Characterization of site-specific N-glycosylation signatures of isolated uromodulin from human urine.

Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.

Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins.

The glycoprotein spike (S) on the surface of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a determinant for viral invasion and host immune response. Herein, we characterized the site-specific N-glycosylation of S protein at the level of intact glycopeptides. All 22 potential N-glycosites were identified in the S-protein protomer and were found to be preserved among the 753 SARS-CoV-2 genome sequences. The glycosites exhibited glycoform heterogeneity as expected for a human cell-expressed protein subunit. We identified masses that correspond to 157 N-glycans, primarily of the complex type. In contrast, the insect cell-expressed S protein contained 38 N-glycans, completely of the high-mannose type. Our results revealed that the glycan types were highly determined by the differential processing of N-glycans among human and insect cells, regardless of the glycosites' location. Moreover, the N-glycan compositions were conserved among different sizes of subunits. Our study indicates that the S protein N-glycosylation occurs regularly at each site, albeit the occupied N-glycans were diverse and heterogenous. This N-glycosylation landscape and the differential N-glycan patterns among distinct host cells are expected to shed light on the infection mechanism and present a positive view for the development of vaccines and targeted drugs.

Recent advances on food-grade oleogels: Fabrication, application and research trends.

In order to improve the nutritional and quality characteristics of food, solid fats are widely used in food formulations. With the continuous improvement of consumers' awareness of health in recent years, substantial attempts have been carried out to find substitutes for solid fats to reduce saturated fatty acid content in foods. Oleogels have drawn increasing attention due to their attractive advantages such as easy fabrication, superior fatty acid composition and safe use in food products to satisfy consumers' demands for healthy products. This review provides the latest information on the diversified oleogel systems. The feasibility of oleogel and oleogel-based system as nutraceutical vehicles is elucidated. The type as well as concentration of oleogelators and the synergistic effect between two or more oleogelators are important factors affecting the properties of obtained oleogel. Oleogels used in nutraceutical delivery have been shown to offer increased loading amount, enhanced bioaccessibility and targeted or controlled release. These nutrients wrapped in oleogels may in turn affect the formation and properties of oleogels. Furthermore, the future perspectives of oleogels are discussed. The feasible research trends of food-grade oleogel include oleogel-based solid lipid particle, essential oil-in-oleogel system, delivery of probiotics, nutraceuticals co-delivery and microencapsulated oleogel.

Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress.

Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress play a pivotal role in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). In this study, we found that blueberry-derived exosomes-like nanoparticles (BELNs) could ameliorate oxidative stress in rotenone-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6 mice. Preincubation with BELNs decreased the level of reactive oxygen species (ROS), increased the mitochondrial membrane potential, and prevented cell apoptosis by inducing the expression of Bcl-2 and heme oxygenase-1 (HO-1) and decreasing the content of Bax in rotenone-treated HepG2 cells. We also found that preincubation with BELNs accelerated the translocation of Nrf2, an important transcription factor of antioxidative proteins, from the cytoplasm to the nucleus in rotenone-treated HepG2 cells. Moreover, administration of BELNs improved insulin resistance, ameliorated the dysfunction of hepatocytes, and regulated the expression of detoxifying/antioxidant genes by affecting the distribution of Nrf2 in the cytoplasm and nucleus of hepatocytes of HFD-fed mice. Furthermore, BELNs supplementation prevented the formation of vacuoles and attenuated the accumulation of lipid droplets by inhibiting the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), the two key transcription factors for de novo lipogenesis in the liver of HFD-fed mice. These findings suggested that BELNs can be used for the treatment of NAFLD because of their antioxidative activity.

Application of near-infrared fluorescence imaging in the accurate assessment of surgical margins during breast-conserving surgery.

