LHX2 Is a Potential Biomarker and Associated with Immune Infiltration in Breast Cancer.

Worldwide, breast cancer is the most common malignancy. LHX2, a member of the LIM homeobox gene family and a transcription factor, plays a crucial role in numerous tumors, but the function of LHX2 in breast cancer progression remains unknown. In this study, we show that LHX2 is upregulated in breast cancer tissues and positively correlated with breast cancer progression. Meanwhile, the clinical characteristics of breast cancer and LHX2 expression showed a strong correlation. GSEA showed that a high LHX2 expression may activate the T-cell activation pathway, PI3K/AKT/mTOR signaling pathway, and apoptosis pathway. Moreover, ssGSEA showed that Th1 cells and Th2 cells had a positive correlation with LHX2 expression in breast cancer. Experiments showed that LHX2 promotes the proliferation, colony formation, migration, and invasion of breast cancer cells. Immunohistochemistry and immunofluorescence assays helped to analyze LHX2-associated immune infiltration in breast cancer. A Western blot assay proved that LHX2 activated the PI3K/AKT/mTOR pathway and the apoptosis pathway. A TUNEL assay confirmed that LHX2 inhibited apoptosis. Taken together, LHX2 plays a vital role in breast cancer's progression and prognosis and could be an immune infiltration biomarker for breast cancer, and LHX2 activates the PI3K/AKT/mTOR pathway and apoptosis pathway in breast cancer.

NPM3 as a novel oncogenic factor and poor prognostic marker contributes to cell proliferation and migration in lung adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide, and despite recent advances in targeted therapies and immunotherapies, the clinical benefit remains limited. Therefore, there is an urgent need to further investigate the molecular mechanisms underlying lung cancer. The aim of this study was to investigate the expression and function of NPM3 in the tumor microenvironment of lung adenocarcinoma (LUAD). METHODS: We utilized bioinformatics tools and databases, including UALCAN, GEPIA2, HPA, and Sangerbox, to analyze NPM3 expression in LUAD samples and its association with prognosis and mutational landscape. NPM3 expression in various cell types was assessed at the single cell level using the TISCH database. We also used algorithms such as TIMER and EPIC to explore the crosstalk between NPM3 expression and immune features. KEGG enrichment analysis was performed to identify potential signaling pathways of NPM3. Finally, we employed siRNA knockdown strategy to investigate the effect of NPM3 on LUAD cell proliferation and migration in vitro. RESULTS: NPM3 was significantly upregulated in LUAD tissues and was strongly associated with poor prognosis and TP53 gene mutations. Single-cell sequencing analysis revealed that NPM3 was expressed in immune cells (dendritic cells and monocytes/macrophages) in the tumor microenvironment. Moreover, NPM3 expression was negatively associated with immune B cell and CD4 T cell infiltration, as well as with several immune-related genes (including CCL22, CXCR2, CX3CR1, CCR6, HLA-DOA, HLA-DQA2). KEGG enrichment analysis indicated that NPM3 expression was associated with cell cycle, CAMs, and NSCLC pathway genes. Finally, in vitro experiments showed that NPM3 knockdown inhibited LUAD cell proliferation and migration in NCI-H1299 and SPC-A1 cells, and suppressed the expression of CCNA2 and MAD2L1. CONCLUSION: Elevated NPM3 expression predicts poor clinical outcome and an immunosuppressive microenvironment in LUAD tissues. NPM3 promotes LUAD progression by promoting cell proliferation and migration, and targeting NPM3 may represent a novel therapeutic strategy for LUAD.

Neuroendocrine neoplasm with metastasis to the thyroid: a case report and literature review.

Thyroid cancer can be divided into two types according to its cellular origin, i.e., malignant tumors originating from thyroid cells and cancers that metastasize to the thyroid from other sites, the latter of which are, clinically rare. This article reports the diagnosis and treatment of a rectal neuroendocrine neoplasm metastasis to the thyroid. No similar cases have been reported before. This case suggests that when evaluating thyroid tumors, clinicians should not only carefully identify the clinical features of the tumor but also pay special attention to the patient's history of tumors, especially neuroendocrine neoplasms. For definite secondary thyroid malignancies, neck surgery is feasible if the thyroid is the only site of metastasis; otherwise, the subsequent diagnosis and treatment plan should be determined after a comprehensive evaluation of the primary tumor and patient's general condition.

