Diagnostic value of circulating tumor cells in patients with thyroid cancer: a retrospective study of 1478 patients.

BACKGROUND: Circulating tumor cell (CTC) detection is one form of liquid biopsy. It is a novel technique that is beginning to be applied in the field of thyroid cancer. The present study was designed to evaluate the diagnostic value of CTCs in patients with thyroid cancer. METHODS: A total of 1478 patients were retrospectively analyzed and divided into malignant group (n = 747) and benign group (n = 731). Peripheral blood was collected, and CTCs were enriched and quantified before surgery. The baseline data of the two groups were matched by Propensity Score Matching (PSM). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency of different indicators for thyroid cancer. The malignant group before PSM was further divided into subgroups according to the BRAF V600E mutation and lymphatic metastasis (N stage), and the number of CTCs in different subgroups was compared. RESULTS: After 1:1 PSM, baseline characteristics of the malignant group and benign group were matched and assigned 315 cases in each group. The number of CTCs and the TPOAb values were comparable in the two groups (p > 0.05). The TgAb values [1.890 (1.110 - 16.010) vs 1.645 (1.030 - 7.073) IU/mL, p = 0.049] were significantly higher in the malignant group than in the benign group. After PSM, ROC analyses showed that the areas under the curve (AUCs) of CTC, TgAb and ultrasound were 0.537 (sensitivity 65.6%, specificity 45.8%), 0.546 (sensitivity 40.0%, specificity 70.8%) and 0.705 (sensitivity 77.1%, specificity 63.2%), respectively. The AUCs of the combined detection of 'CTC + ultrasound' (combine 1) and the combined detection of 'CTC + TgAb + ultrasound' (combine 2) were 0.718 (sensitivity 79.3%, specificity 61.7%) and 0.724 (sensitivity 78.0%, specificity 63.3%), respectively. The AUC of ultrasound was significantly higher than CTC (p < 0.001). There was no statistically significant difference in AUC between combination 1 and ultrasound, and between combination 2 and ultrasound (p > 0.05). The number of CTCs between the N0 and N1 subgroups, and between the BRAF mutant and BRAF wild subgroups was comparable (p > 0.05). CONCLUSIONS: As an emerging and noninvasive testing tool, the efficacy of CTCs in diagnosing thyroid cancer is limited.

Genetic mapping of AhVt1, a novel genetic locus that confers the variegated testa color in cultivated peanut (Arachis hypogaea L.) and its utilization for marker-assisted selection.

Introduction: Peanut (Arachis hypogaea L.) is an important cash crop worldwide. Compared with the ordinary peanut with pure pink testa, peanut with variegated testa color has attractive appearance and a higher market value. In addition, the variegated testa represents a distinct regulation pattern of anthocyanin accumulation in integument cells. Methods: In order to identify the genetic locus underlying variegated testa color in peanut, two populations were constructed from the crosses between Fuhua 8 (pure-pink testa) and Wucai (red on white variegated testa), Quanhonghua 1 (pure-red testa) and Wucai, respectively. Genetic analysis and bulked sergeant analysis sequencing were applied to detect and identify the genetic locus for variegated testa color. Marker-assisted selection was used to develop new variegated testa peanut lines. Results: As a result, all the seeds harvested from the F1 individuals of both populations showed the variegated testa type with white trace. Genetic analysis revealed that the pigmentation of colored region in red on white variegated testa was controlled by a previous reported gene AhRt1, while the formation of white region (un-pigmented region) in variegated testa was controlled by another single genetic locus. This locus, named as AhVt1 (Arachis hypogaea Variegated Testa 1), was preliminary mapped on chromosome 08 through bulked sergeant analysis sequencing. Using a secondary mapping population derived from the cross between Fuhua 8 and Wucai, AhVt1 was further mapped to a 1.89-Mb genomic interval by linkage analysis, and several potential genes associated with the uneven distribution of anthocyanin, such as MADS-box, MYB, and Chalcone synthase-like protein, were harbored in the region. Moreover, the molecular markers closely linked to the AhVt1 were developed, and the new variegated testa peanut lines were obtained with the help of marker-assisted selection. Conclusion: Our findings will accelerate the breeding program for developing new peanut varieties with "colorful" testa colors and laid a foundation for map-based cloning of gene responsible for variegated testa.

