification surgery in diabetic and nondiabetic cataract patients.

INTRODUCTION: Here we intended to investigate the changes in corneal endothelial cells and foveal thickness after phacoemulsification surgery on the eyes of diabetic and non-diabetic cataract patients. MATERIAL AND METHODS: A total of 120 cataract patients who were scheduled for phacoemulsification surgery and intraocular lens implantation were recruited and divided into 2 categories according to the diagnosis of diabetes mellitus. Changes in integrity, endothelial cell density (ECD), coefficient of variation (CV), percentage of hexagonal cells (PHC), central corneal thickness (CCT), and central foveal thickness (CFT) were all recorded at preoperative day 1 and postoperative day 3, 1 week, 1 month, 3 months and 6 months. RESULTS: None of the recorded variables showed any difference between the nondiabetic and diabetic groups before surgery (p > 0.05). During the postoperative 6 months, ECD and PHC decreased and CV increased in both groups (all ptime < 0.05), whereas CCT and CFT fluctuated in both groups significantly (both ptime < 0.05), with their individual peaks at postoperative 1 week in the diabetic group. The groups differed significantly in ECD, PHC, and CV at each time point postoperatively (all pgroup < 0.05). Furthermore, the diabetic group had improved CFT during the postoperative 1 month and higher CCT during the 6 months postoperatively than the nondiabetic group (all pgroup < 0.05). The time and group interactions were significant for ECD, CV, PHC, CCT and CFT (all pgroup × time < 0.05). CONCLUSIONS: The diabetic group had more changes in corneal endothelial cells and foveal thickness than the nondiabetic group postoperatively.

Gastric cancer vaccines synthesized using a TLR7 agonist and their synergistic antitumor effects with 5-fluorouracil.

BACKGROUND: Vaccines play increasingly important roles in cancer treatment due to their advantages of effective targeting and few side effects. Our laboratory has attempted to construct vaccines by conjugating TLR7 agonists with tumor-associated antigens. Furthermore, immunochemotherapy has recently become an appealing approach to cancer therapy. 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent, can reportedly potently and selectively kill tumor-associated MDSCs in vivo. METHODS: Gastric cancer vaccines were synthesized by the covalent attachment of our TLR7 agonist with the gastric cancer antigen MG7-Ag tetra-epitope, leading to T7 - ML (linear tetra-epitope) and T7 - MB (branched tetra-epitope). Cytokines induced by the vaccines in vitro were assessed by ELISA. A tumor challenge model was created by treating BALB/c mice on either a prophylactic or therapeutic vaccination schedule. 5-FU was simultaneously applied to mice in the combination treatment group. CTL and ADCC activities were determined by the LDH method, while CD3+/CD8+, CD3+/CD4+ T cells and MDSCs were evaluated by flow cytometry. RESULTS: In vitro, rapid TNF-α and IL-12 inductions occurred in BMDCs treated with the vaccines. In vivo, among all the vaccines tested, T7 - MB most effectively reduced EAC tumor burdens and induced CTLs, antibodies and ADCC activity in BALB/c mice. Immunization with T7 - MB in combination with 5-FU chemotherapy reduced tumor sizes and extended long-term survival rates, mainly by improving T cell responses, including CTLs, CD3+/CD8+ and CD3+/CD4+ T cells. 5-FU also enhanced the T7 - MB efficiency by reversing immunosuppressive factors, i.e., MDSCs, which could not be validly inhibited by the vaccines alone. In addition, T7 - MB repressed tumor growth and immune tolerance when the therapeutic schedule was used, although the effects were weaker than those achieved with either T7 - MB alone or in combination with 5-FU on the prophylactic schedule. CONCLUSIONS: A novel effective gastric cancer vaccine was constructed, and the importance of branched multiple antigen peptides and chemical conjugation to vaccine design were confirmed. The synergistic effects and mechanisms of T7 - MB and 5-FU were also established, observing mainly T cell activation and MDSC inhibition.

The anteroposterior diameter of nodules in the risk assessment of papillary thyroid microcarcinoma.