OBJECTIVE: To evaluate the feasibility and accuracy of near-infrared fluorescence imaging technology for assessing margins during breast-conserving surgery for breast cancer. METHODS: Forty-three breast cancer patients who received surgical treatment at Yijishan Hospital of Wannan Medical College were selected. Before the operation, the patients were administered with an indocyanine green injection of 0.5 mg/kg intravenously 2 h before operation. During and after the operation, all patients underwent surgical margin monitoring with the near-infrared fluorescence imaging system for fluorescence imaging and acquisition of images and quantitative fluorescence intensity. During the operation, the patients' tissue specimens were collected on the upper, lower, inner, outer, apical, and basal sides of the fluorescence boundary of the isolated lesions for pathological examination. RESULTS: Fluorescence was detected in the primary tumor in all patients. The average fluorescence intensities of tumor tissue, peritumoral tissue, and normal tissue were 219.41 ± 32.81, 143.35 ± 17.37, and 105.77 ± 17.79 arbitrary units, respectively (P < 0.05, t test). The signal-to-background ratio of tumor to peritumor tissue and normal tissue was 1.54 ± 0.20 and 2.14 ± 0.60, respectively (P < 0.05, t test). Abnormal indocyanine green fluorescence was detected in 11.6% patients (5/43), including 3 patients with residual infiltrating carcinoma and 2 patients with adenosis with ductal dilatation. CONCLUSION: This study confirms the high sensitivity and specificity of near-infrared fluorescence imaging technology for breast-conserving surgery margin assessment. Near-infrared fluorescence imaging technology can be used as an intraoperative diagnosis and treatment tool to accurately determine the surgical margin and is of important guiding value in breast-conserving surgery for breast cancer.

A nomogram model based on the preoperative clinical characteristics of papillary thyroid carcinoma with Hashimoto's thyroiditis to predict central lymph node metastasis.

OBJECTIVE: Preoperative prediction of central lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT) provides an important basis for surgical decision-making, especially regarding the extent of tumour resection. We aimed to develop and validate a nomogram model for the preoperative assessment of central LN metastasis. METHODS: We retrospectively collected the data of 994 PTC patients with HT who underwent surgery at the West China Hospital from January 2008 to December 2017. Among them, 606 patients who underwent surgeries relatively earlier comprised the training cohort for nomogram development, while the other 388 who underwent surgeries relatively later formed the validation cohort to validate the model's performance. Univariate and multivariate logistic regression analyses were conducted using the data of the two respective cohorts, as well as the data of the combined cohort. The relevant preoperative potential risk factors include demographic characteristics, medical history information, thyroid function test, ultrasound characteristics and BRAF V600E gene detection. A nomogram model was subsequently developed. The performance, discrimination and calibration of the nomogram model were assessed in the training and validation cohorts and in the combined cohort. RESULTS: The central LN metastasis rate of PTC with HT was 49.7% (301/606) and 48.7% (193/388) in the training and validation cohorts, respectively. The univariate and multivariate logistic regression analyses indicated that younger age, normal body mass index, BRAF V600E mutation, larger maximum diameter, left lobe tumour, aspect ratio >1, capsular invasion and calcification were significant risk factors for central LN metastasis in PTC patients with HT. The preoperative nomogram showed good calibration and discrimination for the training and validation cohorts, as well as for the combined data set. CONCLUSION: The nomogram we developed and validated with a comprehensive set of preoperative factors is effective in predicting central LN metastasis in PTC patients with HT.

Geniposide improves insulin resistance through AMPK-mediated Txnip protein degradation in 3T3-L1 adipocytes.