A multidimensional pan-cancer analysis of DCAF13 and its protumorigenic effect in lung adenocarcinoma.

DCAF13 is a substrate recognition protein in the ubiquitin-proteasome system with oncogenic effects in several malignant tumors. However, it is unclear that the relationship between DCAF13 expression pattern and prognosis across different cancer types. Also unknown is the biological function or effects on the immune microenvironment of DCAF13. In this study, we parsed multiple public databases to explore the potential tumorigenic actions of DCAF13, including correlations with prognosis, microsatellite instability (MSI), tumor mutational burden (TMB), immune checkpoint genes, immune cell infiltration, and immunotherapy response in pan-cancer. Moreover, we validated DCAF13 expression in a tissue microarray by immunohistochemistry and investigate its effects in vitro and in vivo. The results showed that DCAF13 was upregulated in 17 cancer types and correlated with poor prognosis in many cancers. Also, the correlation between DCAF13 and TMB was found in 14 cancers as well as MSI in nine. The expression level of DCAF13 was found to be notably correlated with immune cell infiltration, showing a negative correlation with CD4 T cell infiltration and a positive correlation with neutrophil infiltration. The oncogene DCAF13 expression was shown to have a positive correlation with CD274 or ADORA2A and negative correlation with VSIR, TNFRSF4, or TNFRSF14 across large subsets of human cancers. Finally, we observed that DCAF13 was highly expressed in a tissue microarray of lung cancer. In immunocompromised mouse models, xenograft growth of human lung cancer cells was significantly inhibited by DCAF13 knockdown. Our results highlighted the value of DCAF13 as a promising independent predictor of poor prognosis through numerous biological processes. High DCAF13 expression often predicts suppressive immune microenvironment and immunotherapy resistance in a pan-cancer context.

Tumor-Infiltrating Immune Cell Landscapes in the Lymph Node Metastasis of Papillary Thyroid Cancer.

Regional lymph node metastasis (LNM) increases the risk of distant metastasis in papillary thyroid cancer (PTC) patients. However, it remains unclear how tumor cells in PTC patients with LNM evade immune system surveillance and proceed to colonize distant organs. Here, we comprehensively characterize the tumor-infiltrating immune cell landscape in PTC with LNM. LNM-related genes include multiple important soluble mediators such as CXCL6, IL37, MMP10, and COL11A1, along with genes involved in areas such as extracellular matrix organization and TLR regulation by endogenous ligands. In PTC without LNM, the tumor infiltration of activated dendritic cells and M0 macrophages showed increases from normal cells, but with yet greater increases and correspondingly worse prognosis in PTC with LNM. Conversely, the tumor infiltration of activated NK cells and eosinophils was decreased in PTC without LNM, as compared to normal cells, and yet further decreased in PTC with LNM, with such decreases associated with poor prognosis. We further demonstrate that mutations of driver genes in tumor cells influence the infiltration of surrounding immune cells in the tumor microenvironment (TME). Particularly, patients carrying TG mutations tend to show increased filtration of M2 macrophages and activated NK cells in the TME, whereas patients carrying HRAS mutations tend to show reduced filtration of M0 macrophages and show enhanced filtration of activated dendritic cells in the TME. These findings increase our understanding of the mechanisms of regional lymph node metastasis in PTC and its associated tumor microenvironment, potentially facilitating the development of personalized treatment regimens to combat immunotherapy failure.

Removal of a Foley catheter misplaced into the ureter by percutaneous puncture: a rare case report.

BACKGROUND: The incidence of aberrant catheterization into a ureter is extremely low, and there is a 20% chance that the balloon cannot be deflated. Regrettably, the mechanism underlying this complication remains unknown. There has been no reported case of a Foley catheter successfully removed from the ureter via percutaneous puncture. CASE PRESENTATION: A 86-year-old man complained of increasing abdominal pain after an 18F Foley catheter was inserted into his urethra. His attending physician attempted but failed to deflate the balloon. A bedside ultrasound and CT scan revealed that the catheter tip was in the right lower ureter. Several measures, including cutting the catheter and inserting a rigid guidewire, were then attempted but failed to deflate the balloon. Finally, the inflated balloon was punctured with a PTC needle under ultrasound-guidance, and the misplaced Foley catheter was removed. Two days after the pelvic drainage tube was removed, the patient was discharged. CONCLUSION: This is the first reported case of a Foley catheter being removed from the ureter via percutaneous puncture. The mechanism by which the balloon is unable to deflate may be related to the passive twist of the catheter. In such a case, an overall assessment of the patient's condition should be performed, and non-invasive to invasive interventions should be phased in.

