The transcription factor GATA6 accelerates vascular smooth muscle cell senescence-related arterial calcification by counteracting the role of anti-aging factor SIRT6 and impeding DNA damage repair.

Arterial calcification is a hallmark of vascular pathology in the elderly and in individuals with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs), after attaining a senescent phenotype, are implicated in the calcifying process. However, the underlying mechanism remains to be elucidated. Here, we reveal an aberrant upregulation of transcriptional factor GATA6 in the calcified aortas of humans, mice with CKD and mice subjected to vitamin D3 injection. Knockdown of GATA6, via recombinant adeno-associated virus carrying GATA6 shRNA, inhibited the development of arterial calcification in mice with CKD. Further gain- and loss-of function experiments in vitro verified the contribution of GATA6 in osteogenic differentiation of VSMCs. Samples of human aorta exhibited a positive relationship between age and GATA6 expression and GATA6 was also elevated in the aortas of old as compared to young mice. Calcified aortas displayed senescent features with VSMCs undergoing premature senescence, blunted by GATA6 downregulation. Notably, abnormal induction of GATA6 in senescent and calcified aortas was rescued in Sirtuin 6 (SIRT6)-transgenic mice, a well-established longevity mouse model. Suppression of GATA6 accounted for the favorable effect of SIRT6 on VSMCs senescence prevention. Mechanistically, SIRT6 inhibited the transcription of GATA6 by deacetylation and increased degradation of transcription factor Nkx2.5. Moreover, GATA6 was induced by DNA damage stress during arterial calcification and subsequently impeded the Ataxia-telangiectasia mutated (ATM)-mediated DNA damage repair process, leading to accelerated VSMCs senescence and osteogenic differentiation. Thus, GATA6 is a novel regulator in VSMCs senescence. Our findings provide novel insight in arterial calcification and a potential new target for intervention.

Tetraspanin 1 regulates papillary thyroid tumor growth and metastasis through c-Myc-mediated glycolysis.

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis. Tetraspanin 1 (TSPAN1) is a member of the tetra-transmembrane protein superfamily and has been implicated in tumorigenesis and cancer metastasis in various studies. However, the role of TSPAN1 in PTC tumor development remains unclear. In this study, we aimed to investigate the impact of TSPAN1 on PTC cell behavior. Our results demonstrate that knockdown of TSPAN1 inhibits PTC cell proliferation, migration, and invasion, while overexpression of TSPAN1 has the opposite effect. These findings suggest that TSPAN1 might play a role in the tumorigenesis and invasiveness of PTC. Mechanistically, we found that TSPAN1 activates the ERK pathway by increasing its phosphorylation, subsequently leading to upregulated expression of c-Myc. Additionally, we observed that TSPAN1-ERK-c-Myc axis activation promotes glycolytic activity in PTC cells, as evidenced by the upregulation of glycolytic genes such as LDHA. Taken together, our findings indicate that TSPAN1 acts as an oncogene in PTC by regulating glycolytic metabolism. This discovery highlights the potential of TSPAN1 as a promising therapeutic target for PTC treatment. Further research in this area could provide valuable insights into the development of targeted therapies for PTC patients.

Burden, Trends, and Inequalities of Heart Failure Globally, 1990 to 2019: A Secondary Analysis Based on the Global Burden of Disease 2019 Study.

Background Heart failure is a public health issue worldwide. However, no comprehensive study on the global burden of heart failure and its contributing causes has been reported. The present study aimed to quantify the burden, trends, and inequalities of heart failure globally. Methods and Results Heart failure data were extracted from the Global Burden of Diseases 2019 study. The number of cases, age-standardized prevalence, and years lived with disability in different locations from 1990 to 2019 were presented and compared. Joinpoint regression analysis was performed to assess trends in heart failure from 1990 to 2019. In 2019, the global age-standardized prevalence and years lived with disability rates for heart failure were 711.90 (95% uncertainty interval [UI], 591.15-858.29) and 63.92 (95% UI, 41.49-91.95) per 100 000 population, respectively. In general, the age-standardized rate decreased globally at an average annual percentage change of 0.3% (95% UI, 0.2-0.3). However, the rate increased at an average annual percentage change of 0.6% (95% UI, 0.4-0.8) from 2017 to 2019. Several nations and territories demonstrated an increased trend from 1990 to 2019, especially in less-developed countries. Ischemic heart disease and hypertensive heart disease accounted for the highest proportion of heart failure in 2019. Conclusions Heart failure remains a major health problem, with increased trends possible in the future. Efforts for prevention and control of heart failure should focus more on less-developed regions. It is essential to prevent and treat primary diseases such as ischemic heart disease and hypertensive heart disease for the control of heart failure.

