Minimally invasive repair of iatrogenic right ventricular perforation guided by bedside contrast-enhanced ultrasound: A case report and literature review.

This case report involves a 93-year-old female patient with atrioventricular block and suffered right ventricular free wall perforation during installation of Micra Leadless Pacemaker (MLP). Pericardial tamponade occurred shortly, and we adopted pericardial catheter drainage as the primary emergency treatment. Considering the patient's physical conditions and leveraging the special treatment facilitates of the Intensive Care Unit (ICU), we tried a new emergency treatment approach. After putting the patient under intravenous anesthesia (no cardiac arrest), we made a small intercostal incision and performed bedside minimally invasive repair of right ventricular free wall perforation. It should be noted that ultrasound played a key role in pinpointing the breach and intraoperative guidance. We first used contrast-enhanced ultrasound (CEUS) to locate the breach. Then guided by bedside ultrasound, we accessed the perforation with the minimum incision size (5 cm). Our experience in this case may serve as a good reference in the emergency treatment for right ventricular free wall perforation.

Response of distribution patterns of two closely related species in Taxus genus to climate change since last inter-glacial.

Climate change affects the species spatio-temporal distribution deeply. However, how climate affects the spatio-temporal distribution pattern of related species on the large scale remains largely unclear. Here, we selected two closely related species in Taxus genus Taxus chinensis and Taxus mairei to explore their distribution pattern. Four environmental variables were employed to simulate the distribution patterns using the optimized Maxent model. The results showed that the highly suitable area of T. chinensis and T. mairei in current period was 1.616 × 105 km2 and 3.093 × 105 km2, respectively. The distribution area of T. chinensis was smaller than that of T. mairei in different periods. Comparison of different periods shown that the distribution area of the two species was almost in stasis from LIG to the future periods. Temperature and precipitation were the main climate factors that determined the potential distribution of the two species. The centroids of T. chinensis and T. mairei were in Sichuan and Hunan provinces in current period, respectively. In the future, the centroid migration direction of the two species would shift towards northeast. Our results revealed that the average elevation distribution of T. chinensis was higher than that of T. mairei. This study sheds new insights into the habitat preference and limiting environment factors of the two related species and provides a valuable reference for the conservation of these two threatened species.

SPTBN2 Promotes the Progression of Thyroid Cancer by Accelerating G1/S Transition and Inhibiting Apoptosis.

Background: Thyroid carcinoma (TC) is an increasingly common malignancy of endocrine organs, and its most frequently encountered histotype is papillary thyroid cancer (PTC). Identifying new potential gene alterations is important for completely elucidating the mechanism of PTC initiation and progression. Thus, we performed whole transcriptome sequence analysis (RNA-seq) on 79 PTC tissue samples and paired adjacent nontumor tissue samples to study the molecular mechanism of TC tumorigenesis and progression further. The results of RNA-seq analysis showed that spectrin beta, nonerythrocytic 2 (SPTBN2), was markedly overexpressed in PTC tissues relative to that in the paired nontumor tissues. Additionally, the analysis results for 502 PTC samples and 58 nontumor thyroid samples from The Cancer Genome Atlas dataset were consistent with our RNA-seq results. However, the molecular mechanisms and function of SPTBN2 in TC progression remain unknown. Methods: We examined SPTBN2 gene expression in 48 papillary thyroid tumor tissues and paired adjacent normal thyroid tissues by using qRT-PCR. SPTBN2 expression in the TC cell lines was silenced by small interfering RNA. Then, the transfected TC cells were used to investigate the in vitro function of SPTBN2. Result: The expression of SPTBN2 was significantly upregulated in our RNA-seq cohort, our local validated cohort, and TCGA RNA-seq cohort. The results of the in vitro experiment revealed that in TC cell lines, SPTBN2 downregulation considerably suppressed tumor cell proliferation, the cell cycle, migration, colony formation, and invasion and induced cell apoptosis. Furthermore, the protein levels of CCNE2, CDK2, CDK4, and Bcl-2 were downregulated, and those of P21, Bax, cleaved caspase-8, and cleaved caspase-3 had increased in transfected TC cells relative to in control TC cells. Conclusion: The downregulation of SPTBN2 caused apoptosis and retarded G1/S cell cycle transition in TC cells. Thus, SPTBN2 may be a good candidate gene for TC diagnosis and therapy.

