Recurrent laryngeal never monitoring versus non-monitoring in parathyroid surgery.

Background: Although intraoperative neural monitoring (IONM) is well established in thyroid surgery, it is less commonly analyzed in parathyroid operations. This study presents the results of IONM for primary and secondary hyperparathyroidism surgery. Methods: We retrospectively assessed 270 patients with primary hyperparathyroidism (PHPT), 53 patients with secondary hyperparathyroidism (SHPT), and 300 patients with thyroid cancer from June 2010 to June 2022 in one hospital in China. The follow-up was 12 months. Demographic, electromyography data from IONM, laboratory, and clinical information were collected. Laryngoscopy was collected from 109 patients with PHPT in whom IONM was not used. All groups were assessed by Pearson's chi-square test and Fisher's exact probability method to verify the relationship between parathyroid size and location, duration of surgery, preoperative concordant localization, laryngeal pain, IONM outcomes, cure rate, and RLN injury. Visual analog scale (VAS) assessed laryngeal pain. RLN outcomes were measured according to nerves at risk (NAR). Results: The study comprehended 918 NAR, that is 272, 105, 109, and 432 NAR for PHPT, SHPT with IONM, PHPT without IONM, and thyroid surgery control group, respectively. IONM successfully prevented RLN injury (P<0.001, P=0.012): Fifteen (5.51%) RLNs experienced altered nerve EMG profiles during surgery, and five (1.84%) experienced transient RLN injury in PHPT patients. Five (4.76%) RLNs were found to have altered EMG profiles during surgery, and one (0.95%) RLN had a transient RLN injury in SHPT patients. There was no permanent nerve injury (0.00%) in this series. There was no association between location, gland size, preoperative concordant localization, cure rate, duration of surgery, and IONM (P >0.05). Duration of surgery was associated with postoperative pharyngeal discomfort (P=0.026, P=0.024). Transient RLN injury was significantly lower in patients with PHPT who underwent IONM than in those who did not. Intraoperative neuromonitoring played an effective role in protecting the recurrent laryngeal nerve (P=0.035). Compared with parathyroidectomy, thyroidectomy had a higher rate of RLN injury (5.32%, P<0.001). Conclusion: IONM for SHPT and PHPT offers rapid anatomical gland identification and RLN functional results for effective RLN protection and reduced RLN damage rates.

Factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients.

Background: Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients. Methods: The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses. Results: First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels. Conclusion: Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis.

Two cases of concurrent carcinoma showing thymus-like differentiation (CASTLE) coexisting with papillary thyroid carcinoma.

Carcinoma showing thymus-like differentiation (CASTLE), which emerges within the thyroid gland or the adjacent soft tissues of the neck, is a rare malignant neoplasm found globally. The occurrence of CASTLE in conjunction with papillary thyroid carcinoma is an even more infrequent phenomenon. The ensuing sections elaborate upon the clinical attributes characteristic of CASTLE.

LINC00365 functions as a tumor suppressor by inhibiting HIF-1α-mediated glucose metabolism reprogramming in breast cancer.

Long non-coding RNAs (lncRNAs) play an important role in regulating several physiological processes and have been implicated in several pathologies including cancer. LncRNAs have been found to regulate key cellular pathways involved in cancer development, and their aberrant expression plays critical roles in the onset or progression of disease. The role of lncRNAs in breast cancer (BC) has become a hot topic of research in recent years. We previously showed that LINC00365 inhibits BC survival. In the current study, based on the important role of energy metabolism and HIF-1α for tumor cell proliferation, we investigated the role and mechanism of the LINC00365/HIF-1α axis in affecting tumor growth through glycolysis using the breast cancer cell lines MCF-7 and HCC-1937. We found that LINC00365 inhibited BC cell proliferation. Furthermore, LINC00365 overexpression suppressed aerobic glycolysis in BC cells. RNA-sequencing identified hypoxia-inducible factor-1α (HIF-1α), which has been linked with glycolysis and upregulates glycolysis-related genes, as a potential target gene of LINC00365. Accordingly, we found that LINC00365 overexpression resulted in decreased expression of key glycolytic enzymes such as downstream hexokinase 2 (HK2), recombinant pyruvate kinase isozymes M2 (PKM2) and lactate dehydrogenase A (LDHA). Our results suggest that targeting LINC00365 may reverse the glucose metabolism pattern of BC and effectively inhibit BC survival both in vitro and in vivo.

