Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology.

Background: Papillary thyroid cancer (PTC) is the most common pathological type of thyroid cancer with a high incidence globally. Increasing evidence reported that fibroblasts infiltration in cancer was correlated with prognostic outcomes. However, fibroblasts related study in thyroid cancer remains deficient. Methods: Single-cell sequencing data of PTC were analyzed by Seurat R package to explore the ecosystem in PTC and identify fibroblasts cluster. The expression profiles and prognostic values of fibroblast related genes were assessed in TCGA dataset. A fibrosis score model was established for prognosis prediction in thyroid cancer patients. Differentially expressed genes and functional enrichment between high and low fibrosis score groups in TCGA dataset were screened. The correlation of immune cells infiltration and fibrosis score in thyroid cancer patients was explored. Expression levels and prognostic values of key fibroblast related factor were validated in clinical tissues another PTC cohort. Results: Fibroblasts were highly infiltrated in PTC and could interact with other type of cells by single-cell data analysis. 34 fibroblast related terms were differentially expressed in thyroid tumor tissues. COX regression analysis suggested that the constructed fibrosis score model was an independent prognostic predictor for thyroid cancer patients (HR = 5.17, 95%CI 2.31-11.56, P = 6.36E-05). Patients with low fibrosis scores were associated with a significantly better overall survival (OS) than those with high fibrosis scores in TCGA dataset (P = 7.659E-04). Specific immune cells infiltration levels were positively correlated with fibrosis score, including monocytes, M1 macrophages and eosinophils. Conclusion: Our research demonstrated a comprehensive horizon of fibroblasts features in thyroid cancer microenvironment, which may provide potential value for thyroid cancer treatment.

Identification of Six N7-Methylguanosine-Related miRNA Signatures to Predict the Overall Survival and Immune Landscape of Triple-Negative Breast Cancer through In Silico Analysis.

Triple-negative breast cancer (TNBC) is a widely prevalent breast cancer, with a mortality rate of up to 25%. TNBC has a lower survival rate, and the significance of N7-methylguanosine (m7G) modification in TNBC remains unclear. Thus, this study is aimed at investigating m7G-related miRNAs in TNBC patients through in silico analysis. In our research, RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. The miRNAs targeting typical m7G modification regulators Methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4) were predicted on the TargetScan website. A miRNA risk model was built, and its prognostic value was evaluated by R soft packages. Single-sample gene set enrichment analysis was used to assess immune infiltration, and further expression of immune checkpoints was investigated. As a result, miR-421, miR-5001-3p, miR-4326, miR-1915-3p, miR-3177-5p, and miR-4505 were identified to create the risk model. A nomogram consisting of the stage N and risk model predicted overall survival effectively among TNBC patients. Treg and TIL were shown to be strongly linked to the risk model, and the high-risk group had higher levels of four immune checkpoints expression (CD28, CTLA-4, ICOS, and TNFRSF9). A risk model consisting of m7G-related miRNAs was constructed. The findings of the current study could be used as a prognostic biomarker and can provide a novel immunotherapy insight for TNBC patients.

Clinicopathologic predictors of central lymph node metastases in clinical node-negative papillary thyroid microcarcinoma: a systematic review and meta-analysis.

BACKGROUND: The presence of central lymph node metastases (CLNM) has been suggested as a risk factor for poorer prognosis and recurrence in papillary thyroid microcarcinoma (PTMC). However, the clinicopathologic factors for CLNM in clinical node-negative (CN0) PTMC were not well defined. This study aimed to perform a systematic review and meta-analysis to investigate the significant clinicopathologic predictors of CLNM in CN0 PTMC. METHODS: A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science. Case-control studies on the association of clinicopathologic risk factors with CLNM in CN0 PTMC were included. RESULTS: Thirteen eligible studies involving 6068 patients with CN0 PTMC were included. From the pooled analyses, male (odds ratio [OR]: 2.07, 95% CI: 1.49-2.87, P < 0.001), multifocality (OR: 1.88, 95% CI: 1.54-2.29, P < 0.001), tumor size > 5 mm (OR: 1.84, 95% CI: 1.55-2.18, P < 0.001), and extrathyroidal extension (OR: 1.96, 95% CI: 1.30-2.95, P = 0.001) are significantly associated with increased risk of CLNM in CN0 PTMC. A sample size with a cutoff point of 200 was identified as the source of heterogeneity for sex according to meta-regression (t = 3.18, P = 0.033). Then, the subgroup analysis of male was performed, which illustrated that male increased the risk of CLNM in the small sample group (SG) and the large sample group (LG) by 6.11-folds and 2.01-folds, respectively (SG: OR, 6.11, 95% CI, 3.16-11.81, P < 0.001; LG: OR, 2.01, 95% CI, 1.65-2.46, P < 0.001). CONCLUSIONS: Male, multifocality, tumor size > 5 mm, and extrathyroidal extension may be reliable clinical predictors of CLNM in CN0 PTMC. Moreover, prophylactic central lymph node dissection should be considered in surgical decision-making for CN0 PTMC patients, who are male, multifocal, with tumor size > 5 mm, and with extrathyroidal extension. TRIAL REGISTRATION: CRD42021242211 (PROSPERO).

Comparison of Great Curvature Plication with Duodenal-Jejunal Bypass (GCP-DJB) and Sleeve Gastrectomy (SG) on Metabolic Indices and Gut Hormones in Type 2 Diabetes Mellitus Rats.