Thioredoxin-interacting protein (Txnip) has emerged as a key regulator of insulin resistance. In this study, we investigated the roles of geniposide and Txnip in insulin resistance in differentiated 3T3-L1 adipocytes. Our results revealed that geniposide markedly enhanced glucose uptake, increased the protein levels of insulin receptor substrate (IRS)-1 and GLUT-1, and prevented the phosphorylation of IRS-1 and Akt Thr308 induced by insulin resistance in 3T3-L1 adipocytes. We also observed that geniposide accelerated protein degradation of Txnip through proteasome pathway, and knockdown of Txnip with small interfering RNA attenuated the effect of geniposide on insulin signaling molecules, implying that Txnip played a pivotal role in the regulation of insulin signaling molecules by geniposide in 3T3-L1 adipocytes. Furthermore, geniposide induced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in the presence of high glucose in differentiated 3T3-L1 adipocytes, while compound C, an inhibitor of AMPK, prevented the effect of geniposide on Txnip degradation and the regulation of glucose uptake and insulin signaling molecules including p-IRS-1, IRS-1, and GLUT-1 in differentiated 3T3-L1 adipocytes. Taken together, all these findings suggest that geniposide improves the insulin signaling defect possibly by AMPK-mediated Txnip degradation in 3T3-L1 adipocytes.

Glyco-CPLL: An Integrated Method for In-Depth and Comprehensive N-Glycoproteome Profiling of Human Plasma.

N-glycoproteins are involved in various biological processes. Certain distinctive glycoforms on specific glycoproteins enhance the specificity and/or sensitivity of cancer diagnosis. Therefore, the characterization of plasma N-glycoproteome is essential for a new biomarker discovery. The absence of suitable analytical methods for in-depth and large-scale analyses of low-abundance plasma glycoproteins makes it challenging to investigate the role of glycosylation. In this study, we developed an integrated method termed Glyco-CPLL, which integrates combinatorial peptide ligand libraries, high-pH reversed-phase prefractionation, hydrophilic interaction chromatography, trypsin and PNGase F digestion, shotgun proteomics, and various analysis software (MaxQuant and pGlyco2.0) for the low-abundance plasma glycoproteomic profiling. Then, we utilized the method to perform a comparative study and to explore papillary thyroid carcinoma-related proteins and glycosylations with reference to healthy controls. Finally, a large and comprehensive human plasma N-glycoproteomic database was established, containing 786 proteins, 369 N-glycoproteins, 862 glycosites, 171 glycan compositions, and 1644 unique intact N-glycopeptides. Additionally, several low-abundance plasma glycoproteins were identified, including SVEP1 (∼0.54 ng/mL), F8 (∼0.83 ng/mL), and ADAMTS13 (∼1.2 ng/mL). These results suggest that this method will be useful for analyzing plasma intact glycopeptides in future studies. Besides, the Glyco-CPLL method has a great potential to be translated to clinical applications. Data are available via ProteomeXchange with identifier PXD016428.

Comparative Glycoproteomic Profiling of Human Body Fluid between Healthy Controls and Patients with Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer among women worldwide. It is confirmed mainly by fine-needle aspiration biopsy (FNAB), an invasive diagnostic method. The key proteins responsible for thyroid hormone biosynthesis are glycosylated. Hence, changes in site-specific glycosylation are associated with thyroid cancer. Integrated quantitative proteomic and glycoproteomic analyses of body fluids from patients with PTC may identify potential noninvasive biomarkers, improve diagnostic accuracy, and elucidate the basic mechanisms of tumor development. In the present study, we demonstrate an integrated, highly reproducible, rapid method involving body fluid proteome and glycoproteome analysis. Moreover, this method may quantitatively profile protein glycosylation. Intact N-glycopeptides from the urine and plasma of healthy controls (HC), PTC, and PTC with Hashimoto's thyroiditis (PHT) were enriched by hydrophilic interaction liquid chromatography. Sialic acid was removed from the N-glycopeptides with trifluoroacetic acid and heat. The desialo-N-glycopeptides were analyzed by HCD-MS/MS using stepped collision energies and several search engines for quantitative profiling. Ninety-two altered proteins and 134 intact N-glycopeptides were isolated from the plasma and urine samples of the three groups (90 samples from 15 subjects). To the best of our knowledge, this study is the first to compare the plasma and urinary proteomes and glycoproteomes of HC, PTC, and PHT. Moreover, we reveal a novel indicator (ratio of fucosylated to nonfucosylated N-glycopeptide or F/NF) through desialo-N-glycopeptide analysis. These differently expressed glycoproteins and F/NF may serve as biomarkers contributing to clinical cancer diagnostics and could be used to improve diagnostic accuracy noninvasively.