Origin verification of French red wines using isotope and elemental analyses coupled with chemometrics.

Origin verification of 240 French wines from four regions of France was undertaken using isotope and elemental analyses. Our aim was to identify and differentiate the geographical origin of these red wines, and more importantly, to build a classification tool that can be used to verify geographic origin of French red wines using machine learning models. Multivariate analyses of the isotopic and elemental data revealed that it is possible to determine the geographical origin of French wines with a high level of confidence for most regions analyzed in this study. The wine verification accuracy of four French wine producing regions of Bordeaux, Burgundy, Languedoc-Roussillon and Rhone using an Artificial Neural Network (ANN) method was 98.2%. The results also show that ANN is more suitable than Discriminant Analysis for this verification purpose. The most important variables for French wine regional traceability were Mg, Mn, Na, Sr, Ti and Rb.

Comparison of iPTH and calcium levels between total thyroidectomy and lobectomy: a prospective study of 840 thyroid cancers with three years of follow-up.

BACKGROUND: Hypocalcemia is the most frequent complication after thyroidectomy and central neck dissection (CND). Early intact parathyroid hormone (iPTH) determination has been proposed as an early predictor parathyroid gland state. We aim to describe iPTH kinetics after central compartment lymph node dissection (CLND). METHODS: A large prospective observational study was conducted among 840 patients who underwent thyroid cancer surgery between July and December 2016 in China-Japan Union Hospital of Jilin University. Data were obtained from the patient's iPTH evaluation 15 min after CND and serum calcium records during three years of post-operative follow-up. Age, sex, BMI, preoperative PTH, operative and pathologic details were analyzed. Backward stepwise logistic regression analyses were performed to find potential risk factors for predicting iPTH <15 pg/mL. The odds ratio and 95% confidence interval are estimated using the logistic regression coefficients. The prediction model was assessed using the receiver operating characteristic curve. RESULTS: The incidence of permanent hypocalcemia was 0.12%, while, 44.52% of patients were central lymph node metastasis. Multivariate analyses found associations among iPTH <15 pg/mL and several risk factors, especially preop PTH and type of surgery. The risk of iPTH <15 pg/mL, after total thyroidectomy plus CND, is almost 17 times that of lobectomy plus CND (OR =17.648, 95% confidence interval: 10.011-31.110). A model was created using multivariate analysis, which involved surgical procedure, and preop PTH could separate thyroid operation with iPTH <15 pg/mL. The biological index showed an area under the ROC curve of 0.697 and 0.613 separately. Using values below the lowest or above the highest cut-off point, the presence or absence of iPTH <15 pg/mL could possibly be predicted before thyroidectomy and CND. CONCLUSIONS: A lobectomy procedure for papillary thyroid carcinoma patients with clinically uninvolved neck lymph nodes (cN0) who have primary tumors (T1 or T2) could accompany prophylactic CND (ipsilateral or bilateral) to provide clearance of disease compared to total thyroidectomy.

LINC00365-SCGB2A1 axis inhibits the viability of breast cancer through targeting NF-κB signaling.

Breast cancer is the most common high-grade malignancy in women. The lack of therapeutic targets has limited the treatment of breast cancer. Recently, long noncoding RNAs (lncRNAs) have been demonstrated to be dysregulated in various types of cancer. However, the specific mechanisms by which lncRNAs influence breast cancer have remained largely unclear. To bridge this research gap, the present study focused on the lncRNA LINC00365, which is expressed at a low level in breast cancer. Secretoglobin family 2A member 1 (SCGB2A1) was identified as a potential target protein regulated by LINC00365. The results of the present study demonstrated that the overexpression of LINC00365 and SCGB2A1 inhibited cell viability and induced cell apoptosis through the inhibition of the NF-κB signaling pathway in breast cancer cells. These findings indicated that LINC00365 may serve a crucial role in breast cancer and may be considered as a novel target for the clinical treatment of breast cancer.