Dental Diseases Increase Risk of Aortic Arch Calcification Independent of Renal Dysfunction in Older Adults: Shenzhen Community Cohort Study.

Many studies have documented that dental diseases were associated with an increased risk of cardiovascular diseases. Aortic arch calcification (AoAC) is a powerful predictor of cardiovascular diseases. However, whether the status of dental health is associated with AoAC is still unknown. 9463 participants over the age of 60 from Shenzhen community centers were included in the cross-sectional analysis. Physical examination data, blood biochemical tests, and AoAC scores calculated by chest radiography were collected and analyzed. Among them, 2630 participants were followed up for AoAC progression up to 36 months. Participants with AoAC suffered more tooth loss than those without AoAC (77.62% vs. 72.91%; p < 0.001). Association rule analysis suggested a strong association between dental diseases and AoAC. Tooth loss or decay increased the risk of AoAC progression (HR 1.459; 95%CI 1.284−1.658) after adjusting other risk factors including renal dysfunction. Dental diseases are potential predictors for AoAC in elderly people, which are independent of renal dysfunction.

Efficacy and safety of preoperative transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The aim of the study was to compare preoperative transcatheter arterial chemotherapy (TACE) plus liver resection (LR) with liver resection (LR) alone for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, Embase, Cochrane library, web of science and China National Knowledge Infrastructure (CNKI) were searched from their initiation until 24 August 2021. Eligible languages were English and Chinese. This study includes only RCT and cohort studies. The primary outcome was the prognostic factors including overall survival rate (OS), disease-free survival (DFS), recurrence-free survival (RFS), and we also research the operative time, intraoperative blood loss, and postoperative complication. RESULTS: Twenty-nine trials (2 RCTs and 27 cohorts) were included, containing a total of 22023 patients, compared with hepatic resection, preoperative TACE plus LR shows the benefit of RFS (Hazard Ratio (HR)=0.80, 95%CI = [0.73-0.88], p < .001), and the combined therapy was associated with a higher OS for patients with HCC in Barcelona Clinic Liver Cancer (BCLC) B stage (HR = 0.76, 95%CI = [0.60-0.96], p = .024). In terms of safety, combination therapy is related to less intraoperative blood loss (Weighted Mean Difference (WMD)=-11.17, 95%CI = [-21.79 to -0.54], p = .039); and there's no statistical significance in postoperative complication (Risk Ratio (RR)=0.99, 95%CI= [0.90-1.08], p = 0.771) and operative time (WMD = 7.57, 95%CI = [-5.07 to 20.20], p = .240). CONCLUSION: TACE prior to surgery should be recommended as a routine treatment for HCC patients, especially BCLC B stage HCC, in view of its benefits for RFS and OS. Large, multicenter, and blinded randomized trials should be performed to confirm these findings.

Coronary Artery Disease and Atrial Fibrillation: A Bidirectional Mendelian Randomization Study.

Background: Several works of observational clinical research indicate that coronary artery disease (CAD) and atrial fibrillation (AF) aggravate each other. However, it is unknown whether these associations reveal independent causal processes. Objective: The present study aimed to evaluate causal associations between CAD and AF using two-sample Mendelian randomization (TSMR) analysis. Methods: Summary-level Genome-wide association study (GWAS) data for CAD were obtained from the CARDIoGRAMplusC4D consortium, including 60,801 patients and 123,504 controls. General data for AF were acquired from the largest meta-analysis, comprising of 60,620 patients with AF and 970,216 non-cases. After data harmonization, three different methods­inverse-variance weighted (IVW), MR-Egger, and weighted-median­were applied for TSMR analysis. Results: The calculated ORs (95% CIs) for AF using IVW, MR-Egger, and weighted-median analysis were 1.11 (1.05, 1.17; p-value < 0.001), 1.14 (1.00, 1.29; p-value = 0.049), and 1.13 (1.08, 1.19; p-value < 0.001), respectively; for CAD, the results were 1.01 (0.97, 1.04; p-value = 0.76), 0.95 (0.89, 1.02; p-value = 0.15), and 1.00 (0.95, 1.05; p-value = 0.97). Conclusion: This comprehensive TSMR analysis provides evidence that patients with CAD are associated with an increased risk of AF. However, no causal association was found between patients with AF and the risk of CAD. These findings benefit clinical decision-making. Early heart-rhythm monitoring should be performed in patients with CAD. The prevention and treatment of AF complications such as thrombosis may be essential to reduce the incidence of CAD in AF patients.