Identification of Long Noncoding RNAs Associated With the Clinicopathological Features of Papillary Thyroid Carcinoma Complicated With Hashimoto's Thyroiditis.

Long noncoding RNAs (lncRNAs) play a significant role in cancer biology. This study aimed to determine the roles of lncRNAs in establishing the differences in clinical features between patients with papillary thyroid carcinoma (PTC) without Hashimoto's thyroiditis (HT) and patients with PTC and HT. In the present study, we detected the differentially expressed lncRNAs between tumor tissues of patients with PTC with or without HT through lncRNA microarrays. The data were verified and analyzed through qRT-PCR, cell viability, cell cycle and bioinformatics analyses. We found that 1031 lncRNAs and 1338 mRNAs were abnormally expressed in 5 tissue samples of PTC complicated with HT [PTC/HT (+)] compared with 5 samples of PTC without HT [PTC/HT (-)]. Gene Ontology and pathway analyses of the mRNAs suggested that several biological processes and pathways, particularly immune system processes, were induced in the PTC/HT (+) tissues. Twenty lncRNAs were verified in 31 PTC/HT (+) and 64 PTC/HT (-) specimens by qRT-PCR, and the results were consistent with the microarray data. Specifically, ENST00000452578, a downregulated lncRNA in PTC/HT(+), was negatively correlated with the tumor size. Cell viability assays revealed that ENST00000452578 could inhibit cell proliferation. Our results indicate that lncRNAs and mRNAs play an important role in establishing the different clinical characteristics between patients with PTC/HT(+) and patients with PTC/HT(-), and might provide new insights from the perspective of RNA for obtaining a further understanding of the clinical features related to PTC with HT.

Clearance of Chronic Actinic Dermatitis With Dupilumab Therapy in Chinese Patients: A Case Series.

Chronic actinic dermatitis (CAD) is a rare chronic immunological photo-dermatosis resulting in pruritic eczematous eruption on sun-exposed skin to ultraviolet (UV) light. The disease mechanism may include a delay-type hypersensitivity reaction to an endogenous photo-induced antigen, postulated to be UVR-altered DNA, but the exact pathophysiology is unknown. Minimum erythema dosing and patch testing are diagnostic tools of CAD. There are limited safe and effective treatment options for CAD. Herein, a case series of three patients with severe recalcitrant CAD is presented after being treated with dupilumab off-label. The patients in this study had persistent severe disease and taken the first-line management plan, which consists of topical calcineurin inhibitors (TCI), topical corticosteroids (TCS), and strict photoprotection. However, the above treatment options were not able to control the symptoms. The patients were treated with dupilumab 600 mg first dose, 300 mg biweekly subcutaneously (SC), and hydroxychloroquine. Dupilumab showed excellent clinical benefits, including safe and well-tolerated in chronic actinic dermatitis. Further studies are required to be carried out before being applied in clinical practice.

Risk factors of skip lateral cervical lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis.