[Rapid screening and determination of fentanyl and its analogues in drugs by liquid chromatography- quadrupole time-of-flight mass spectrometry].

A method based on liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was developed for the simultaneous screening and determination of fentanyl and its 26 analogs in liquid and solid powder drugs. The established method involves successive extraction by 5 mL 75% (v/v) acetonitrile aqueous solution and 5 mL acetonitrile, followed by clean-up using the hydrophilic lipophilic balance (HLB) solid-phase extraction method. Detection was achieved by electrospray ionization (ESI) in the positive mode, TOF-MS, and information-dependent acquisition (IDA)-MS/MS acquisition; the external standard method was adopted for quantification. Two databases of accurate mass and fragment ions were created. The standard matrix-matched calibration curves of the 27 target compounds were linear in the range of 5.00-100 µg/L, with the correlation coefficients (r2)>0. 99. The limits of quantification for the 27 target compounds were 10.0 µg/kg. The recoveries for all the target compounds in vitamin C tablet, headache powder, cough syrup, and transdermal patch samples were in the ranges of 82.9%-106%, 84.8%-106%, 86.9%-109%, and 83.1%-106%, respectively, with relative standard deviations ranging from 0.38% to 8.71% (n=6). The results demonstrated that the developed method is rapid and sensitive for the simultaneous monitoring and determination of fentanyl and 26 its analogs in liquid and solid powder drugs.

Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p.

The principal issue derived from thyroid cancer is its high propensity to metastasize to the lymph node. Aberrant exprssion of long non-coding RNAs have been extensively reported to be significantly correlated with lymphatic metastasis of thyroid cancer. However, the clinical significance and functional role of lncRNA-MAPK8IP1P2 in lymphatic metastasis of thyroid cancer remain unclear. Here, we reported that MAPK8IP1P2 was downregulated in thyroid cancer tissues with lymphatic metastasis. Upregulating MAPK8IP1P2 inhibited, while silencing MAPK8IP1P2 enhanced anoikis resistance in vitro and lymphatic metastasis of thyroid cancer cells in vivo. Mechanistically, MAPK8IP1P2 activated Hippo signaling by sponging miR-146b-3p to disrupt the inhibitory effect of miR-146b-3p on NF2, RASSF1, and RASSF5 expression, which further inhibited anoikis resistance and lymphatic metastasis in thyroid cancer. Importantly, miR-146b-3p mimics reversed the inhibitory effect of MAPK8IP1P2 overexpression on anoikis resistance of thyroid cancer cells. In conclusion, our findings suggest that MAPK8IP1P2 may serve as a potential biomarker to predict lymphatic metastasis in thyroid cancer, or a potential therapeutic target in lymphatic metastatic thyroid cancer.

Diagnosis, anatomy, and electromyography profiles of 73 nonrecurrent laryngeal nerves.

BACKGROUND: The purpose of this work was to compare methods of detecting nonrecurrent laryngeal nerves (NRLNs). METHODS: Specificity and sensitivity were compared in three NRLN detection methods: CT, electromyography (EMG), and A-B point comparison. RESULTS: A total of 73 intraoperative pictures and 36 CT details of NRLNs are presented. Incidence of NRLN was 0.39%. Type I NRLN accounted for 50.7%, type IIA 45.2%, type IIB 4.1%. The NRLN median latency was 2.13 ms vs 3.00 ms median in an RLN control group (P < .001). When the threshold was set to 2.5 ms, EMG latency detection had 96.7% sensitivity and 91.6% specificity for detecting NRLN, and the A-B point comparison algrithm had 97.3% sensitivity and 92.5% specificity. Combining EMG latency detection with A-B point comparison achieved 100% sensitivity and specificity for detecting NRLN. CONCLUSION: This is the largest series of NRLN presented in the literature. Latency shorter than 2.50 ms combined with the A-B point comparison method is the ideal algorithm procedure for early NRLN identification.

