Effects of astragaloside IV on glucocorticoid-induced avascular necrosis of the femoral head via regulating Akt-related pathways.

We investigated the role of astragaloside IV (AS-IV) in preventing glucocorticoid-induced avascular necrosis of the femoral head (ANFH) and the underlying molecular mechanisms. Network pharmacology was used to predict the molecular targets of AS-IV. Molecular dynamic simulations were performed to explore the binding mechanism and interaction mode between AS-IV and Akt. Rat models of glucocorticoid-induced ANFH with AS-IV intervention were established, and osteogenesis, angiogenesis, apoptosis and oxidative stress were evaluated before and after blocking the PI3K/Akt pathway with LY294002. The effects of glucocorticoid and AS-IV on bone marrow mesenchymal stem cells and human umbilical vein endothelial cells incubated with and without LY294002 were determined. Downregulated p-Akt expression could be detected in the femoral heads of glucocorticoid-induced ANFH patients and rats. AS-IV increased trabecular bone integrity and vessel density of the femoral head in the model rats. AS-IV increased Akt phosphorylation and upregulated osteogenesis-, angiogenesis-, apoptosis- and oxidative stress-related proteins and mRNA and downregulated Bax, cleaved caspase-3 and cytochrome c levels. AS-IV promoted human umbilical vein endothelial cell migration, proliferation and tube formation ability; bone marrow mesenchymal stem cell proliferation; and osteogenic differentiation under glucocorticoid influence. AS-IV inhibited apoptosis. LY294002 inhibited these effects. AS-IV prevented glucocorticoid-induced ANFH by promoting osteogenesis and angiogenesis via the Akt/Runx2 and Akt/HIF-1α/VEGF pathways, respectively, and suppressing apoptosis and oxidative stress via the Akt/Bad/Bcl-2 and Akt/Nrf2/HO-1 pathways, respectively.

Diagnostic Performance of Atherosclerotic Carotid Plaque Neovascularization with Contrast-Enhanced Ultrasound: A Meta-Analysis.

Objectives: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for atherosclerotic carotid plaque neovascularization. Methods: The electronic databases like PubMed, Embase, OVID, and Web of Science were used to search for the relevant studies, which are involved in the evaluation of the diagnostic parameters of QUS for atherosclerotic carotid plaque neovascularization. Review Manager 5.4 and Stata 14.0 were used to estimate the pooled diagnostic value of CEUS. Forest plots, sensitivity analysis, and Deeks' funnel plots were performed on the included studies. Results: Ten studies eventually met the final inclusion criteria. For diagnostic performance, CUES showed that the pooled values of sensitivity, specificity, positive likelihood odds ratios, negative likelihood odds ratios, and diagnostic odds ratios were 0.83 (95% CI 0.78-0.86), 0.77 (95% CI 0.68-0.84), 3.61 (95% CI 2.59-5.03), 0.23 (95% CI 0.18-0.28), and 16.02 (95% CI 10.02-25.60), respectively. The estimate of the area under curve (AUC) was 0.85 (95% CI 0.82-0.88). Conclusion: Our research supported that CEUS had high sensitivity and specificity in the diagnosis of atherosclerotic carotid plaque neovascularization. More high-quality prospective multicenter studies focusing on the accuracy of CEUS for carotid atherosclerotic plaque should be performed to verify our conclusions.

Risk factors of skip lateral lymph node metastasis in papillary thyroid carcinoma.

PURPOSE: Cervical lymph node metastasis is a prognostic factor of papillary thyroid carcinoma (PTC). This study aimed to investigate clinicopathological features and risk factors of skip lateral lymph node metastasis in PTC patients. METHODS: We retrospectively reviewed medical records of patients who underwent simultaneous total thyroidectomy with therapeutic central compartment lymph node dissection (LND) and lateral LND for primary PTC from 2014 to 2019. Univariate and multivariate logistic regression analyses were performed to identify clinicopathologic risk factors for skip metastasis. Receiver-operating characteristic (ROC) curves were constructed using the results of the multiple logistic regression analysis to identify data points with the highest sensitivity and lowest false-negative rate. RESULTS: The frequency of skip metastasis was approximately 12.8% (50/390). Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.008-1.059; P = 0.010), tumor size (OR 0.251; 95% CI 0.129-0.490; P < 0.001) and tumor located in the upper portion (OR 0.378; 95% CI 0.200-0.715; P = 0.003) were independent risk factors of skip metastasis (all P < 0.05). The ROC curves showed that the cut-off value of age for predicting skip metastasis was 44.5 years old (sensitivity = 0.620, specificity = 0.618, area under the curve [AUC] = 0.627, P = 0.004); the cut-off value of the tumor diameter for predicting skip metastasis was 1.05 cm (sensitivity = 0.503, specificity = 0.760, AUC = 0.682, P < 0.001). CONCLUSIONS: Skip metastasis was common in PTC. The PTC patients with age > 44.5 years, tumor diameter < 1.05 cm and tumor located in the upper portion should be carefully evaluated for skip metastasis.