Erratum: Long non-coding RNA LINC00673 promotes breast cancer proliferation and metastasis through regulating B7-H6 and epithelial-mesenchymal transition.

[This corrects the article on p. 1273 in vol. 8, PMID: 30094100.].

Knockdown of LncRNA MALAT1 Alleviates Coxsackievirus B3-Induced Acute Viral Myocarditis in Mice via Inhibiting Th17 Cells Differentiation.

Acute viral myocarditis (AVMC), most often caused by coxsackievirus B3 (CVB3) infection, is characterized by myocardial inflammation associated with high morbidity and mortality. A pathogenic role for T helper (Th) 17 cells in AVMC is well established. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to play a key role in various inflammatory diseases. However, the expression of MALAT1 and its impact on Th17 cells differentiation in AVMC remain unclear. In the present study, we found that MALAT1 was highly expressed in mice with AVMC, and the expression was correlated positively with cardiac pathological scores, cardiac IL-17 mRNA expression, and the percentages of splenic Th17 cells. We further demonstrated that MALAT1 knockdown could significantly alleviate the severity of disease and inhibit the differentiation of Th17 cells, accompanying the reduced mRNA expression of RORγt and productions of Th17-related pro-inflammatory cytokines in vivo. Additionally, in vitro analysis showed that MALAT1 knockdown suppressed naïve CD4+ T cells differentiation towards Th17 cells. In conclusion, our results suggest that MALAT1 knockdown alleviates CVB3-induced AVMC in mice, which may be partially attributable to the decline in Th17 cells responses. MALAT1 may serve as a novel therapeutic option in AVMC.

Effect of red light on the composition of metabolites in tea leaves during the withering process using untargeted metabolomics.

BACKGROUND: Red light withering significantly improves the sensory flavor qualities of tea, although changes in metabolites during this process have not been systematically studied until now. The present study comprehensively analyzes metabolites in withered tea leaves at 2-h intervals up to 12 h under red light (630 nm) and dark conditions using ultra performance liquid chromatography-high resolution mass spectrometry (untargeted metabolomics). RESULTS: Ninety-four non-volatile compounds are identified and relatively quantified, including amino acids, catechins, dimeric catechins, flavonol glycosides, glycosidically-bound volatiles, phenolic acids and nucleosides. The results show that amino acids, catechins and dimeric catechins are most affected by red light treatment. Ten free amino acids, theaflavins and theasinensin A increase after red light irradiation, whereas epigallocatechin gallate and catechin fall. CONCLUSION: The present study provides a comprehensive and systematic profile of the dynamic effects of red light on withering tea and a rationale for its use in tea processing quality control. © 2021 Society of Chemical Industry.

Effect of increased positive end-expiratory pressure on intracranial pressure and cerebral oxygenation: impact of respiratory mechanics and hypovolemia.

BACKGROUND: To evaluate the impact of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) in animals with different respiratory mechanics, baseline ICP and volume status. METHODS: A total of 50 male adult Bama miniature pigs were involved in four different protocols (n = 20, 12, 12, and 6, respectively). Under the monitoring of ICP, brain tissue oxygen tension and hemodynamical parameters, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O. Measurements were taken in pigs with normal ICP and normovolemia (Series I), or with intracranial hypertension (via inflating intracranial balloon catheter) and normovolemia (Series II), or with intracranial hypertension and hypovolemia (via exsanguination) (Series III). Pigs randomized to the control group received only hydrochloride instillation while the intervention group received additional chest wall strapping. Common carotid arterial blood flow before and after exsanguination at each PEEP level was measured in pigs with intracranial hypertension and chest wall strapping (Series IV). RESULTS: ICP was elevated by increased PEEP in both normal ICP and intracranial hypertension conditions in animals with normal blood volume, while resulted in decreased ICP with PEEP increments in animals with hypovolemia. Increasing PEEP resulted in a decrease in brain tissue oxygen tension in both normovolemic and hypovolemic conditions. The impacts of PEEP on hemodynamical parameters, ICP and brain tissue oxygen tension became more evident with increased chest wall elastance. Compare to normovolemic condition, common carotid arterial blood flow was further lowered when PEEP was raised in the condition of hypovolemia. CONCLUSIONS: The impacts of PEEP on ICP and cerebral oxygenation are determined by both volume status and respiratory mechanics. Potential conditions that may increase chest wall elastance should also be ruled out to avoid the deleterious effects of PEEP.