OBJECTIVE: To analyze and explore the risk factors of skip lateral cervical lymph node metastasis (SLLNM) in papillary thyroid carcinoma (PTC). METHODS: PubMed, Web of Science, Embase, Cochrane, Wanfang, China National Knowledge Infrastructure, and China Science and Technology Journal databases, updated to April 4, 2021, were systematically searched for literature on the risk factors of SLLNM in PTC. The meta-analysis was completed using Stata 15.0 software after quality evaluation. The odds ratio (OR) and 95% confidence interval (CI) of each variable were calculated using fixed or random-effects models, and the publication bias was evaluated by the Egger's test. RESULTS: A total of 28 studies with 10,682 cases were included in our meta-analysis; 1592 (14.90%) cases were positive for SLLNM. The meta-analysis showed that female sex (OR = 1.16, 95% CI = 1.02-1.31, P = 0.021), age ≥45 (OR = 1.60, 95% CI = 1.19-2.15, P = 0.002), tumor diameter ≤10 mm (OR = 2.23, 95% CI = 1.62-3.06, P < 0.001), and upper location of tumor (OR = 3.60, 95% CI = 2.65-4.89, P < 0.001) were risk factors for SLLNM in PTC patients. Hashimoto's thyroiditis (OR = 1.02, 95% CI = 0.88-1.19, P = 0.777), multifocality (OR = 0.98, 95% CI = 0.75-1.28, P = 0.873), bilateral tumors (OR = 0.92, 95% CI = 0.70-1.19, P = 0.515), extrathyroidal extensions (OR = 1.07, 95% CI = 0.83-1.39, P = 0.598), and capsular invasion (OR = 0.93, 95% CI = 0.65-1.31, P = 0.660) were not closely related to SLLNM risk. CONCLUSION: This study confirmed significant associations between SLLNM and female sex, age ≥45, tumor diameter ≤10 mm, and upper location of the tumor.

A Novel Pyroptosis-Related Gene Signature for Prediction of Disease-Free Survival in Papillary Thyroid Carcinoma.

BACKGROUND: The incidence and recurrence rate of papillary thyroid carcinoma (PTC) are high. Thus, it is critical to accurately identify patients at high risk of recurrence. Pyroptosis is a type of programmed cell death closely related to the progression and prognosis of cancer. However, the role of pyroptosis in PTC remains unclear. METHODS: Transcriptome data for PTC patients were obtained from The Cancer Genome Atlas database. The expression level of pyroptosis-related genes (PRGs) in PTC and normal tissues was identified. Based on these differentially expressed genes, a risk score model of disease-free survival (DFS) was established using least absolute shrinkage and selection operator Cox regression. In-cluster and quantitative real-time PCR validations were carried out. A nomogram, in combination with clinical factors, was also established. In addition, its relationship with immune characteristics and tumor gene mutations is discussed. RESULTS: A risk score model with four PRGs, including CASP6, CASP9, IL-18, and NOD1, was established. The samples were divided into high- and low-risk clusters, according to the risk score, revealing significant differences in DFS between the two clusters. A nomogram was established combining age, lymph node metastasis and extrathyroidal extension. The area under the curve (AUC) of predicting one-, five-, and 10-year DFS in PTC patients was 0.745, 0.801, and 0.803, respectively. The low-risk cluster showed higher levels of immune infiltration and immune checkpoint gene expression, while the high-risk cluster demonstrated a higher tumor mutation burden. CONCLUSION: A predictive DFS model was established, based on PRGs, which may aid in identifying patients at high risk of recurrence. The present study helps to better understand the role of pyroptosis in the progression and prognosis of PTC.

The Prediction of Metastases of Lateral Cervical Lymph Node in Medullary Thyroid Carcinoma.

Purpose: Development and validation of a nomogram for the prediction of lateral lymph node metastasis (LLNM) in medullary thyroid carcinoma (MTC). Methods: We retrospectively reviewed the clinical features of patients with MTC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017 and in our Department of Surgical Oncology, Hangzhou First People's Hospital between 2009 and 2019. The log-rank test was used to compare the difference in the Kaplan-Meier (K-M) curves in recurrence and survival. The nomogram was developed to predict the risk of LLNM in MTC patients. The prediction efficiency of the predictive model was assessed by area under the curve (AUC) and concordance index (C-index) and calibration curves. Decision curve analysis (DCA) was performed to determine the clinic value of the predictive model. Result: A total of 714 patients in the SEER database and 35 patients in our department were enrolled in our study. Patients with LLNM had worse recurrence rate and cancer-specific survival (CSS) compared with patients without LLNM. Five clinical characteristics including sex, tumor size, multifocality, extrathyroidal extension, and distant metastasis were identified to be associated with LLNM in MTC patients, which were used to develop a nomogram. Our prediction model had satisfied discrimination with a C-index of 0.825, supported by both training set and internal testing set with a C-index of 0.825, and 0.816, respectively. DCA was further made to evaluate the clinical utility of this nomogram for predicting LLNM. Conclusions: Male sex, tumor size >38mm, multifocality, extrathyroidal extension, and distant metastasis in MTC patients were significant risk factors for predicting LLNM.