Erratum: Influence of GLP-1 receptor agonist on insulin dosage and blood glucose control of patients with type 2 diabetes mellitus.

[This corrects the article on p. 11814 in vol. 13, PMID: 34786110.].

Mitofusin-2 Restrains Hepatic Stellate Cells' Proliferation via PI3K/Akt Signaling Pathway and Inhibits Liver Fibrosis in Rats.

The mitochondrial GTPase mitofusin-2 (MFN2) gene can suppress the cell cycle and regulate cell proliferation in a number of cell types. However, its function in hepatic fibrosis remains largely unexplored. We attempted to understand the mechanism of MFN2 in hepatic stellate cell (HSC) proliferation and the development of hepatic fibrosis. Rat HSC-T6 HSC were cultured and transfected by adenovirus- (Ad-) Mfn2 or its negative control (NC) vector (Ad-green fluorescent protein (GFP)); a rat liver cirrhosis model was established via subcutaneous injection with carbon tetrachloride (CCl4). Seventy-two rats were randomly divided into four groups: CCl4, Mfn2, GFP, and NC. Ad-Mfn2 or Ad-GFP was transfected into the circulation via intravenous injection at day 1, 14, 28, 42, or 56 after the first injection of CCl4 in the Mfn2/GFP groups. Biomarkers related to HSC proliferation and the development of hepatic fibrosis were detected using western blotting, hematoxylin-eosin and Masson staining, and immunohistochemistry. In vitro, Mfn2 interfered specifically with platelet-derived growth factor- (PDGF-) induced signaling pathway (phosphatidylinositol 3-kinase- (PI3K-) AKT), inhibiting HSC-T6 cell activation and proliferation. During the process of hepatic fibrosis in vivo, extracellular collagen deposition and the expression of fibrosis-related proteins increased progressively, while Mfn2 expression decreased gradually. Upregulating Mfn2 expression at the early stage of fibrosis impeded the process, triggered the downregulation of type I collagen, and antagonized the formation of factors associated with liver fibrosis. Mfn2 suppresses HSC proliferation and activation and exhibits antifibrotic potential in early-stage hepatic fibrosis. Therefore, it may represent a significant therapeutic target for eradicating hepatic fibrosis.

Autologous enzyme-linked immunosorbent facilitated antigen binding detects IgE-blocking activity based on direct competition between allergen-specific IgE and non-IgE.

Aim: To measure IgE-blocking activity induced by allergen immunotherapy (AIT) by an enzyme-linked immunosorbent facilitated antigen binding (ELIFAB) assay based on autologous immunoglobulin competition. Methods: The developed ELIFAB assay was used to investigate the kinetics of IgE-blocking activity in 87 patients at multiple AIT treatment time points, in comparison to the changes in IgG4. Results: High ELIFAB response was observed until 2.5 months of AIT, then significantly decreased after 4 months and remained suppressed during the 3-year AIT period. After treatment cessation, the ELIFAB response was maintained at the level seen at the 4-6 month treatment time point, similar to IgG4, indicating sustained IgE-blocking activity related to IgG4. Conclusion: This ELIFAB assay measures the IgE-blocking activity for autologous allergen-specific IgE and non-IgE during and after immunotherapy. It is suited for measuring the sustained IgE-blocking activity induced by AIT.

Lay abstract Allergy is a serious health problem worldwide. Allergen immunotherapy is a controlled exposure to allergen with the aim of modulating the immune response and reducing symptoms. The immune modulation includes a shift from the production of allergy-inducing IgE antibodies to inhibiting IgG antibodies and the competition between these antibodies for allergen binding when exposed to allergen may be central to the effect of the treatment. The current study addressed several ways of monitoring the changes in IgE and IgG antibodies during house dust mite immunotherapy. A novel assay for monitoring the competitive binding of these antibodies to house dust mite allergen is introduced; it may be used to monitor the immunological changes induced by immunotherapy and help increase treatment compliance.

Influence of GLP-1 receptor agonist on insulin dosage and blood glucose control of patients with type 2 diabetes mellitus.