m6A RNA methylation regulators have prognostic value in papillary thyroid carcinoma.

BACKGROUND: N6-Methyladenosine (m6A) is a ubiquitous RNA modification with vital roles in various cancers, but little is known about its role in papillary thyroid carcinoma (PTC), a common endocrine malignancy. METHODS: In this study, an m6A RNA methylation regulator-based biomarker signature was developed for the effective prediction of prognosis in patients with PTC. The gene expression profiles of m6A RNA methylation regulators and the corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed m6A RNA methylation regulators between tumor and normal control samples, and correlation expression levels, clinical parameters, and outcomes were evaluated. And a prognostic signature was built using a PTC cohort from TCGA. RESULTS: The expression level of HNRNPC was remarkably upregulated in tumor samples, while WTAP, RBM15, YTHDC2, YTHDC1, FTO, METTL14, METTL3, ALKBH5, KIAA1429, YTHDF1, and ZC3H13 were significantly downregulated in the cancer specimens compared with those in control samples. A three-gene prognostic signature comprising RBM15, KIAA1429, and FTO could predict overall survival in patients with PTC. In addition, the prognostic signature-based risk score was identified as an independent prognostic indicator for PTC. CONCLUSIONS: We established a robust m6A RNA methylation regulator-based molecular signature for predicting prognosis in patients with PTC with high accuracy; this signature might provide important guidance for therapeutic strategies.

Network meta-analysis of surgical treatment for secondary hyperparathyroidism.

BACKGROUND: Main surgical treatments for secondary hyperparathyroidism (SHPT) include subtotal parathyroidectomy (sPTX), total parathyroidectomy with autotransplantation (tPTX+AT), and total parathyroidectomy (tPTX); however, determining the best treatment is debatable. We conducted a network meta-analysis (NMA) comparing three treatments in terms of postoperative hypocalcemia (or hypoparathyroidism), postoperative recurrence, and reoperation. METHODS: We searched PubMed, Medline, the Cochrane Library, and Embase for relevant research from inception to July 30, 2019. We performed our Bayesian NMA using R 3.51 software to assess odds ratios (OR) and 95% confidence intervals (CI). Network and forest plots displayed study outputs. Potential publication bias was assessed with funnel plots using software Stata/MP 13.0. RESULTS: Twenty-six articles comprising 5063 patients were included in our NMA, which showed that postoperative hypocalcemia (or hypoparathyroidism) occurred more frequently in tPTX than in sPTX (OR = 3.50, 95% CI 1.10-11.0) or tPTX+AT patients (OR = 1.80, 95% CI 0.66-5.20). Regarding postoperative hypocalcemia (or hypoparathyroidism), there was no significant difference between sPTX and tPTX+AT (OR = 0.53, 95% CI 0.24-1.10). As for recurrence rates, statistically significant differences were observed between sPTX and tPTX (OR = 25.0, 95% CI 5.1-260), tPTX+AT and tPTX (OR = 20.0, 95% CI 4.2-200), and sPTX and tPTX+AT (OR = 1.30, 95% CI 0.65-2.50). Regarding reoperation rates, sPTX experienced higher incidence compared with tPTX+AT (OR = 1.20, 95% CI 0.53-2.70) or tPTX patients (OR = 2.70, 95% CI 1.20-14.00). CONCLUSIONS: TPTX+AT is recommended as the most efficient and safe surgical SHPT treatment with minimal adverse effects. Large-scale randomized controlled trials are recommended to confirm the NMA results.