Capsaicin Attenuates Arterial Calcification Through Promoting SIRT6-Mediated Deacetylation and Degradation of Hif1α (Hypoxic-Inducible Factor-1 Alpha).

BACKGROUND: Sustained Hif1α (hypoxic-inducible factor-1 alpha) accumulation plays a central role in osteogenic transdifferentiation and subsequent calcification. Capsaicin, the potent agonist of TRPV1 (transient receptor potential vanilloid type 1), was found to mitigate hypoxic-related injury and reverse phenotypic switch of vascular smooth muscle cells. However, its role in arterial calcification and the underlying mechanisms remain unexplored. METHODS: We used data from Multi-Ethnic Study of Atherosclerosis to examine the association of coronary artery calcification and chili consumption. Chronic kidney disease mice and high phosphate-induced vascular smooth muscle cells calcification models were established to investigate the anticalcification effect of capsaicin, evaluated by calcium deposition and changes in phenotype markers. RESULTS: Chili consumption was negatively correlated with coronary artery calcification and conferred a smaller progression burden during follow-up. Capsaicin reduced calcium deposition and osteogenic transdifferentiation both in vivo and in vitro. Using siTRPV1 (small interfering RNA and the antagonist of TRPV1), the anticalcification effect of capsaicin was abrogated. Hif1α was increased in phosphate-treated vascular smooth muscle cells and its degradation was accelerated by capsaicin. Retaining Hif1α stability using cobalt chloride (CoCl2) or MG132 abolished the protective effect of capsaicin. We further identified an increased expression of SIRT6 (Sirtuin 6) in response to capsaicin and confirmed the physical interaction between SIRT6 and Hif1α. Acetylated Hif1α was decreased, whereas hydroxylated Hif1α was increased under capsaicin treatment. Using immunohistochemistry analysis, we observed increased SIRT6 and reduced Hif1α in both SIRT6 transgenic and capsaicin-treated chronic kidney disease mice. CONCLUSIONS: Capsaicin facilitates deacetylation and degradation of Hif1α by upregulating SIRT6, which inhibits osteogenic transdifferentiation and protects against arterial calcification. These data highlight a promising therapeutic target for the management of arterial calcification.

Dissecting the Association of Genetically Predicted Neuroticism with Coronary Artery Disease: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Observational studies on the association between neuroticism and coronary artery disease (CAD) are still rare, and the results of existing studies are not consistent. The present study aimed to explore causal associations of neuroticism with CAD. METHODS: The summary-level data of GWAS for neuroticism and 12 items used to assess neuroticism were extracted from the UK Biobank, and included up to 380,506 participants. The general data for CAD were obtained from the CARDIoGRAMplusC4D consortium, which assembled 60,801 CAD patients and 123,504 non-cases. Single-nucleotide polymorphisms associated with neuroticism and 12 items at genome-wide significance were explored as instrumental variables. Two-sample Mendelian randomization (TSMR) analyses were performed to evaluate causal associations amongst the genetically predicted neuroticism and 12 items with CAD. RESULTS: The present TSMR study did not reveal the genetic association of neuroticism with CAD. The calculated ORs for CAD using inverse-variance weighted, weighted median, and MR-Egger analysis were 1.12 (p-value = 0.187), 0.99 (p-value = 0.943), and 0.82 (p-value = 0.683), respectively. Further TSMR analysis of 12 dichotomous items for assessing neuroticism suggested that mood swings genetically increased the risk of CAD (OR = 1.67, p-value < 0.001). CONCLUSIONS: This study reported no genetically causal association of neuroticism with CAD. The present study also found that mood swings may genetically increase the risk of CAD. These findings may highlight the potential of mood control as a preventive measure for CAD.

Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression.

Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2-/- and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.

Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4.