Helix B surface peptide reduces sepsis-induced kidney injury via PI3K/Akt pathway.

AIM: Helix B-Surface peptide (HBSP) is the latest discovered erythropoietin (EPO) analogue that can retain the activity of EPO. EPO, which is widely used for treating renal anemia, has recently been proved to have protective effects on ischemia-reperfusion injury of brain, heart and kidney. The protective effects of EPO and HBSP on cardiac function were found in rats with myocardial ischemia. However, the effect of HBSP on sepsis-induced renal injury is still unclear. METHODS: Establishment of rat kidney injury model and treated with HBSP and lipoposaccharide. Renal injury in rats was observed by hematoxylin-eosin staining and injury index score. Levels of serum creatinine (SCr), blood urea nitrogen (BUN) and Cystatin C (Cys C) were detected using fully automatic biochemical analyzer, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß were detected by enzyme-linked immunosorbent assay. Western blot analysis was performed to determine the role of HBSP in phosphatidylinositol 3-kinase (PI3K)/Akt pathway. RESULTS: Acute kidney injury (AKI) appeared after modeling, however, HBSP alleviated the pathological conditions of the kidney injury. In addition, HBSP lowered kidney injury index score in the rats, and decreased the levels of SCr, BUN, Cys C, TNF-α, IL-6 and IL-1ß, moreover, HBSP also showed the effect of activating PI3K/Akt pathway. CONCLUSION: HBSP alleviated lipoposaccharide-induced AKI and improved kidney function of the rats with sepsis. More importantly, the effects of HBSP on lipoposaccharid-induced AKI were realized via activating PI3K/Akt pathway. The findings in the current study provide new insights into the therapeutic mechanism for treating the disease.

The effectiveness of the combined problem-based learning (PBL) and case-based learning (CBL) teaching method in the clinical practical teaching of thyroid disease.

BACKGROUND: This study aimed to evaluate the effectiveness and efficiency of PBL-CBL combined teaching in thyroid surgery and make observations from the students' perspectives, based on their satisfaction with the learning process. METHODS: We prospectively enrolled 354 fourth-year students majoring in clinical medicine, along with 232 residents, from September 2014 to June 2019. These participants were randomly allocated into either the combined PBL-CBL teaching group or the traditional lecture-based classroom group to attend a course about thyroid nodules. Both pre- and post-class quizzes were conducted. An anonymous questionnaire was also administered to both groups to evaluate the students' perceptions and experiences. We compared the two teaching methods among all the students as well as with the fourth-year students and residents in subgroups. RESULTS: The traditional group's pre-class quiz scores were significantly higher than the PBL-CBL group's (as determined by a two-tailed t-test at a 95% confidence interval, T = 16.483, P < 0.001). After class, in the PBL-CBL group, the mean total quiz score and the basic knowledge and case analysis scores increased significantly (P < 0.001). The PBL-CBL group's performance improvement was significantly higher than the traditional group's (increasing from 52.76 to 70.51 vs. from 67.03 to 71.97). Furthermore, the scores for learning motivation, understanding, student-teacher interaction, the final examination, communication skills, clinical thinking skills, self-learning skills, teamwork skills, and knowledge absorption, as measured by the survey, were significantly higher in the PBL-CBL group than in the traditional group (P < 0.001). Meanwhile, the survey scores representing the amount of students' free time the course consumed were significantly lower in the PBL-CBL group than in the traditional group (P < 0.001). CONCLUSIONS: PBL combined with CBL may be an effective method for improving medical students' and residents' performance and enhancing their clinical skills.

The effect and mechanism of millepachine-disrupted spindle assembly in tumor cells.