Performance of Lactate and CO2-Derived Parameters in Predicting Major Postoperative Complications After Cardiac Surgery With Cardiopulmonary Bypass: Protocol of a Diagnostic Accuracy Study.

Background: CO2-derived parameters are increasingly used to identify either low-flow status or anaerobic metabolism in shock resuscitation. However, the performance of CO2-derived parameters in cardiac surgical patients is poorly understood. This study aims to compare the performance of lactate and CO2-derived parameters in predicting major postoperative complications after cardiac surgery with cardiopulmonary bypass. Methods: This is a prospective, single-center, diagnostic accuracy study. All patients who receive elective cardiac surgery involving cardiopulmonary bypass will be screened for study eligibility. Blood samples will be taken for the calculation of CO2-derived parameters, including the venous-arterial difference in CO2 partial pressure (PCO2 gap), venous-arterial difference in CO2 content to arterial-venous O2 content ratio (Cv-aCO2/Ca-vO2), and venous-arterial difference in CO2 partial pressure to arterial-venous O2 content ratio (Pv-aCO2/Ca-vO2) at ICU admission, and 3, 6, and 12 h later. Baseline, perioperative data will be collected daily for 7 days; patients will be followed up for 28 days to collect outcome data. The primary endpoint is the occurrence of major postoperative complications. Receiver-operating characteristics (ROC) curve analysis will be carried out to assess the predictive performance of lactate and CO2-derived parameters. The performance of the ROC curves will be compared. Discussion: The performance of lactate and CO2-derived parameters in predicting major postoperative complications will be investigated in the non-sepsis population, which has not been extensively investigated. Our study will compare the two surrogates of respiratory quotient directly, which is an important strength. Trial Registration: ChiCTR, ChiCTR2000029365. Registered January 26th, 2020, http://www.chictr.org.cn/showproj.aspx?proj=48744.

[Study of multimodal monitoring in neurocritical care patients].

OBJECTIVE: To explore the significance of multimodal monitoring in the monitoring and treatment of neurocritical care patients. METHODS: 104 neurocritical care patients admitted to the department of Critical Care Medicine of Fujian Provincial Hospital from March 2019 to January 2020 were enrolled. Patients were randomly assigned into two groups, with 52 in each group. In the routine monitoring treatment group, heart rate, blood pressure, respiratory rate and the changes in consciousness and pupils were monitored after operation. The patients were treated with routine medicine to reduce intracranial pressure (ICP), maintain proper cerebral perfusion pressure (CPP), balance fluid intake and output, and maintain the airway clear. Patients in the multimodal monitoring treatment group were treated with invasive ICP monitoring, ultrasound to assess brain structure, ultrasound to measure optic nerve sheath diameter (ONSD), transcranial color doppler (TCCD), internal jugular venous blood oxygen saturation monitoring, near-infrared spectroscopy (NIRS), non-invasive cerebral blood oxygen saturation monitoring and quantitative electroencephalogram monitoring. According to the monitoring results, the patients were given targeted treatment with the goal of controlling ICP and improving brain metabolism. The length of intensive care unit (ICU) stay, the incidences of neurological complications (secondary cerebral infarction, cerebral hemorrhage, high intracranial pressure, etc.), and the incidences of poor prognosis [6 months after the onset of Glasgow outcome score (GOS) 1 to 3] were compared between the two groups. Spearman rank correlation analysis of the correlation between invasive ICP and the ICP value which was calculated by TCCD. The receiver operating characteristic (ROC) curve of invasive ICP and pulsatility index of middle cerebral artery (PIMCA) were used to predict poor prognosis. RESULTS: The length of ICU stay in the multimodal monitoring treatment group was significantly shorter than that of the routine monitoring treatment group (days: 6.27±3.81 vs. 9.61±5.09, P < 0.01), and the incidence of neurological complications was significantly lower than that in the routine monitoring treatment group (9.62% vs. 25.00%, P < 0.05). In the multimodal monitoring treatment group, 37 cases had a good prognosis and 15 cases had a poor prognosis, while the routine monitoring treatment group had a good prognosis in 27 cases and a poor prognosis in 25 cases. The incidence of poor prognosis in the multimodal monitoring treatment group was lower than that of the routine monitoring treatment group (28.85% vs. 48.08%, P < 0.05). In the multimodal monitoring treatment group, the invasive ICP and PIMCA of patients with good prognosis were significantly lower than those of patients with poor prognosis [invasive ICP (mmHg, 1 mmHg = 0.133 kPa): 16 (12, 17) vs. 22 (20, 24), PIMCA: 0.90±0.33 vs. 1.39±0.58, both P < 0.01]. There was no significant difference in resistance index of the middle cerebral artery (RIMCA) between the good prognosis group and the poor prognosis group (0.63±0.12 vs. 0.66±0.15, P > 0.05). There was a positive correlation between the invasive ICP and the ICP value which was calculated by TCCD (r = 0.767, P < 0.001). ROC curve analysis showed that the area under ROC curve (AUC) of invasive ICP for poor prognosis prediction was 0.906, the best cut-off value was ≥ 18 mmHg, the sensitivity was 86.49%, and the specificity was 86.67%. The AUC of PIMCA for poor prognosis prediction was 0.759, the best cut-off value was ≥ 1.12, the sensitivity was 81.08%, and the specificity was 60.00%. The AUC of invasive ICP was greater than PIMCA (Z = 2.279, P = 0.023). CONCLUSIONS: Comprehensive analysis of multimodal monitoring indicators for neurocritical care patients to guide clinical treatment can reduce the length of hospital stay, and reduce the risk of neurosurgery complications and disability; invasive ICP can predict poor prognosis of neurocritical care patients.

Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma.

Purpose: Aldo-keto reductase family 1, member C2 (AKR1C2) gene encodes for a member of the AKR superfamily and participates in the metabolism of various drugs. Moreover, tumor and normal tissues exhibit an evident difference in the expression level of this gene. Methods: We downloaded and analyzed AKR1C2 expression level and the data consisting of the clinicopathological features of 490 papillary thyroid carcinoma (PTC) tumor tissues and 59 normal thyroid tissues from The Cancer Genome Atlas (TCGA) cohort. Diverse statistical methods, such Chi-square test, univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curves were used. We down-/up-regulated the expression of AKR1C2 and explored its specific role in thyroid cancer cell lines by utilizing the si-RNA and plasmid. Results: We divided all patients who were collected in TCGA data sets into under-expressed (n = 245) and over-expressed groups (n = 245). We subsequently analyzed the data and obtained the following findings: (a) AKR1C2 is down-regulated in papillary thyroid carcinoma (PTC) (p<0.001), (b) Kaplan-Meier result revealed that high expression level of AKR1C2 are correlated with favorable survival in PTC (p = 0.043), and (c) factors independently associated with recurrence-free survival are AKR1C2 expression (hazard ratio (HR 0.819) and American Joint Committee on Cancer (AJCC) stage (HR 1.534). We also analysed the relationship between AKR1C2 expression and clinicopathological features in the validated cohort. AKR12C under-expression correlated with lymph node metastasis (p = 0.009) and AJCC stage (p= 0.001) which might indicate AKR12C as a prognostic factor in PTC. The cell line experiment results showed that the knockdown and overexpression of AKR1C2 significantly enhance and weaken the abilities of migration and invasion in papillary thyroid carcinoma cell. Conclusion: Our results indicated that AKR1C2 exerts inhibitory effects on PTC oncogenesis and elevated AKR1C2 expression is associated with the favorable prognostic factors and recurrence free survival.

NECTIN4 promotes papillary thyroid cancer cell proliferation, migration, and invasion and triggers EMT by activating AKT.

Papillary thyroid cancer (PTC) is the most frequent type of malignant thyroid cancer, but its molecular mechanisms remain unknown. To better understand the tumorigenesis and progression of PTC, we conducted a comprehensive analysis of the whole-transcriptome resequencing of paired PTC and normal thyroid tissues. Nectin cell adhesion molecule 4 (NECTIN4) was significantly overexpressed in thyroid carcinoma compared with that in matched normal tissue. We also assessed the relation between the expression level of NECTIN4 and the clinicopathological features of PTC in The Cancer Genome Atlas database, and results showed that upregulated NECTIN4 is associated with lymph node metastasis (P<0.001) and tumor size (P=0.017). The biological function of NECTIN4 was also investigated by using the PTC cell lines TPC-1 and KTC-1. In vitro experiments demonstrated that NECTIN4 downregulation significantly inhibits the colony formation, proliferation, migration, and invasion of PTC cell lines. NECTIN4 could modulate the expression of epithelial-mesenchymal transition-related proteins via the PI3K/AKT pathway, and SC79, an AKT phosphorylation activator, could reverse the si-RNA knockdown effect. In addition, after the use of AKT inhibitors (LY 294,002), we found that SiRNA have similar effect with AKT inhibitors. Taking the results together, the current study shows that NECTIN4 has important biological implications in the tumorigenesis and metastasis of PTC and may be a potential therapeutic target for the disease.