Background: Atrial fibrillation (AF) is the most common tachyarrhythmia around the world. Cancer is one of the main causes of death worldwide. A recent study demonstrated that cancer was associated with an increased incidence of AF. In the present study, we aimed to explore possible mechanisms and potential common therapeutic targets between AF and cancer. Methods: Differentially expressed proteins between AF and sinus rhythm were identified utilizing proteomics analysis. Weighted gene correlation network analysis was applied to cluster proteins into different modules and investigate associations between modules and AF. Hub immune-related genes were selected via InnateDB database and verified using qRT-PCR. RNA sequencing and clinical data of 33 different cancer types were achieved from The Cancer Genome Atlas (TCGA). The correlations between ANXA4 expression and the prognosis were calculated utilizing Cox regression analysis and Kaplan-Meier survival analysis. Spearman's rank correlation test was used to assess associations between ANXA4 and immune infiltration and DNA methylation. Enrichment analysis was performed through gene ontology and gene set enrichment analysis (GSEA). Results: ANXA4 was identified as hub immune-related gene between AF and sinus rhythm. Expression levels of ANXA4 increased in diverse cancer types. Survival analysis suggested prognostic significance of ANXA4 expression levels in various cancer types. Immune correlation analysis indicated that ANXA4 expression levels were associated with tumor immune infiltration in most cancer types. ANXA4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. GSEA results indicated that high ANXA4 expression groups were mainly enriched in peroxisome, bile acid biosynthesis, and p53 pathway. Conclusion: ANXA4 was identified as a hub immune-related gene in AF, which has never been reported. Pan-cancer analysis indicated its potential as a novel clinical prognostic marker and therapeutic target in diverse cancer types. ANXA4 might play crucial roles in AF and cancer, and targeted therapy for ANXA4 might reduce the incidence of AF in cancer patients.

ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease.

Vascular calcification (VC) predicts cardiovascular morbidity and mortality in chronic kidney disease (CKD). To date, the underlying mechanisms remain unclear. We detected leukocyte DNA N6-methyladenine (6mA) levels in patients with CKD with or without aortic arch calcification. We used arteries from CKD mice infected with vascular smooth muscle cell-targeted (VSMC-targeted) adeno-associated virus encoding alkB homolog 1 (Alkbh1) gene or Alkbh1 shRNA to evaluate features of calcification. We identified that leukocyte 6mA levels were significantly reduced as the severity of VC increased in patients with CKD. Decreased 6mA demethylation resulted from the upregulation of ALKBH1. Here, ALKBH1 overexpression aggravated whereas its depletion blunted VC progression and osteogenic reprogramming in vivo and in vitro. Mechanistically, ALKBH1-demethylated DNA 6mA modification could facilitate the binding of octamer-binding transcription factor 4 (Oct4) to bone morphogenetic protein 2 (BMP2) promoter and activate BMP2 transcription. This resulted in osteogenic reprogramming of VSMCs and subsequent VC progression. Either BMP2 or Oct4 depletion alleviated the procalcifying effects of ALKBH1. This suggests that targeting ALKBH1 might be a therapeutic method to reduce the burden of VC in CKD.

Role of gut microbiota-derived metabolites on vascular calcification in CKD.

The interaction between gut microbiota and the host has gained widespread concern. Gut microbiota not only provides nutrients from the ingested food but also generates bioactive metabolites and signalling molecules to impact host physiology, especially in chronic kidney disease (CKD). The development of CKD, accompanied by changed diet and medication, alters the gut flora and causes the effect in distant organs, leading to clinical complications. Vascular calcification (VC) is an actively regulated process and a high prevalence of VC in CKD has also been linked to an imbalance in gut microbiota and altered metabolites. In this review, we focused on gut microbiota-derived metabolites involved in VC in CKD and explained how these metabolites influence the calcification process. Correcting the imbalance of gut microbiota and regulating microbiota-derived metabolites by dietary modification and probiotics are new targets for the improvement of the gut-kidney axis, which indicate innovative treatment options of VC in CKD.

Aldosterone enhances high phosphate-induced vascular calcification through inhibition of AMPK-mediated autophagy.

It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)-enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α-SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3-MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate-activated protein kinase (AMPK) by Compound C attenuated Aldo/MR-enhanced VC. These results suggested that Aldo facilitates high Pi-induced VSMC osteogenic phenotypic switch and calcification through MR-mediated signalling pathways that involve AMPK-dependent autophagy, which provided new insights into Aldo excess-associated VC in various settings.

BIRC7 promotes epithelial-mesenchymal transition and metastasis in papillary thyroid carcinoma through restraining autophagy.