Millepachine (MIL) is a bioactive natural product that shows great potential for cancer treatment. Previous studies showed that MIL was a novel cancer drug candidate with a special structure. To provide reference for the research and development of MIL, we further investigated the mechanism of MIL inducing G2/M arrest and found MIL disrupted spindle assembly in tumor cells. In this study, we investigated the disrupting spindle assembly effects of MIL with a focus on its potential mechanism of action. First, we indicated that MIL did not inhibit microtubule polymerization from the results of in-vivo microtubule nucleation assay and microtubule polymerization in-vitro assay but delayed this process by inhibiting the production of ATP in tumor cells. Thereafter, we investigated the effect of MIL on the mitotic spindle. We found that MIL induced multipolar spindles by inhibiting the activity of Eg5 and inhibited mitotic spindle formation and chromatin condensation by the activation of the spindle assembly checkpoint (SAC) in tumor cells. These results established a novel function of MIL in regulating the assembly of mitotic spindle. As Eg5 and SAC are antitumor targets, effect of MIL on the Eg5 protein and SAC activation hinted that MIL has novel application in the development of antitumor drugs.

Subclinical hypothyroidism would not lead to female sexual dysfunction in Chinese women.

BACKGROUND: There is dearth of research about female sexual dysfunction (FSD), especially in China, because of conservative beliefs. Previous studies indicated the relationship between subclinical hypothyroidism and anxiety and depression. However, there is dearth of research regarding the relationship between subclinical hypothyroidism and FSD in Chinses women. METHOD: A hospital-based research was conducted. Female sexual function was measured by CVFSFI which includes 19 items. Participants were identified as FSD if CVFSFI ≤ 23.45. Logistics analysis was used to determine risk factor of FSD. All of them finished CVFSFI, Beck Depression Inventory (BDI) self-reporting questionnaires and had thyroid hormone tests. Based on presence and absence of subclinical hypothyroidism, participants were divided into two groups. Risk factors of FSD were identified. RESULT: One thousand one hundred nineteen participants with CVFSFI score 25.8 ± 3.9 were enrolled in final analysis. Incidence of subclinical hypothyroidism and FSD in Chinese women was 15.0% and 26.5% respectively. There were no significant difference between subclinical hypothyroidism and control group in FSFI score and prevalence of FSD. Age, Depression (medium risk) was identified as risk factors for nearly all types of FSD, and Income (ranges from 40,000 to 100,000 RMB/year) as protective factor. Subclinical hypothyroidism had no significant relationship with FSD. CONCLUSION: Subclinical hypothyroidism is not the risk factor for FSD in urban women of China.

Hypomagnesemia predicts postoperative biochemical hypocalcemia after thyroidectomy.

BACKGROUND: To investigate the role of magnesium in biochemical and symptomatic hypocalcemia, a retrospective study was conducted. METHODS: Less-than-total thyroidectomy patients were excluded from the final analysis. Identified the risk factors of biochemical and symptomatic hypocalcemia, and investigated the correlation by logistic regression and correlation test respectively. RESULTS: A total of 304 patients were included in the final analysis. General incidence of hypomagnesemia was 23.36%. Logistic regression showed that gender (female) (OR = 2.238, p = 0.015) and postoperative hypomagnesemia (OR = 2.010, p = 0.017) were independent risk factors for biochemical hypocalcemia. Both Pearson and partial correlation tests indicated there was indeed significant relation between calcium and magnesium. However, relative decreasing of iPTH (>70%) (6.691, p < 0.001) and hypocalcemia (2.222, p = 0.046) were identified as risk factors of symptomatic hypocalcemia. The difference remained significant even in normoparathyroidism patients. CONCLUSIONS: Postoperative hypomagnesemia was independent risk factor of biochemical hypocalcemia. Relative decline of iPTH was predominating in predicting symptomatic hypocalcemia.

Foam-templated oleogels constructed by whey protein isolate and xanthan gum: Multiple-effect delivery vehicle for Antarctic krill oil.