This study investigates the application of ultrasound, especially the anteroposterior diameter of nodules in the malignancy and metastasis risk assessment of papillary thyroid microcarcinoma through a retrospective analysis of 500 cases of thyroid nodule ultrasonography.We selected 500 patients with thyroid nodules (maximum nodule diameter ≤2.0 cm) that had been diagnosed clinically and graded TI-RADS 4c by ultrasonography and surgically treated. Among these, there were 258 cases of pathologically diagnosed papillary thyroid microcarcinoma, 72 cases of nodular goiter or adenoma, 137 cases of papillary thyroid carcinoma, 28 cases of acinar cell carcinoma, and 5 cases of undifferentiated carcinoma. In all cases, color Doppler ultrasonography had been performed preoperatively to determine the size and number of nodules, surrounding lymph node metastasis, and TI-RADS grading. Cases of papillary thyroid microcarcinoma diagnosed by pathology were selected as the study group, and cases of nodular goiter or adenoma as the control group. Each group was further subdivided based on the anteroposterior, vertical, and transverse nodule diameters. Intergroup statistical analysis was also performed. Receiver operating characteristic (ROC) curve analysis was conducted on the study and control groups based on the anteroposterior nodule diameters, and the optimal critical value for malignancy risk was determined. Thyroid nodules in the study group were divided into groups based on the presence or absence of lymph node metastasis. Based on the anteroposterior nodule diameter, ROC curve analysis was performed, and the optimal critical value for metastasis risk was determined.There were 500 cases of malignant nodules diagnosed by ultrasound. Among these, there were 428 cases of malignant nodules diagnosed by pathology. The coincidence rate of the ultrasound diagnosis with pathological diagnosis was 85.60%. While, interestingly, There was a significant statistical difference between the study and control groups based on the anteroposterior nodule diameter. When the anteroposterior nodule diameter was 0.7 cm, sensitivity of malignant diagnosis was 76.70% and specificity of that was 66.70%, and the Youden index was the highest. The lymph node metastasis rate for papillary thyroid microcarcinoma was 13.95%. Within this group, the lymph node metastasis rate for nodules ≥0.9 cm (anteroposterior diameter) was 38.46%. When the anteroposterior nodule diameter was equal to 0.9 cm, sensitivity of diagnosis was 83.30%, and specificity of that was 77.80%, and the Youden index was the highest.The anteroposterior diameter of thyroid nodules is more suitable for assessing their malignancy with 0.7 cm, which can be used as the critical value. Nodules ≥ 0.7 cm require surgical treatment, and those <0.7 cm can be observed. An anteroposterior diameter of 0.9 cm can be used as the critical value for assessing the metastasis risk of malignant thyroid nodules. During surgery, the dissection of central cervical lymph nodes is required for nodules ≥0.9 cm.

Clinical Application of Real-Time Shear Wave Elastography in Identifying the Histological Components of Parotid Adenolymphoma.

OBJECTIVE: This study aimed to investigate the relationship between the elastic modulus and the histological components of parotid adenolymphoma by using real-time shear wave elastography. METHODS: A total of 157 patients, histologically confirmed as having parotid adenolymphoma, were enrolled in the study. The maximum and the mean elastic modulus of the parotid mass were measured by using preoperative shear wave elastography. Parotid adenolymphoma was histopathologically subdivided into different types based on the relative proportion of stromal to cellular components. RESULTS: The maximal elasticity of parotid adenolymphoma ranged from 20.67 to 160.90 kPa, and the mean elasticity was 83.18 ± 39.15 kPa. The maximal elasticity of the 3 types of parotid adenolymphoma was 34.21 to 155.20, 20.67 to 104.20, and 45.89 to 160.90 kPa, respectively. The mean elasticity of the 3 types of parotid adenolymphoma was 89.16 ± 40.62, 63.24 ± 28.07, and 111.10 ± 37.85 kPa, respectively. The difference in the maximal elasticity among 3 groups was significant (P < 0.01). There was no significant difference in maximal elasticity of type II and type III as compared with type I adenolymphoma (P > 0.05). The maximal elasticity of type III adenolymphoma was significantly higher than that of type II (P < 0.05, t = 3.12). CONCLUSION: Shear wave elastography depicts parotid adenolymphoma with a variable appearance because of the relative proportions of stromal to cellular contents in the mass.

Combining thioridazine and loratadine for the treatment of gastrointestinal tumor.

In 2015, the American Society of Clinical Oncology announced that strategies of using combination therapies have been indicated to be effective against many types of cancer. In the present study, thioridazine (THZ) was used in a combination therapy with loratadine (LOR) to target gastrointestinal tumor, with the aim of investigating whether combined therapy was superior to monotherapy in its antitumor effects. The antiproliferative effects on CT26.WT and MFC cells were analyzed using cell-counting kit-8 assay, and synergistic effect was assessed by combination index (Fig. 1). Annexin V and propidium iodide staining indicated the combination therapy was able to induce apoptosis and that this may be mediated via caspase-3, -9 and poly (ADP-ribose) polymerase (PARP) (Fig. 2). Antitumor activity was also evaluated in CT26.WT xenografts in BALB/c mice (Fig. 3). Furthermore, as expected, combination therapy was able to successfully inhibit the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling pathway (Fig. 4). These findings suggest that the combination therapy with THZ and LOR may provide a promising therapy for gastrointestinal cancer.

Hydroxyapatite/chemically reduced graphene oxide composite: Environment-friendly synthesis and high-performance electrochemical sensing for hydrazine.

It is unexpectedly found that, the in-situ growth of hydroxyapatite (HAP) on graphene oxide (GO) under a moderate temperature (85°C) can effectively trigger the reduction of GO, which needs neither extra reducing agents nor high-temperature thermal treatment. The transmission electron microscope (TEM) experiment demonstrates that the rod-like HAP particles are well attached on the surface of reduced GO (rGO) to form the composite. Electrochemical sensing assays show that the synthesized HAP-rGO nanocomposite presents excellent electrocatalytic capacity for the oxidation of a toxic chemical of hydrazine. When the HAP-rGO modified electrode was utilized as an electrochemical sensor for hydrazine detection, outstanding performances in the indexes of low fabrication cost, short response time (~2s), wide linear range, low detection limit (0.43µM), and good selectivity were achieved. The developed sensor also shows satisfactory results for the detection of hydrazine in real industrial wastewater sample were achieved.