Papillary thyroid carcinoma (PTC) is the most common cancer of the endocrine system, which is usually associated with a favorable therapeutic response and prognosis. However, metastatic spreading occurs in around 5% of the PTC patients. Identification of molecular markers could early predict the metastatic potential, which is essential for reducing the patient's overtreatment. Baculoviral IAP Repeat Containing 7 (BIRC7) is an inhibitor of apoptosis protein (IAP) family gene that is known to be linked to tumor progression, but its role in the setting of PTC metastasis remains unknown. This study, therefore, aims to explore the role of BIRC7 in the metastasis and autophagy of PTC and elucidate its underlying molecular mechanisms. BIRC7 expression was assessed in fresh samples of human PTC and normal tissues via qRT-PCR and immunohistochemistry. In addition, BIRC7 was overexpressed and silenced in PTC cell lines followed by transmission electron microscopy, western blotting, immunofluorescence microscopy, wound healing and invasion assays. We further explored the relevance of BIRC7 in vivo using a tumor xenograft model. Our results demonstrated that BIRC7 plays a pro-invasive role in PTC. BIRC7 expression is significantly upregulated in PTC compared with matched thyroid normal tissues. In addition, we found that BIRC7 knockdown induced a significant reduction in PTC cell EMT and metastasis in vitro and in vivo, while overexpression of BIRC7 markedly enhanced PTC cell migration and invasion. Moreover, our data showed that BIRC7 was able to suppress autophagy through modulating the expression of ATG5 and BECN1, and that this suppression is responsible for BIRC7 silence induced suppression of EMT and metastasis of PTC cell. We further found that targeting both BIRC7 and mTOR enhances autophagy in PTC cells and to achieve synergistic antimetastatic efficacy in vitro and in vivo. These findings indicate that the suppression of autophagy by BIRC7 drives the invasion and metastasis of PTC cells, thus suggesting that the activation of autophagy may inhibit metastasis of PTC with high BIRC7 expression.

Application of Continuous and Intermittent Intraoperative Nerve Monitoring in Thyroid Surgery.

BACKGROUND: Whether continuous intraoperative nerve monitoring (C-IONM) can further reduce the incidence of recurrent laryngeal nerve injury compared with intermittent intraoperative nerve monitoring (I-IONM) in high-risk thyroid surgery is still controversial. This observational study aimed to evaluate the incidence of vocal cord paralysis (VCP) in high-risk thyroid surgeries performed with I-IONM and C-IONM. MATERIALS AND METHODS: High-risk thyroid surgical patients operated with I-IONM or C-IONM by the same group of surgeons in the thyroid surgery department of our institution between January 2014 and February 2018 were analyzed. Differences in the incidence rates of temporary and permanent VCP between the two groups were compared. A P-value < 0.05 was considered statistically significant. RESULTS: A total of 344 patients who underwent high-risk thyroid surgery (550 nerves at risk [NARs]) were observed, with 238 patients (374 NARs) operated with I-IONM and 106 patients (173 NARs) operated with C-IONM. The incidence of temporary and permanent VCP was 1.9% (7/374) and 0.8% (3/374) in the I-IONM group and 1.2% (2/173) and 0% (0/173) in the C-IONM group, respectively, showing no statistical difference (P = 0.726 and P = 0.555). The incidence rate of impending recurrent laryngeal nerve injuries successfully prevented in the C-IONM group was 5.2% (9/173). CONCLUSIONS: Both I-IONM and C-IONM are equally safe and effective in high-risk thyroid surgery. C-IONM can help predict impending recurrent laryngeal nerve injury in real time and has a good warning feature, thereby minimizing critical maneuvers in high-risk thyroid surgery.

Do Symptoms and Serum Calcium Levels Affect the Results of Surgical Treatment of Primary Hyperparathyroidism?

INTRODUCTION: The purpose of this study was to investigate the difference in surgical outcomes between symptomatic and asymptomatic patients with primary hyperparathyroidism (PHPT) and between patients with high serum calcium and those with normal blood calcium, as well as to explore the epidemiological trend of PHPT in northern China. METHODS: Clinicopathologic data of 197 patients (50 men and 147 women) with PHPT who underwent surgery at the First Affiliated Hospital of Harbin Medical University from 2008 to 2017 were analyzed. Changes in clinicopathology were compared among different subgroups of patients. Patients were categorized into subgroups based on serum calcium levels, whether or not they presented with symptoms, and admission time. RESULTS: Of the total patients, 82.23% had hypercalcemic primary hyperparathyroidism (HCPHPT), 17.77% had normocalcemic primary hyperparathyroidism (NCPHPT), 45.18% had symptomatic primary hyperparathyroidism (SPHPT), and 54.82% had asymptomatic primary hyperparathyroidism (ASPHPT). Seventy-seven cases of PHPT involved thyroid nodules, with 22 confirmed as papillary thyroid carcinoma, and 29 confirmed as nodular goiter. There was no significant difference in the success rate of surgery, postoperative recurrence rate, and the symptoms of temporary hypocalcemia between the HCPHPT and NCPHPT groups, and between the SPHPT and ASPHPT groups. The incidence of PHPT has increased threefold since 2013. CONCLUSIONS: Symptoms and serum calcium levels did not affect the results of surgical treatment for PHPT. The incidence of PHPT in northern China is increasing. Moreover, PHPT manifestation has shifted from the symptomatic to the asymptomatic form. Thyroid surgery should be performed in PHPT patients with thyroid nodules.