Extranodal Extension Is an Independent Prognostic Factor in Papillary Thyroid Cancer: A Propensity Score Matching Analysis.

Purpose: To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC). Methods: Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan-Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC. Results: Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS. Conclusions: Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.

A Novel Scoring System for Predicting the Metastases of Posterior Right Recurrent Laryngeal Nerve Lymph Node Involvement in Patients With Papillary Thyroid Carcinoma by Preoperative Ultrasound.

Objective: Our goal was to investigate the correlation between papillary thyroid carcinoma (PTC) characteristics on ultrasonography and metastases of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN). There is still no good method for clinicians to judge whether a patient needs LN-prRLN resection before surgery, and we also wanted to establish a new scoring system to determine whether patients with papillary thyroid carcinoma require LN-prRLN resection before surgery. Patients and Methods: There were 482 patients with right or bilateral PTC who underwent thyroid gland resection from December 2015 to December 2017 recruited as study subjects. The relationship between the PTC characteristics on ultrasonography and the metastases of LN-prRLN was analyzed by univariate and logistic regression analyses. Based on the risk factors identified in univariate and logistic regression analysis, a nomogram-based LN-prRLN prediction model was established. Result: LN-prRLN were removed from all patients, of which 79 had LN-prRLN metastasis, with a metastasis rate of 16.39%. Multivariate logistic regression analysis revealed that LN-prRLN metastasis was closely related to sex, age, blood supply, larger tumors (> 1 cm) and capsular invasion. A risk prediction model has been established and fully verified. The calibration curve used to evaluate the nomogram shows that the consistency index was 0.75 ± 0.065. Conclusion: Preoperative clinical data, such as sex, age, abundant blood supply, larger tumor (> 1 cm) and capsular invasion, are positively correlated with LN-prRLN metastasis. Our scoring system can help surgeons non-invasively determine which patients should undergo LN-prRLN resection before surgery. We recommend that LN-prRLN resection should be performed when the score is above 103.1.

Identification of novel biomarkers in Hunner's interstitial cystitis using the CIBERSORT, an algorithm based on machine learning.

BACKGROUND:  Hunner's interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC. METHODS: The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560. RESULTS: Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner's lesion and non-Hunner's lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen-antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560. CONCLUSION: This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.

Sirtuin 6 regulates the proliferation and survival of clear cell renal cell carcinoma cells via B-cell lymphoma 2.

Sirtuin 6 (SIRT6) is a member of the third family of longevity proteins (SIRTs) that is involved in the development of different types of cancer. However, the potential role of SIRT6 in clear cell renal cell carcinoma (ccRCC) and its molecular mechanism have not yet been fully elucidated. Therefore, the present study aimed to investigate the association between SIRT6 and ccRCC, and to further examine the underlying mechanism of its effect on ccRCC proliferation, using bioinformatics analysis, and in vitro and in vivo experiments. The results of the present study demonstrated that SIRT6 was upregulated in ccRCC tissues. In addition, bioinformatics analysis revealed that high SIRT6 expression was closely associated with poor prognosis of patients with ccRCC. In vitro experiments demonstrated that silencing SIRT6 expression in ccRCC-derived 769-P and 786-O cells significantly inhibited their proliferation, migration and invasion. Consistent with these results, in vivo assays demonstrated that SIRT6 knockdown markedly attenuated tumor growth arising from 769-P cells. Furthermore, depletion of SIRT6 enhanced the sensitivity of ccRCC cells to cisplatin. Notably, silencing SIRT6 expression decreased B-cell lymphoma 2 (Bcl-2) expression and increased Bax expression, respectively. Taken together, these results suggest that SIRT6 acts as a proto-oncogene in ccRCC through the augmentation of the Bcl-2-dependent pro-survival pathway, and may be used as a therapeutic target for patients with ccRCC.

The Anatomical and Clinical Significance of the Superior Laryngeal Nerve.