HDAC9 overexpression confers invasive and angiogenic potential to triple negative breast cancer cells via modulating microRNA-206.

Triple negative breast cancer (TNBC) is among the most aggressive breast cancer subtypes with poor prognosis. The purpose of this study is to better understand the molecular basis of TNBC as well as develop new therapeutic strategies. Our results demonstrate that HDAC9 is overexpressed in TNBC compared to non-TNBC cell lines and tissues and is inversely proportional with miR-206 expression levels. We show that HDAC9 selective inhibition blocked the invasion of TNBC cells in vitro and repressed the angiogenesis shown via in vivo Matrigel plug assays. Subsequent HDAC9 siRNA knockdown was then shown to restore miR-206 while also decreasing VEGF and MAPK3 levels. Furthermore, the inhibition of miR-206 neutralized the action of HDAC9 siRNA on decreasing VEGF and MAPK3 levels. This study highlights HDAC9 as a mediator of cell invasion and angiogenesis in TNBC cells through VEGF and MAPK3 by modulating miR-206 expression and suggests that selective inhibition of HDAC9 may be an efficient route for TNBC therapy.

HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL.

Although histone deacetylase (HDAC) inhibitors have been shown to effectively induce the inhibition of proliferation and migration in breast cancer, the anticancer mechanism remains poorly understood. Our studies show that miR-200c was significantly downregulated in breast cancer cell lines compared to normal cell lines and inversely correlated with the levels of class IIa HDACs and CRKL. HDAC inhibitors and the ectopic expression of miR-200c as tumor suppressors inhibited the proliferation, invasion, and migration of breast cancer cells by downregulating CRKL. These results indicate that the anticancer mechanism of HDAC inhibitor was realized partially by regulating miR-200c via CRKL targeting. Our findings suggest that the HDAC-miR200c-CRKL signaling axis could be a novel diagnostic marker and potential therapeutic target in breast cancer.

Downregulation of microRNA-206 promotes invasion and angiogenesis of triple negative breast cancer.

Triple negative breast tumors don't respond to Tamoxifen and Herceptin, two of the most effective medications for treating breast cancer. Additionally, triple negative breast cancer (TNBC) intrinsically resists or will eventually acquire resistance to chemotherapy. The purpose of this study is to understand better the molecular basis of TNBC as well as develop new therapeutic strategies against it. Here, we analyzed miRNA-206 expression levels in breast cancer cell lines and tissues. In addition, we investigated whether miR-206 mimics inhibited TNBC tumor invasion and angiogenesis. The results showed that miR-206 was downregulated in TNBC compared to non-TNBC cell lines and tissues. Additionally, the decreased levels of miR-206 were inversely consistent with expression levels of VEGF. Furthermore, the forced expression of miR-206 in the mimic-transfected TNBC cells downregulated VEGF, MAPK3, and SOX9 expression levels. The miR-206 mimics inhibited TNBC breast cell invasion and angiogenesis. These findings demonstrate for the first time the involvement of miRNA-206 in TNBC invasion and angiogenesis and suggest that miR-206 may be an efficient agent for therapy of TNBC.

Applicability of rapid intraoperative parathyroid hormone assay through fine needle aspiration to identify parathyroid tissue in thyroid surgery.

