Predictors and clinical outcomes of permanent pacemaker implantation after transcatheter aortic valve implantation.

OBJECTIVE: This study aimed to identify the incidence, risk factors, and outcomes of permanent pacemaker (PPM) implantation after transcatheter aortic valve implantation (TAVI) procedures. METHODS: A retrospective analysis was conducted on 70 patients who underwent TAVI at the Department of Cardiology, Fujian Provincial Hospital, from January 2018 to March 2022. Based on whether a new PPM was implanted after TAVI, all patients were divided into two groups: NEW PPM and NO PPM. Baseline characteristics and clinical data were compared between the two groups. Univariate analysis was used to analyze different variables between the two groups. A binary logistic regression analysis was used to evaluate independent correlates for PPM implantation after TAVI. RESULTS: The mean age of the 70 patients was 73.1 ± 8.8 years. The incidence of PPM implantation was 17.1%. Patients with diabetes and chronic kidney disease were more likely to require PPM (50% vs. 20.7%, p = 0.042, 25% vs. 5.2%, p = 0.042). Our study did not identify any significant differences in the incidence of electrocardiographic conduction disturbances except for the previous right bundle branch block (RBBB) (NO PPM 6.9% vs. NEW PPM 33.3%, p < 0.05). We found that prosthesis size, implantation depth, procedural duration, and length of hospital and intensive care unit (ICU) stays were comparable between the two groups. The leading independent predictors of PPM implantation were previous RBBB (odds ratio 10.129, p = 0.034). CONCLUSION: The previous RBBB was the leading independent predictor of PPM implantation. New PPM was not associated with significantly new-onset left BBB, extended post-procedure hospitalization, ICU stay, or procedural duration.

Geriatric nutrition risk index in the prediction of all-cause and cardiovascular mortality in older adults with hyperlipidemia: NHANES 1999-2018.

BACKGROUND: Malnutrition is linked to a higher risk of unfavorable outcomes in various illnesses. The present investigation explored the correlation between inadequate nutritional condition and outcomes in older individuals diagnosed with hyperlipidemia. METHODS: The geriatric nutritional risk index (GNRI) was used to evaluate the nutritional status. All patients were divided into two groups according to GNRI. A Kaplan-Meier analysis was used to assess the survival rates of different groups at risk of malnutrition. In addition, GNRI was used in COX proportional risk regression models to evaluate its predictive effect on both overall mortality and cardiovascular mortality among patients with hyperlipidemia. Furthermore, the study employed restricted cubic splines (RCS) to examine the nonlinear correlation between GNRI and mortality. RESULTS: The study included 4,532 elderly individuals diagnosed with hyperlipidemia. During a median follow-up duration of 139 months, a total of 1498 deaths from all causes and 410 deaths from cardiovascular causes occurred. The Kaplan-Meier analysis demonstrated significantly poorer survival among individuals at risk of malnutrition, as indicated by the GNRI. In the malnutrition risk group, the modified COX proportional hazards model revealed that a decrease in GNRI was associated with a higher risk of all-cause mortality (HR=1.686, 95% CI 1.212-2.347) and cardiovascular mortality (HR=3.041, 95% CI 1.797-5.147). Furthermore, the restricted cubic splines revealed a non-linear association between GNRI and both all-cause mortality and cardiovascular mortality (p-value for non-linearity = 0.0039, p-value for non-linearity=0.0386). CONCLUSIONS: In older patients with hyperlipidemia, lower levels of GNRI are associated with mortality. The GNRI could potentially be used to predict all-cause mortality and cardiovascular mortality.

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.

LRP4 promotes proliferation, migration, and invasion in papillary thyroid cancer.

Dysregulation of cell proliferation and death is considered the foundation of the malignant biological characteristics of cancer. In this study, we conducted a comprehensive analysis of a massively parallel whole transcriptome resequencing of paired papillary thyroid cancer and normal thyroid tissues from 19 patients. In addition, we found that LRP4, a member of the low-density lipoprotein receptor-related protein family, is significantly overexpressed in thyroid carcinoma. We demonstrated through quantitative real-time polymerase chain reaction (qRT-PCR) that LRP4 is upregulated in papillary thyroid cancer (PTC) tissues. This observation was also consistent with data analyzed from The Cancer Genome Atlas (TCGA) cohort. Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target.

LncRNA CCND2-AS1 promotes proliferation, migration, and invasion in papillary thyroid carcinoma.