OBJECTIVE: This study summarizes the anatomical features of the superior laryngeal nerve in Chinese to enable the rapid location of the superior laryngeal nerve during an operation. STUDY DESIGN: Retrospective analysis of anatomical data. SETTING: Hangzhou First People's Hospital Affiliated to Nanjing Medical University. METHODS: A total of 71 embalmed human cadavers (132 heminecks) were examined over 3 months. The length and diameter of the internal and external branches of the superior laryngeal nerve and their relationships with different landmarks were recorded. RESULTS: The total length of the internal branch of the superior laryngeal nerve was 23.4 ± 6.9 mm. The length of the external branch of the superior laryngeal nerve was 47.7 ± 11.0 mm. Considering the midpoint of the lower edge of the thyroid cartilage as the starting point and using that edge as a horizontal line, when the entry point is above that line, the external branch of the superior laryngeal nerve can be found within 41.1 mm and at an angle of 57.2°. When the entry point is below the lower edge of the thyroid cartilage, the external branch of the superior laryngeal nerve can be found within 34.0 mm and at an angle of 36.5°. CONCLUSION: The superior laryngeal nerve in Chinese people has distinct anatomical characteristics. This article provides a new method of quickly locating the external branch of the superior laryngeal nerve during the operation, which can reduce the probability of damaging the external branch of the superior laryngeal nerve.

Risk factors for lateral cervical lymph node metastasis in medullary thyroid carcinoma.

: To investigate risk factors of lateral cervical lymph node metastasis (LLNM) in patients with medullary thyroid carcinoma (MTC). : Published studies regarding clinicopathological factors of LLNM in MTC were searched in PubMed, Web of Science, Embase, Cochrane library, Wanfang date and CNKI. Statistical analysis was performed using Stata 14.0 software. The mean and standard deviation from the sample size, range, median, and interquartile range was estimated. Odds ratio () or standard mean difference () with 95% confidence interval () of related factors were analyzed by fixed/random-effects models. Egger's test and Begg's test were applied to assess the publication bias of the literature. This study was registered with PROSPERO (CRD42021254955). : Fifteen studies involving 1424 patients were included in the analysis, among whom 543 cases had LLNM (38.13%). Meta-analysis revealed that an increased risk of LLNM was associated with male gender (1.64, 95%: 1.29-2.09, 4.06, 0.01), tumor diameter≥1cm (5.09, 95%: 2.43-10.67, 4.31, 0.01), multifocality (2.55, 95%: 1.79-3.61, 5.22, 0.01), capsule invasion (7.80, 95%: 4.84-12.55, 8.46, 0.01), extracapsular extension (9.46, : 5.66-15.81, 8.58, 0.01), cervical central lymph node metastasis (23.58, : 9.44-58.87, 6.77, 0.01), elevated preoperative calcitonin (1.17,95%: 0.67-1.67, 4.56, 0.01), spiculated margin on ultrasonography (4.32, 95%: 2.43-7.68, 4.99, 0.01), irregular shape on ultrasonography (6.81, : 3.64-12.73, 6.01, 0.01); while age ≥ 45 years (=1.22, 95%: 0.65-2.29, 0.62, >0.05), elevated preoperative carcinoembryonic antigen (0.95, : -0.48-2.38, 1.30, >0.05) and calcification on ultrasonography (1.28, 95%: 0.75-2.18, 0.92, >0.05) were not associated with LLNM. : Male gender, tumor diameter≥multifocality, capsule invasion, extracapsular extension, central lymph node metastasis, elevated preoperative calcitonin, spiculated margin and irregular shape on ultrasonography are risk factors for LLNM in MTC, when these clinical and ultrasonic features are present, lateral neck lymph node dissection is recommended.

Off-clamp Retroperitoneoscopic Tumour Evacuation for Sporadic Renal Angiomyolipomas with High RENAL Nephrometry Scores: A Novel Surgical Technique and Its Outcomes.