OBJECTIVE: The present study compared the therapeutic effects of great curvature plication with duodenal-jejunal bypass (GCP-DJB) and the commonly used sleeve gastrectomy (SG) in rats with type 2 diabetes mellitus (T2DM). METHODS: The rats were randomly divided into three groups: Control group (n = 6), SG group (n = 6), and GCP-DJB group (n = 6). Body weight, daily food intake, fasting blood glucose level, fasting insulin level, insulin resistance index, and fasting serum concentrations of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and bile acid were measured. In addition, postoperative changes in body weight and daily food intake at 2, 4, 6, 8, 10, and 12 weeks were also recorded. At week 12, an oral glucose tolerance test (OGTT) and insulin release test were performed to determine glucose tolerance. The insulin resistance index (IRI) was also measured. The postprandial secretion curves and area under the curve (AUC) of GLP-1, gastric inhibitory polypeptide (GIP), PYY, and bile acid were also calculated. RESULTS: Before surgery, no significant differences in body weight, daily food intake, fasting blood glucose, fasting insulin, insulin resistance index, fasting GLP-1, PYY, and bile acid were found among the three groups (P > 0.05). At postoperative week 12, body weight and food intake in the SG and GCP-DJB groups were lower than those in the Control group (P < 0.05), and body weight in the GCP-DJB group was lowest (P < 0.05). Glucose tolerance, postprandial serum insulin (INS), GLP-1, PYY, and bile acid were significantly higher in the SG and GCP-DJB groups than in the Control group (P < 0.05). The parameters related to glucose metabolism in the GCP-DJB group were higher than those in the SG group with the exception of serum insulin (P < 0.05). In addition, IRI and GIP secretion were significantly lower in the SG and GCP-DJB groups than in the Control group (P < 0.05) and were lowest in the GCP-DJB group (P < 0.05). CONCLUSION: Both GCP-DJB and SG are surgical options for the treatment of T2DM. The underlying mechanism of these treatments may be related to the decrease in body weight, food intake, GIP, IRI, and the increase in INS, GLP-1, PYY, and bile acid. According to the various metabolic indicators related to the hypoglycemic effects in T2DM, GCP-DJB was superior to SG.

Greater Curvature Plication with Duodenal-Jejunal Bypass: a Novel Metabolic Surgery for Type 2 Diabetes Mellitus.

OBJECTIVE: The study investigated the use of great curvature plication with duodenal-jejunal bypass (GCP-DJB) in a type 2 diabetic with obesity rat model. METHODS: Twenty-two Sprague-Dawley rats were given a high fat and sugar diet with subsequent intraperitoneal injection of a small dosage of streptozotocin (30 mg/kg) and randomly assigned to either GCP-DJB (n = 12) or Sham surgery (n = 10). Body weight, peripheral blood glucose, and fasting serum insulin were assayed, and insulin resistance index (IRI) was calculated, before and at 1, 2, 4, and 8 weeks after surgery. RESULTS: No differences were found in the preoperative characteristics of the two groups (P > 0.05). At week 1, the body weights decreased significantly, but there was no significant difference between the two groups (P > 0.05).The fasting blood glucose was significantly lower in the GCP-DJB than in the Sham group (P < 0.05), serum insulin levels were higher (P < 0.05), and IRI began to decline (P < 0.05). From 2 to 8 weeks, the body weight of Sham group gradually recovered and continued to rise, while the GCP-DJB group remained at a relatively lower state. Compared to the Sham group, the body weight, fasting blood glucose as well as IRI of GCP-DJB rats had significantly decreased (P < 0.05). But, the fasting insulin concentrations had significantly increased (P < 0.05). CONCLUSION: This novel GCP-DJB procedure established a stable animal model for the study of metabolic surgery to treat type 2 diabetes mellitus (T2DM).

To assess the effects of parathyroidectomy (TPTX versus TPTX+AT) for Secondary Hyperparathyroidism in chronic renal failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Secondary Hyperparathyroidism (SHPT) requiring parathyroidectomy (PTX) occurs more commonly in patients with progressive chronic kidney disease and in those on long-term lithium therapy. Successful PTX often results in a dramatic drop of parathyroid hormone level, relieves the patient from clinical symptoms, and reduces mortality. However, there is an ongoing debate on the optimal surgical treatment of SHPT. Currently, no clinical guidelines or trials have definitely answered the question of whether Total Parathyroidectomy (TPTX) is superior or equal to Total Parathyroidectomy with Autotransplantation (TPTX + AT). OBJECTIVE: The aims of the study were to compare the efficacy of two different surgical procedures and to develop evidence-based practice guidelines for the treatment of SHPT. METHODS: Citations were identified in the Medline, Cochrane, EMBASE, and Chinese Biomedical Literature databases through November 2016. The Newcastle-Ottawa Scale (NOS) score was used to assess the methodological quality of the studies included. All data were analyzed using Review Manager 5.3. RESULTS: A total of nine cohort studies and one Randomized Controlled Trials (RCT), comprising 1283 patients, were identified. The NOS score of all the studies included was 5 or above. Compared with TPTX + AT, patients in the TPTX group had lower rates of "recurrence" (OR = 0.20; 95%CI, 0.11-0.38; P < 0.01), "recurrence or persistence" (OR = 0.18; 95%CI, 0.10-0.33; P < 0.01), "reoperation due to recurrence or persistence" (OR = 0.17; 95%CI, 0.06-0.54; P = 0.002), and shorter "operative time" (WMD = -17.30; 95%CI, -30.53 to -4.06; P < 0.05), except for a higher risk of "hypoparathyroidism" (OR = 2.97; 95%CI, 1.09-8.08; P = 0.01). However, none of the patients had developed permanent hypocalcemia or adynamic bone disease. No significant difference was found for "symptomatic improvement", "complications", "drug requirements", and "hospital stay" (P > 0.05). CONCLUSION: The findings indicate that TPTX is superior to TPTX + AT, while referring to the rate of recurrent SHPT. However, this conclusion needs to be tested in large-scale confirmatory trials. TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of refractory SHPT.