In decades, a lot of long non-coding RNAs (LncRNAs) have been proven to exert influences on tumorigenesis in vitro and in vivo. Many lncRNAs have been reported as effective therapeutic targets and biomarkers in various cancers. However, whether LncRNAs are associated with the progression of PTC remains largely unknown. In this study, we measured the expression of CCND2-AS1 in PTC cell lines by quantitative real-time polymerase chain reaction (qRT-PCR).We found that CCND2-AS1 expression was significantly over-expressed in PTC cell lines compared to normal thyroid epithelial cells. Gain-and loss-of-function experiments were performed to investigate the role of CCND2-AS1 in PTC cells. In vitro experiments, we proved that CCND2-AS1 knockdown in TPC1 significantly suppressed cell proliferation, migration, and invasion, while CCND2-AS1 overexpression in BCPAP had the opposite effects. Meanwhile, we also found that CCND2-AS1 could regulate N-cadherin and Vimentin expression, which may influence invasion and migration. Our findings indicate that the lncRNA CCND2-AS1 is a gene associated with PTC and might become a potential therapeutic target.

Predictive Factors of Skip Metastasis in Papillary Thyroid Cancer.

BACKGROUND Skip metastasis is defined as metastasis incident to the lateral compartment without involvement of the central compartment, and is generally unpredictable in papillary thyroid cancer (PTC). The present study aimed to investigate the frequency and predictor value of skip metastasis in PTC patients. MATERIAL AND METHODS A total of 355 patients diagnosed with thyroid cancer who had received a prior complete thyroidectomy with bilateral central neck and ipsilateral lateral neck lymph node dissection were enrolled in this study. The clinicopathological and ultrasound features were analyzed. A univariate and multivariate analysis were performed to identify the risk factors of skip metastasis. RESULTS The frequency of skip metastasis was 12.4% (44/355). The PTC patients with skip metastasis exhibited fewer lymph node metastasis, which was more commonly detected in tumor size ≤1 cm (OR 9.354; p=0.001; 95% confidence interval (CI) 1.865-26.735), tumors located in upper pole (OR 3.822; p<0.001; 95% CI 1.935-7.549), without a well-defined margin (OR 2.528; p=0.016; CI 1.191-5.367), and extrathyroidal extension (OR 2.406; p=0.013; CI 1.691-4.367). CONCLUSIONS Skip metastasis was common in PTC. The PTC patients with a tumor size ≤1.0 cm, located in the upper pole, without a well-defined margin and extrathyroidal extension should be carefully evaluated for skip metastasis.

Purification and characterization of a novel cell-penetrating carrier similar to cholera toxin chimeric protein.

Developing a recombinant vector for noninvasively delivering biological macromolecules into the brain is important. This study constructed and purified a protein complex based on the cholera toxin (CT) molecular structure. Enhanced green fluorescent protein (EGFP)-modified A2 subunits of CT (CTA2) were used as tracer molecules for introduction of transactivator of transcription (TAT) through the A subunit into cells. The protein complex EGFP-CTA2-TAT/(CTB)5 (CTB: B subunit of CT) was obtained using an in vitro recombination method and verified by monosialoganglioside-enzyme-linked immunosorbent assay and high performance liquid chromatography assay. The protein complexes bound more strongly to monosialoganglioside (GM1) than (CTB)5 at low concentrations (0.625-1.25 µg/mL). In vitro assays revealed that the transmembrane function of TAT was also maintained. The GM1-binding activity and cell membrane-penetrating ability suggested that a CT structure-based protein complexes could be used to design a delivery carrier for intranasal administration through GM1 binding. The expression vector introduced in this study provides a feasible expression frame for constructing several new macromolecular protein drugs for effective cell penetration.

[Study on quality evaluation of Dafo Longjing tea based on near infrared spectroscopy].

Seven quantitative analysis models for Dafo Longjing tea, including tea color, liquor color, aroma, taste, infused leaf, total points of five factors and total points of six factors, were built by applying near infrared spectroscopy combined with partial least squares (NIRS-PLS), in order to find a objective and scientific method for tea quality evaluation. Results showed that both the calibration samples and the prediction samples of the seven models had acquired a high fitting degree when the number of principal components was below 10, and the value of Rc, RMSEC, Rp and RMSEP were between 90.48%-98.43%, 1.14%-2.09%, 90.00%-96.65%, and 1.52% 2.84%, respectively. Among them, the total points of five factors model had the best prediction performance, and the value of Rp and RMSEP was 96.65% and 1.52%, respectively. Moreover, it was also found that the prediction precision of total points models were higher than that of single factor ones. It seems that the quality evaluation of Dafo Longjing tea could be realized by using NIRS-PLS to some extent.

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.].

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.

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.

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.

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.

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.

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.

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.

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.