OBJECTIVE: To determine the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) on cases with type 2 diabetes mellitus (T2DM) in terms of insulin dosage and blood glucose (BG) control. METHODS: A total of 180 patients with T2DM admitted to our hospital between March 2016 and March 2019 were selected and assigned to a GLP-1RA group (GLP-1 group, n=100) and a control group (control group, n=80). Patients in the GLP-1 group were treated with GLP-1RA combined with insulin, while those in the other group were treated with insulin alone. The following items of each patient were determined: Body weight, body mass index (BMI), waist circumference, blood pressure (BP), BG-related indexes, insulin dosage, insulin resistance index, cardiovascular function, serum lipid-related indexes, adverse reactions, total effective rate, and treatment satisfaction. RESULTS: Compared with the control group, the GLP-1 group showed a decrease in weight, BMI, waist circumference, BP, BG-related indexes, and insulin resistance index, consumed less insulin dosage, and also showed a decline in cardiovascular function, serum lipid-related indexes (total cholesterol (TC), triacylglycerol (TG), and low density lipoprotein cholesterol (LDL-C)), an increase in high density lipoprotein cholesterol (HDL-C), less adverse reactions, and higher total effective rate and treatment satisfaction. CONCLUSION: GLP-1RA contributes to better BG control of patients with T2DM, and it reduces the insulin dosage required during operation for its stimulation to the production of insulin.

The IgE Blocking Activity Induced by Dermatophagoides pteronyssinus Subcutaneous Immunotherapy Does Not Correlate with Specific IgA but with IgG4 in both Serum and Saliva.

BACKGROUND: The role of salivary-specific IgG4 and IgA in subcutaneous immunotherapy (SCIT) is not well defined. We aimed to investigate the change of IgG4 and IgA in both serum and saliva and their correlations with IgE-blocking-factor (IgE-BF) during SCIT. METHOD: 307 Dermatophagoides pteronyssinus (DP) allergic rhinitis and/or asthma patients were recruited for this study. 286 patients received DP-SCIT for 1 year. Twenty-one patients received only symptomatic treatment. DP-, Der p 1-, and Der p 2-specific IgE in serum, specific-IgG4 and Der p 2-specific IgA1 and IgA2 in both serum and saliva were measured at timepoints 0, 4, and 12 months during DP-SCIT. Correlation between salivary and serological IgG4, IgA, and their correlation with DP-specific IgE-BF measured in serum was evaluated. RESULTS: During DP-SCIT, the allergen-specific IgG4 in both saliva and serum increased and correlated significantly, the correlation becomes stronger over the treatment time. DP-specific IgE-BF significantly correlated with DP-specific IgG4 in serum (p < 0.0001) at different timepoints and in saliva at 12 months of SCIT (p < 0.01). No change in Der p 2-specific IgA during DP-SCIT was observed, and the IgA in serum did not correlate with IgA in saliva. There was no correlation between DP IgE-BF and Der p 2-specific IgA in serum or saliva. The control group did not exhibit significant changes in any antibody level measured. CONCLUSION: The IgE blocking activity induced by DP-SCIT treatment correlated with specific IgG4 and not IgA. The IgG4 in saliva correlates with serum IgG4 and can be an alternative immunological marker beyond 1 year of SCIT treatment.

Bioadsorbents from algae residues for heavy metal ions adsorption: chemical modification, adsorption behaviour and mechanism.

Biosorption is an emerging technology for the removal of heavy metals from industrial wastewater by natural or modified biomass. In this study, we proposed a novel protocol for making full use of seaweeds. Brown seaweed Sargassum carpophyllum residue (SCR) and green seaweed Caulerpa lentillifera residue (CLR) were obtained after extraction of the bioactive polysaccharides. The obtained residues were further chemical modified by butanedioic anhydride to obtained respective carboxylated product, named CSCR and CCLR. According to the titration results, CSCR and CCLR contained 2.77 and 2.12 mmol/g of carboxyl group. After modification, the adsorption capacity for metal ions increased by 3-6 times. The adsorption capacity of CSCR for Cu2+, Pb2+, Cd2+ and Mn2+ was 52.37, 107.11, 85.62, and 43.52 mg/g, and that of CCLR was 78.10, 108.80, 87.30 and 57.80 mg/g, respectively. The adsorption was well described by the pseudo-second-order kinetic model and Langmuir adsorption isotherm equation.

Clinical Response to Subcutaneous Dermatophagoides pteronyssinus Immunotherapy in Children with Allergic Rhinitis and Asthma Is Independent of Sensitization to Blomia tropicalis Allergens.