Lipase member H is a downstream molecular target of hypoxia inducible factor-1α and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. MATERIALS AND METHODS: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. RESULTS: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial-mesenchymal transition pathway in PTC. CONCLUSION: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future.

LncRNA MVIH knockdown inhibits the malignancy progression through downregulating miR-505 mediated HMGB1 and CCNE2 in acute myeloid leukemia.

BACKGROUND: This study aimed to investigate the regulatory role of long non-coding RNA associated with microvascular invasion in hepatocellular carcinoma (lnc-MVIH) in the progression of acute myeloid leukemia (AML) and the underlying mechanism. METHODS: Lnc-MVIH expression was detected in AML cell lines AML-193, KG-1, HL-60, OCI-AML2 and primary normal bone marrow mononuclear cells (BMMC). The effect of lnc-MVIH knockdown on cell proliferation, apoptosis and miR-505 expression were detected by transfection of lnc-MVIH shRNA and control shRNA into KG-1 cells. And the effect of miR-505 knockdown on lnc-MVIH, cell proliferation, cell apoptosis as well as potential miR-505 target genes [high mobility group box 1 (HMGB1) and cyclin E2 (CCNE2)] in lnc-MVIH knockdown treated KG-1 cells was assessed by transfection of lnc-MVIH shRNA and lnc-MVIH shRNA & miR-505 shRNA into KG-1 cells. RESULTS: Lnc-MVIH expression was elevated in AML-193, KG-1, OCI-AML2 cell lines, but similar in HL-60 cell line compared with primary normal BMMC. Lnc-MVIH knockdown inhibited cell proliferation but promoted cell apoptosis in KG-1 cells, meanwhile miR-505 expression was increased by lnc-MVIH knockdown in KG-1 cells. And in rescue experiments, miR-505 knockdown had no effect on expression of lnc-MVIH, while it increased the expressions of HMGB1 and CCNE2, promoted cell proliferation, inhibited cell apoptosis in lnc-MVIH knockdown treated KG-1 cells. CONCLUSIONS: Lnc-MVIH knockdown inhibits cell proliferation but promotes cell apoptosis via regulating miR-505 mediated HMGB1 and CCNE2 in AML.

CLDN10 is Associated with Papillary Thyroid Cancer Progression.

The incidence of thyroid cancer is staying at a high level. Claudin family is a skelemin contacting with the intercellular junction and can keep a dynamic balance between cells. Recently, many types of research indicated that the expression level of claudins is closely related to various cancer types and they can be novel diagnostic markers. For instance, Claudin-10(CLDN10) is the high expression in primary hepatocellular carcinoma, papillary thyroid cancer (PTC) and so on. But the biological role and function of CLDN10 in PTC are unclear. In our study, we measured the expression of CLDN10 in human normal tissues and matched PTC tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and this observation was consistent with that in the TCGA cohort. We discovered that high expression of CLDN10 was correlated with lymph node metastasis, age and Histological type in TCGA cohorts. Kaplan-Meier analysis showed that patients with higher CLDN10 expression had a worse overall survival. In vitro, CLDN10 could promote cellular proliferation, migration, and invasion in PTC cell lines. In a word, CLDN10 is a functionally gene facilitating tumorgenesis in PTC and acts as an oncogene in PTC.

Efficacy of common salvage chemotherapy regimens in patients with refractory or relapsed acute myeloid leukemia: A retrospective cohort study.