Hypoparathyroidism is a frequent and serious complication of thyroid surgery. Identification and preservation of the parathyroid glands are key factors in managing hypoparathyroidism. The aim of the present study was to investigate the efficacy of rapid intraoperative parathyroid hormone (rIO-PTH) assay levels through fine needle aspiration (FNA) in identifying parathyroids as a parameter in thyroid surgery. rIO-PTH assay through FNA and frozen section examination were performed on 194 suspected parathyroids anatomical structures from 50 consecutive patients undergoing thyroidectomy (rIO-PTH group). The association between the rIO-PTH values and histological results were analyzed. Clinical effects were compared between the rIO-PTH and control groups from 50 patients undergoing a similar standard surgery. rIO-PTH levels from 93/194 aspirated anatomical structures certified as parathyroid tissues by histological analysis were demonstrated to have a mean of 3,369 pg/ml (range, 145.2-5,000 pg/ml). These values were significantly increased compared with the mean value of 25.7 pg/ml from non-parathyroids tissues significantly (P<0.001). The mean number of 3.76 on the recognized parathyroids was obtained by naked eye measurements combined with rIO-PTH assay through FNA, was significantly higher than compared with only naked eye measurements (P<0.05). Postoperative permanent or transient hypoparathyroidism was not detected in the rIO-PTH groups. The difference between the postoperative serum calcium level and blood PTH values of rIO-PTH and control groups was not statistically significant (P>0.05). The value of rIO-PTH assay through FNA demonstrated that it is a good parameter for differentiating parathyroids and non-parathyroids tissues. The technique is a highly reliable, quick, simple and non-invasive method with a short learning curve in thyroid surgery, which is particularly valuable for inexperienced surgeons. This method may replace frozen section examination, which relies on a surgeon's personal experience on the basis of topographic or morphologic criteria for recognizing parathyroids.

Expression and clinical significance of Shh/Gli-1 in papillary thyroid carcinoma.

The Sonic Hedgehog (Shh) pathway affects cancer initiation, progression, and metastasis, but its role in papillary thyroid carcinoma (PTC) remains elusive. To characterize expression and clinical significance of Shh and the transcription factor Gli-1-the key elements of the Shh pathway in PTC tissues-we immunohistochemically examined Shh/Gli-1 expression in PTC tissues from 142 patients, along with adjacent non-cancerous tissues as controls. We reviewed 142 patients' clinical characteristics and analyzed their relationship with expression of Shh/Gli-1. Shh and Gli-1 were expressed in 64.1 % (91/142) and 47.9 % (68/142) in PTC tissues, respectively, compared with 16.9 % (24/142) and 9.2 % (13/142) of adjacent non-cancerous tissues. Gli-1 expression was significantly associated with patients' ages (P < 0.05) and lymph node metastasis (P < 0.01). Increased Shh and Gli-1 expression was significantly associated with tumor-node-metastasis (TNM) stage (P < 0.01). Shh and Gli-1 were expressed in 79.2 and 60.4 %, respectively, of PTC tumors larger than 10 mm. Shh was significantly associated with tumor size (P < 0.01). Shh and Gli-1 were expressed in 72.5 and 65.2 %, respectively, of patients with lymph node metastasis. Overall, we found increased expression of the main initiator Shh and transcription factor Gli-1 in Shh pathway in PTC tissues. The expression of Shh/Gli-1 was significantly associated with tumor size, clinical staging, and lymph node metastasis, indicating that aberrant activation of the Shh pathway is important to PTC occurrence and progression. Potentially, Shh/Gli-1 could be a diagnostic indicator and a marker of therapeutic response.

Inhibition of breast cancer metastasis with microRNA-302a by downregulation of CXCR4 expression.

Metastasis remains a main cause of mortality from breast cancer and an unresolved issue. The purpose of this study is to investigate the role of miR-302a in the development of breast cancer metastasis mediated by CXCR4, a critical regulator of metastasis, and to identify miR-302a as an effective therapeutic agent for therapy and prevention of breast cancer metastasis. Our studies show that miR-302a expression levels were downregulated in metastatic breast cancer cells and tumor tissues. Additionally, the expression levels of miR-302a were inversely correlated with CXCR4 levels. More promisingly, miR-302a inhibited the invasion and metastasis of breast cancer cells in vitro and in vivo and reduced the expression of CXCR4. Our findings demonstrated that the repression of miR-302a levels contributes to breast cancer metastasis and restoration of miR-302a baseline expression inhibits the invasion and metastasis of breast cancer cells. These data suggest that miR-302a mimics are potential therapeutic agents for breast cancer metastasis.