Transoral endoscopic selective lateral neck dissection for papillary thyroid carcinoma: a pilot study.

BACKGROUND: Transoral endoscopic thyroid surgery via the vestibular approach (TOETVA) has been gradually accepted worldwide due to its scar-free effect on the neck. Even central cervical lymphadenectomy has been performed in some cases of papillary thyroid carcinoma (PTC). However, there are few reports involving lateral neck dissection with TOETVA. In this study, we attempted to perform selective lateral neck dissection (SLND) for PTC via a transoral vestibular approach. METHODS: This prospective study was conducted from January 2016 to December 2018 in twenty PTC patients with unilateral T1 tumors without capsular invasion and patients with abnormal level III and IV lymph nodes who underwent SLND via a transoral vestibular approach. RESULTS: Endoscopic surgery was successfully accomplished in all 20 PTC patients. The mean age was 29.2 ± 5.5 (20-41) years. The mean operation time was 146.0 ± 18.7 (114-193) min. The average postoperative hospital stay was 6.8 ± 1.3 (5-10) days. The mean number of removed nodes was 7.4 ± 2.5 (4-12) in the central neck and 10.9 ± 2.8 (6-16) in the lateral neck, and the positive yield amounts were 2.0 ± 1.2 (0-4) and 2.7 ± 1.9 (0-6), respectively. No major complications occurred except for 1 case of transient unilateral recurrent laryngeal nerve palsy and two cases of effusion in the operative area. No evidence of persistent or recurrent disease was observed in these patients during a mean follow-up of 24.3 ± 9.1 (6-36) months. The cosmetic results and protection of personal privacy of this procedure were excellent. CONCLUSION: Endoscopic SLND via the transoral vestibular approach is feasible, safe, and effective for selected PTCs. A multicenter large comparative study is necessary.

Risk factors of metastasis to the lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma.

PURPOSE: To investigate the risk factors of lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in papillary thyroid carcinoma. METHODS: Clinicopathologic feature data of 427 patients with right or double lobes who underwent surgery between January 2014 to August 2019 in the Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, were retrospectively analyzed. The risk factors of LN-prRLN metastasis were analyzed by the Chi-squared test and multivariate logistic regression. RESULTS: LN-prRLN metastasis was detected in 96 patients. Univariate analysis showed that age, right-side tumor diameter, capsular invasion, comorbid adenoma, and VIa compartment LN metastasis were significantly associated with LN-prRLN metastasis (all P < 0.05). Multivariate logistic regression analysis showed that right-side tumor diameter, capsular invasion, and VIa compartment LN metastasis were independent risk factors of LN-prRLN metastasis (all P ≤ 0.001). The receiver operating characteristic curve showed that the cutoff value of the right tumor diameter for predicting LN-prRLN metastasis was 1.25 cm (sensitivity = 0.5, specificity = 0.819, area under the curve = 0.720, P < 0.001). CONCLUSION: The incidence of LN-prRLN metastasis cannot be ignored, and our findings indicate that prophylactic LN-prRLN dissection should be performed in patients with right-side tumor diameter ≥ 1.25 cm, capsular invasion, and VIa compartment LN metastasis.

[Application of microscopic spectroscopy in quality control of Niuhuang Qingxin pills].

Application of microscopic spectroscopy in quality control of Niuhuang Qingxin pills was discussed. First, microscopic characteristics specified by the statutory standard of Niuhuang Qingxin pills were summarized. Then new identification method was established for Dioscoreae Rhizoma, Saigae Tataricae Cornu, Cinnamomi Cortex and Saposhnikoviae Radix. Finally, microscopic spectroscopy was used for test of Dioscoreae Rhizoma's adulterant Dioscoreae Fordii Rhizoma.It was the first time for this technology being applied in adulteration test of Chinese patent medicine.The results showed that Saigae Tataricae Cornu was not detected in 2 batches of Niuhuang Qingxin pills from 1 manufacturer while Dioscoreae Fordii Rhizoma was detected in 3 batches of samples from 2 manufacturers. The proposed methods were accurate, simple, rapid, objective and economic, which offered a more comprehensive approach for quality control of Niuhuang Qingxin pills. It was indicated that conventional technology such as microscopic spectroscopy could play an important role in identification of traditional Chinese medicine whose index ingredient was deficient or tiny.