To address the limitations of Antarctic krill oil (AKO) such as easy oxidation, unacceptable fishy flavor and low bioaccessibility of astaxanthin in it, a multiple-effect delivery vehicle for AKO is needed. In this study, whey protein isolate (WPI) and xanthan gum (XG) were utilized to construct AKO into oleogels by generating foam-templates. The effects of the concentration of XG on the properties of foam, cryogel and the corresponding oleogels were investigated, and the formation mechanism of oleogel was discussed from the perspective of the correlation between foam-cryogel-oleogel. The results demonstrated that with the increase of the concentration of XG, the foam stability was improved, the cryogel after freeze drying had a more uniform network structure and superior oil absorption ability, and the corresponding oleogel had excellent oil holding ability after oil absorption. The AKO oleogels showed superior oxidative stability compared with AKO. The in vitro digestion experiments demonstrated that the bioaccessibility of the astaxanthin in this oleogel was also considerably higher than that in AKO. In addition, this oleogel had masking effect on the odor-presenting substances in AKO, while retaining other flavors of AKO. The foam-templated oleogel can be considered as a multiple-effect vehicle for AKO to facilitate its application in food products. This study provides theoretical basis and data support for the development and utilization of novel vehicle for AKO, broadening the application of AKO in the field of food science.

Effect of Radioactive Iodine Therapy on Cancer-Specific Survival of Papillary Thyroid Cancer Tall Cell Variant.

CONTEXT: Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial. OBJECTIVE: This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database. METHODS: We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS. RESULTS: After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results. CONCLUSION: RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings.

Effect and Interactions of BRAF on Lymph Node Metastasis in Papillary Thyroid Carcinoma With Hashimoto Thyroiditis.

CONTEXT: The role of B-Raf proto-oncogene (BRAF) in papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT) is unknown. OBJECTIVE: We aimed to explore risk factors affecting lymph node (LN) metastasis and interaction effect of BRAF in PTC patients with HT. METHODS: We retrospectively collected the data of 994 PTC patients with HT who underwent surgery at the West China Hospital. We analyzed the correlations between preoperative characteristics and LN metastasis in overall, and different BRAFV600E-mutation patients. Logistic regression was applied to analyze the risk factors for LN metastasis. Finally, we performed an interaction effect analysis to identify the interaction effect of BRAF. RESULTS: The overall LN metastasis rate was 52.71% (524/994); the overall BRAF mutation rate was 26.9% (268/994). BRAF mutation rates were significantly different in LN metastasis and nonmetastasis patients (31.7% vs 21.5%; P < .001). In all 994 patients, age, body mass index (BMI), hypertension, tumor maximum diameter, BRAF mutation, tumor location, aspect ratio, calcification, and extrathyroidal invasion were risk factors for LN metastasis (P < .05). In BRAF-mutant patients, smoking, hypertension, maximum diameter, calcification, and multifocality were risk factors for LN metastasis (P < .05). In BRAF wild-type patients, age, BMI, maximum diameter, tumor location, aspect ratio, tumor shape, calcification, and extrathyroidal invasion were risk factors (P < .05). Additionally, we found statistically significant interactions between BRAF and BMI, hypertension, maximum diameter, and calcification (P < .05), suggesting the potential interaction effect of BRAF. CONCLUSION: BRAF is a risk factor for LN metastasis in PTC with HT. Meanwhile, BRAF can interact with age, BMI, hypertension, and calcification, which together influence LN metastasis.

Low-temperature CO preferential oxidation in H2-rich stream over Indium modified Pd-Cu/Al2O3 catalyst.