To assess treatment response and overall survival (OS) in refractory or relapsed acute myeloid leukemia (R/R AML) patients treated by different common salvage chemotherapy regimens.Medical records data from 142 R/R AML patients were reviewed in this retrospective study. Patients were treated with regimens based on the following drugs: cytarabine, granulocyte colony-stimulating factor (G-CSF), and fludarabine (FLAG) (n = 46); cytarabine and G-CSF in addition to aclarubicin or daunorubicin (CAG/DAG) (n = 30); cytarabine, G-CSF, and cladribine (CLAG) (n = 27); cytarabine, etoposide, and mitoxantrone (MEA) (n = 17); cytarabine plus idarubicin, daunorubicin, or mitoxantrone (IA/DA/MA) (n = 12); and homoharringtonine, cytarabine, and aclarubicin or daunorubicin (HAA/HAD) (n = 10).A total of 43 (35.2%) patients achieved complete remission (CR), 60 (49.2%) patients achieved overall remission rate (ORR), and 18 (14.8%) patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR. Median OS was 8.0 (95% CI 6.6-9.4) months with a 1-year OS rate of (29.9 ±â€Š3.9)% and 3-year OS rate of (11.1 ±â€Š3.6)%. No difference of CR (P = .621), ORR (P = .385), and allo-HSCT (P = .537) achievement was observed among different chemotherapy regimens. Interestingly, we observed that the CLAG-based regimen did not affect CR (P = .165), while it achieved a numerically higher ORR (P = .093) and was an independent factor for prolonged OS (P = .016). No other regimens were determined to be correlated with CR, ORR, or OS.FLAG-, CAG/DAG-, CLAG-, MEA-, IA/DA/MA- and HAA/HAD-based regimens were found to achieve similar CR rates, while the CLAG-based regimen achieved numerically higher ORR rates and significant favorable OS. Therefore, CLAG-based regimens should be a prioritized treatment option for R/R AML patients.

Prediction of central lymph node metastasis in papillary thyroid microcarcinoma according to clinicopathologic factors and thyroid nodule sonographic features: a case-control study.

BACKGROUND: Preoperative diagnosis of central lymph node metastasis (CLNM) poses to be a challenge in clinical node-negative papillary thyroid microcarcinoma (PTMC). This research work aims at investigating the association existing between BRAF mutation, clinicopathological factors, ultrasound characteristics, and CLNM, in addition to establishing a predictive model for CLNM in PTMC. MATERIALS AND METHODS: The study included 673 PTMC patients, already undergone total thyroidectomy or lobectomy with prophylactic central lymph node dissection. The predictor factors were identified through univariate and multivariate analyses. The support vector machine was put to use to develop statistical models, which could predict CLNM on the basis of independent predictors. RESULTS: Tumor size (>5 mm), lower location, no well-defined margin, contact of >25% with the adjacent capsule, display of enlarged lymph nodes, and BRAF mutation were independent predictors of CLNM. Through the use of the predictive model, 79.6% of the patients were classified accurately, the sensitivity and specificity amounted to be 85.1% and 75.8%, respectively, and the positive predictive value and negative predictive value stood at 71.6% and 87.6%, respectively. CONCLUSIONS: We established a predictive model in order to predict CLNM preoperatively in PTMC when preoperative diagnosis of CLNM was not clear.

TEKT4 Promotes Papillary Thyroid Cancer Cell Proliferation, Colony Formation, and Metastasis through Activating PI3K/Akt Pathway.

Thyroid carcinoma is the most common malignancy of the endocrine system worldwide, but its molecular mechanisms remain unclear. Some diseases are associated with TEKT4 gene. However, its role in thyroid carcinoma has yet to be fully examined. This study was designed to investigate the function of TEKT4 in papillary thyroid cancer (PTC). The effect of TEKT4 on aggressive behavior of PTC cell lines, namely, TPC1 and BCPAP, transfected with small interfering RNA was identified through cell proliferation, colony formation, migration, and invasion. Our previous study revealed that TEKT4 may be vital in PTC. In in vitro experiments, TEKT4 downregulation suppressed cell proliferation, colony formation, cell migration, and invasion. Our data also indicated that tumor-suppressing role of TEKT4 knockdown in PTC cell lines was associated with the silence of the PI3K/Akt pathway. Our study revealed that TEKT4 shows important biological implications and is worthy of further study.