BACKGROUND: Dermatophagoides pteronyssinus (DP) and Blomia tropicalis (BT) are the dominant house dust mites inducing allergic diseases in tropical climates. It is not known whether the efficacy of DP subcutaneous immunotherapy (SCIT) is similar in patients sensitized to DP alone or to both DP and BT. METHOD: Ninety-five children (5-17 years old) affected by asthma with rhinitis and sensitized to both DP and BT received 3 years of DP-SCIT. Clinical symptom and medication scores, serum-specific IgE and IgG4 were evaluated during DP-SCIT. Patients were grouped based on DP and BT co-sensitization or cross-reactivity, according to positive or negative IgE to BT major allergen (BTMA). RESULTS: After 3 years of DP-SCIT, all patients had significant reductions in symptoms and medication use. In all, 65% of the patients were free of asthma symptoms and medication use; in addition, 3% was free of rhinitis symptoms. FEV1 in all patients were greater than 95% of predicted. DP-SCIT induced significant increases in DP- and BT-specific IgG4. In 50% of patients, DP-specific IgG4 increased more than 67-fold. BT-specific IgG4 increased more than 2.5 fold. A moderate correlation (r = 0.48-0.61, p < 0.01) was found between specific IgE against DP and BT in the BTMA- group (n = 34) before and after DP-SCIT, whereas no correlation was found in the BTMA+ group (n = 61). The 2 BTMA groups responded similarly with regard to clinical improvement and increase in specific IgG4 to both DP and BT. No safety finding of concern were reported in either group. CONCLUSION: DP-SCIT may be of clinical benefit to patients with IgE sensitizations to both DP and BT. DP-SCIT induces IgG4 that cross-react with BT allergens.

Self-reported questionnaire survey on the prevalence and symptoms of adverse food reactions in patients with chronic inhalant diseases in Tangshan city, China.

BACKGROUND: The prevalence of adverse food reactions in patients with chronic inhalant diseases has seldom been studied in China. This study is to investigate the prevalence of adverse food reactions and the symptoms caused in respiratory patients. METHODS: Respiratory patients in allergy clinics were asked to complete a questionnaire. Patients' information such as age, gender, family history of allergy, and adverse reactions to a list of 48 foods and the symptoms caused, was recorded. Multivariate analyses were performed to determine the prevalence of adverse food reactions and their associated symptoms. RESULTS: 459 subjects, with an average age of 32 years old, completed the questionnaire; 45.3% were male. Among the 459 subjects, 38.1% (175/459) had an adverse reaction to food: 13.6% had an adverse food reaction to crab, 12.4% had an adverse food reaction to shrimp; and 9.9% had an adverse reaction to shellfish. Peach and nectarine were also shown to be common causative foods with 6.8% of the study group showing an adverse reaction to peach and 5.2% to nectarine. Seafood mainly caused skin symptoms and fruits gave rise to more throat, oral, and gastrointestinal problems. CONCLUSION: The prevalence of adverse food reactions is high for patients with respiratory diseases. This indicates that adverse food reactions should be considered in the treatment and management of patients with chronic inhalant diseases.

CCL18-dependent translocation of AMAP1 is critical for epithelial to mesenchymal transition in breast cancer.

AMAP1 was a GTPase-activating protein that regulates cytoskeletal structures in focal adhesions, circular dorsal ruffles, and promote cell differentiation in tumor cells. But the activation and function of AMAP1 in breast cancer remain largely unexplored. Here we show that AMAP1 was phosphorylated and translocated to plasma membrane and formed a stable complex with Pyk2 in response to CCL18. Moreover, CCL18-dependent AMAP1 translocation interfered the AMAP1-IKK-ß interaction, resulting in nuclear factor-kappaB (NF-κB) activation. Depletion of AMAP1 expression by RNAi efficiently reversed the CCL18-induced epithelial to mesenchymal transition (EMT) of breast cancer cells and as well as CCL18-induced adhesion, migration and invasion. Strikingly, AMAP1 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognosis in breast cancers. Given that AMAP1 mediated CCL18-induce activation of NF-κB and promoted breast cancer metastasis, AMAP1 may represent a therapeutic target for the eradication of breast cancer metastasis.