BACKGROUND: Partial nephrectomy or angioembolisation is commonly used for sporadic renal angiomyolipomas (RAMLs) with high RENAL scores, but there is a risk of reduced renal function, postoperative complications, and recurrence. OBJECTIVE: To describe a new technique for off-clamp laparoscopic evacuation of sporadic RAMLs with high RENAL scores that promotes maximal renal function maintenance and low postoperative complication and lesion recurrence rates. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort of patients undergoing off-clamp laparoscopic evacuation for sporadic RAMLs with RENAL scores ≥9 from January 2013 to June 2018 was included. SURGICAL PROCEDURE: We highlighted the curettage, suction, packing, and binding (CSPB) technique, a new off-clamp retroperitoneoscopic evacuation technique for sporadic RAMLs. MEASUREMENTS: Demographics, preoperative, intraoperative, and postoperative outcomes were assessed. RESULTS AND LIMITATIONS: A total of 141 cases were included. The median (interquartile range [IQR]) tumour size was 7 (6.2-8.2)cm. The median (IQR) RENAL score was 10 (9-11). The median (IQR) operative time was 80 (65-125) min, with a median (IQR) estimated blood loss of 130 (90-362.5)ml. Conversion to neither open surgery nor standard laparoscopy occurred. The warm ischaemia time was zero for all cases. Postoperatively, 13 minor complications (Clavien grade 1) were recorded. No blood transfusions were reported. The glomerular filtration rate did not change significantly from preoperative period to 12-mo follow-up. Recurrence did not occur at the median follow-up period of 48 (36-60) mo. The retrospective design and lack of a control group are limitations of this study. CONCLUSIONS: Off-clamp retroperitoneoscopic tumour evacuation using the CSPB technique is feasible, safe, and effective for treating complex sporadic RAMLs. PATIENT SUMMARY: We report a curettage, suction, packing, and binding technique for off-clamp retroperitoneoscopic evacuation of sporadic renal angiomyolipomas that leads to complete lesion clearance, excellent renal function preservation, and minimal perioperative complications.

Histone deacetylase 2 is involved in DNA damage-mediated cell death of human osteosarcoma cells through stimulation of the ATM/p53 pathway.

Tumor suppressor p53 is a short-lived nuclear transcription factor, which becomes stabilized and activated in response to a wide variety of cellular stresses. Around 50% of human cancer tissues carry p53 mutations, and certain p53 mutations contribute to chemoresistance. In the present study, we found that histone deacetylase 2 (HDAC2) acts as a co-activator of tumor suppressor p53 and participates in the early molecular events following DNA damage. Anti-cancer drug adriamycin (ADR) treatment induced cell death in p53-wild-type human osteosarcoma U2OS cells, and this was accompanied by a remarkable accumulation of p53 and γH2AX. HDAC2 gene silencing significantly decreased the sensitivity of U2OS cells to ADR and attenuated p53-dependent DNA damage responses, such as ADR-mediated phosphorylation of ataxia telangiectasia mutated (ATM) and p53, as well as accumulation of γH2AX and cleaved poly (ADP-ribose) polymerase. However, HDAC2 knockdown had a marginal effect on p53-null human lung cancer H1299 cells following ADR exposure. In contrast, forced expression of HA-HDAC2 promoted cell death and stimulated the transcriptional activity of p53. Moreover, p53 and HDAC2 were found to co-precipitate with ATM. Together, our present results strongly suggest that the p53-HDAC2 axis plays a vital role in the regulation of the DNA damage response and also contributes to chemosensitivity of cancer cells.

Scientometric Analysis of SIRT6 Studies.

BACKGROUND SIRT6 is a molecule of significant interest in the field of epigenetics. This review of the literature aimed to explore research hotspots and other bibliometric features of SIRT6 by applying several bibliometric analysis tools and by establishing a comprehensive scientometric analysis model of SIRT6. MATERIAL AND METHODS The research sample included 441 articles related to SIRT6 obtained from the Web of Science core collection. Bicomb software was used to extract high frequency keywords, and then a binary matrix and a co-word matrix were constructed. We used Gcluto for double clustering, EXCEL for strategic coordinate building, Citespace software for co-citation analysis, CitNetExplorer for citation analysis, and Vosviewer for journal and term analysis. RESULTS Research hotspots and the base knowledge of SIRT6 were determined by co-word and co-citation network analysis. The strategic coordinates approach was used to assess the research prospects of each hotspot and the connections between these hotspots. The distribution of disciplines and journals was determined and both a term density map and a dual-map were constructed by application of different tools. CONCLUSIONS SIRT6's regulation of chromatin, lifespan, DNA damage, and metabolism make up the most important SIRT6 intellectual basis from the past 10 years. SIRT6 study has concentrated on the effects of this molecule on tumors and shown promising trends in understanding neural diseases. However, there has been little analysis of how SIRT6 effects are part of more complex systems. Work by Motoslavsky (2006) represents a milestone in SIRT6 research, and the studies by Kawahara 2009 and Kim 2010 are key in the knowledge transmission of SIRT6 research.