Long non-coding RNA LINC00673 promotes breast cancer proliferation and metastasis through regulating B7-H6 and epithelial-mesenchymal transition.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been reported as key regulators of tumor progression in recent decades. However, the potential molecular mechanisms of breast cancer are still unclear. With the development of sequencing technology, we discovered that LINC00673 is upregulated in tumor tissues. But the main role of LINC00673 in breast cancer has yet to be confirmed. MATERIALS AND METHODS: 35 pairs of breast tumors and normal tissues were selected to real-time quantitative polymerase chain reaction (RT-qPCR) to validate LINC00673 is overexpressed in tumor tissues. We conducted proliferation, colony formation, migration, invasion assays, and EMT-related phenotype to determine the specific role of LINC00673 in breast cancer cell lines (MDA-MB-231, BT-549, and MCF-7) transfected with small interfering RNA. Gene expression profiling was conducted to found LINC00673-associated gene transcriptional changes. RESULTS: We discovered that LINC00673 is significantly upregulated in breast cancer tissues compared to paired adjacent non-tumor tissues by RT-qPCR and highly expressed LINC00673 is positively correlated with lymph node metastasis and clinical stage in the validated cohort. Knocking down LINC00673 inhibited cell proliferation and metastasis, whereas upregulated LINC00673 had the opposite effect. Gene expression profiling results indicated that LINC00673 could influence NCR3LG1(B7-H6) expression in transcriptional level. Western Blot showed us that LINC00673 could regulate epithelial-mesenchymal transition (EMT) and B7-H6 in protein level. Then we demonstrated that knocking down B7-H6 could decrease breast cancer cell proliferation and metastasis. CONCLUSION: In this study, we identified the role of LINC00673 in inducing proliferation and metastasis of breast cancer cell lines and it might act as an underlying therapeutic target for breast cancer.

lncRNA LINC00673 induces proliferation, metastasis and epithelial-mesenchymal transition in thyroid carcinoma via Kruppel-like factor 2.

The incidence of thyroid cancer has increased in the past decades; however, the underlying molecular mechanisms of thyroid cancer tumorigenesis remain unknown. Using sequencing technology, long intergenic non­protein coding RNA 673 (LINC00673) was identified to be upregulated in several tumor tissues. However, the biological role of LINC00673 in thyroid carcinoma has yet to be determined. In this study, 60 matched pairs of thyroid tumor tissue and normal tissue were selected for study using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate previous findings; then, clinicopathologic features of the tissues were analyzed. Proliferation, colony formation, migration and invasion assays were performed, and epithelial-mesenchymal transition (EMT)-associated phenotypes were investigated following transfection with small interfering RNA to determine the specific role of LINC00673 in thyroid carcinoma cell lines (TPC1, KTC­1 and BCPAP). The study revealed that long non­coding RNA LINC00673 was significantly upregulated in thyroid cancer tissues compared with paired adjacent non­tumor tissues using RT-qPCR and that high expression of LINC00673 is was associated with larger tumor size and lymph node metastasis in the validated cohort. Knockdown of LINC00673 inhibited cell proliferation and metastasis, whereas, LINC00673 overexpression had the opposite effect. The results showed that LINC00673 may influence EMT and the expression of Kruppel-like factor 2 (KLF2). Notably, KLF2 is considered a tumor suppressor gene in a variety of tumors. Finally, knock down of KLF2 enhanced thyroid carcinoma cell proliferation, and invasion and migration. In this study, the function of LINC00673 in promoting the proliferation and metastasis of thyroid carcinoma cell lines was identified, and LINC00673 may act as a novel therapeutic target for treating thyroid carcinoma.

Synaptopodin-2 plays an important role in the metastasis of breast cancer via PI3K/Akt/mTOR pathway.

INTRODUCTION: Synaptopodin 2 (SYNPO2) is a functioning protein. It has been detected in many malignancies. But the relation between SYNPO2 and breast cancer (BC) is unclear. MATERIALS AND METHODS: In this study, we explored the expression and function of SYNPO2 in BC. We found that SYNPO2 gene in BC was downregulated at the transcriptional level in both validated and TCGA cohorts. RESULTS: The results revealed that age, lymph node metastasis, and clinical stage in the validated cohort were related to the expression of SYNPO2 negatively. Kaplan-Meier analysis showed that patients with lower SYNPO2 expression had a worse overall survival. DISCUSSION: We found that migration and invasion were promoted after knocking down SYNPO2 in MCF-7, MDA-MB-231, BT-549, and MDA-MB-468. Meanwhile, knockdown of SYNPO2 could enhance PI3K/AKT/mTOR signaling pathway, which may induce migration and invasion. Our findings reveal that SYNPO2 was associated with BC.