The impact of Indium (In) doping upon the catalytic performance of Pd-Cu/Al2O3 for carbon monoxide preferential oxidation (CO-PROX) in hydrogen (H2) rich atmosphere at low temperature has been studied. A series of catalysts with extremely low palladium (Pd) loading (0.06 wt%) are synthesized by the facile co-impregnation method. When the In/copper (Cu) atomic ratio equals 0.25, Pd-Cu-In0.25/Al2O3 can keep 40% CO conversion and 100% carbon dioxide (CO2) selectivity at least 120 min at 30 °C, which is significantly superior to the catalytic performance of Pd-Cu/Al2O3. The elaborate characterization findings reveal that the added In species to Pd-Cu/Al2O3 causes Indium oxide (In2O3) to generate, which produces the interaction of In2O3 with Pd-Cu/Al2O3, further promoting the dispersion of copper chloride hydroxide (Cu2Cl(OH)3). Moreover, the modification of In facilitates the re-oxidation of Pd0 to Pd+ through reducing the formation of palladium hydride (PdHx) during the CO-PROX reaction. Meanwhile, the addition of In leads to the decrease of Cu+ electron cloud density, making it easier to be oxidized to Cu2+. Collectively, the easy re-oxidation of Pd0 and Cu+ is favorable to fulfill the Wacker cycle between Pd and Cu species, thus improving the catalytic performance for CO-PROX.

A Personalized 3D-Printed Model for Preoperative Evaluation in Thyroid Surgery.

The anatomic structure of the surgical area of thyroid cancer is complex. It is very important to comprehensively and carefully evaluate the tumor location and its relation with the capsule, trachea, esophagus, nerves, and blood vessels before operation. This paper introduces an innovative 3D-printed model establishment method based on computerized tomography (CT) DICOM images. We established a personalized 3D-printed model of the cervical thyroid surgery field for each patient who needed thyroid surgery to help clinicians evaluate the key points and difficulties of the surgery and select the operation methods of key parts as a basis. The results showed that this model is conducive to preoperative discussion and the formulation of operation strategies. In particular, as a result of the clear display of the recurrent laryngeal nerve and parathyroid gland locations in the thyroid operation field, injury to them can be avoided during surgery, the difficulty of thyroid surgery reduced, and the incidence of postoperative hypoparathyroidism and complications related to recurrent laryngeal nerve injury reduced too. Moreover, this 3D-printed model is intuitive and aids communication for the signing of informed consent by patients before surgery.

Sensitivities evaluation of five radiopharmaceuticals in four common medullary thyroid carcinoma metastatic sites on PET/CT: a network meta-analysis and systematic review.

OBJECTIVES: Detecting medullary thyroid carcinoma (MTC) metastatic lesions accurately is still a challenge for clinicians. PET/computed tomography (PET/CT) seems to be the most effective method in recent years. However, the sensitivity of each radiopharmaceutical varies greatly in different metastatic sites. We aim to investigate and compare five novel and common PET or PET/CT radiopharmaceutical sensitivities at the four most frequent metastatic sites by network meta-analysis. METHODS: We searched for studies evaluating PET/CT radiopharmaceutical sensitivities at different metastatic sites in PubMed, Web of Science, Embase, and Cochrane Library. The risk bias was analyzed, and publication bias was accessed by funnel plot asymmetry tests. We performed both global inconsistency and local inconsistency tests by evaluating the agreement between direct and indirect comparisons. Then, we made pairwise meta-analyses and network meta-analyses for each metastatic site. Finally, we performed the surface under the cumulative ranking curves (SUCRA) and calculated the SUCRA values to rank the probability of each radiopharmaceutical being the most sensitive method. RESULTS: In our results, 243 patients from 9 clinical studies which accessed sensitivities of different radiopharmaceuticals in MTC metastatic sites were included. For lymph nodes and liver, TF2/ 68 Ga-SSM288 showed the highest SUCRA values (0.974 in lymph nodes, 0.979 in liver). The SUCRA values for 18 F-DOPA and 68 Ga-SSA for bone metastatic lesions were nearly identical (0.301 and 0.319, respectively) and were higher than the other three radiopharmaceuticals. For lung lesions, 11 C-methionine had the highest SUCRA value (0.412). CONCLUSION: TF2/ 68 Ga-SSM288 had the best sensitivity in lymph nodes and liver lesions. 11 C-methionine was most sensitive in lung lesions. While 18 F-DOPA and 68 Ga-SSA had familiar sensitivities to be the best two radiopharmaceuticals.