Development and validation of a preoperative prediction model for follicular thyroid carcinoma.

OBJECTIVE: The low pre- and intraoperative diagnostic rates in follicular thyroid carcinoma (FTC) often lead to inadequate surgical resection and necessitate further completion surgery. Therefore, the preoperative prediction of FTC in thyroid nodules is essential. DESIGN AND PATIENT: Patients were categorized into two data sets: the modelling data set, which included 3649 patients admitted to our centre between January 2014 and December 2016, and the validation data set, which included 1253 patients admitted between January and December 2017. Patient data from the FTC and non-FTC groups were initially included in a modelling data set to establish a preoperative prediction model. This model was subsequently employed in a validation data set for external validation of the predictive value. The positivity rate for FTC predicted by the model was compared with that of the intraoperative frozen sections. RESULTS: The preoperative serum thyroglobulin level, nodule diameter, calcification status, solidity and blood supply were selected as predictors for the model. The regression equation was as follows: Y = 0.010 × (thyroglobulin level) + 0.556 × (nodule diameter) + 0.675 × (calcification status) + 2.355 × (nodule component) + 1.072*(blood flow) - 9.787. The model positively predicted FTC at values of Y ≥ -4.11. The accuracy, sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of the prediction model were 89.2%, 90.2%, 87.7%, 39.2 and 0.11, respectively. External validation of the model demonstrated acceptable results. The positive prediction rate of the model was 90.7% (78/86), which was significantly higher than that of the intraoperative frozen sections (10.5% [9/86]; P < 0.0001). CONCLUSIONS: We successfully established and validated a simple and reliable preoperative prediction model for FTC using the preoperative thyroglobulin level and ultrasonographic features of the thyroid nodules. This model may improve the preoperative evaluation of FTC in clinical settings and facilitate the development of a reasonable surgical programme for FTC.

The Emerging Role of Mesenchymal Stem Cells in Vascular Calcification.

Vascular calcification (VC), characterized by hydroxyapatite crystal depositing in the vessel wall, is a common pathological condition shared by many chronic diseases and an independent risk factor for cardiovascular events. Recently, VC is regarded as an active, dynamic cell-mediated process, during which calcifying cell transition is critical. Mesenchymal stem cells (MSCs), with a multidirectional differentiation ability and great potential for clinical application, play a duplex role in the VC process. MSCs facilitate VC mainly through osteogenic transformation and apoptosis. Meanwhile, several studies have reported the protective role of MSCs. Anti-inflammation, blockade of the BMP2 signal, downregulation of the Wnt signal, and antiapoptosis through paracrine signaling are possible mechanisms. This review displays the evidence both on the facilitating role and on the protective role of MSCs, then discusses the key factors determining this divergence.

KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. The poor survival may be due to a high proportions of tumor recurrence and metastasis. Kinesin family member C1 (KIFC1) is highly expressed in a variety of neoplasms and is a potential marker for non-small cell lung cancer or ovarian adenocarcinoma metastasis. Nevertheless, the role of KIFC1 in HCC metastasis remains obscure. We investigated this in the present study using HCC cell lines and clinical specimens. Our results indicated that increased levels of KIFC1 were associated with poor prognosis and metastasis in HCC. In addition, KIFC1 induced epithelial-to-mesenchymal transition (EMT) and HCC metastasis both in vitro and in vivo. This tumorigenic effect depended on gankyrin; inhibiting gankyrin activity reversed EMT via activation of protein kinase B (AKT)/Twist family BHLH transcription factor 1 (AKT/TWIST1). We also found that KIFC1 was directly regulated by the microRNA miR-532-3p, whose downregulation was associated with metastatic progression in HCC. These results denote that a decrease in miR-532-3p levels results in increased KIFC1 expression in HCC, leading to metastasis via activation of the gankyrin/AKT/TWIST1 signaling pathway.