The role of intraoperative central lymph node biopsy in the treatment of clinically low-risk PTMC.

PURPOSE: To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative nodes (cN0) papillary thyroid microcarcinoma (PTMC) without extra-glandular invasion. METHODS: The clinical data of 465 patients were collected retrospectively. Part of prelaryngeal, pretracheal and ipsilateral paratracheal lymph nodes were taken for frozen pathological examination during the operation. Then the thyroid lobe on the tumor side and isthmus were excised, and central neck dissection of the affected side was performed in all patients. The number of metastases in entire central lymph nodes of the affected side can be obtained by postoperative paraffin pathology. If the number of positive lymph nodes during surgery is ≥3, contralateral gland resection was performed. RESULTS: In this group of 465 patients, there were 186 cases with central lymph node metastasis. The Kappa coefficient of consistency between frozen pathology and paraffin pathology in central lymph nodes was 0.605. The ROC curve for the number of intraoperative frozen metastases-postoperative pathological metastases over 5 showed that the AUC of the curve was 0.793, while the maximum Youden index was 0.5259, whose corresponding number of positive lymph nodes was 3. CONCLUSION: Intraoperative central lymph nodes biopsy can be used as an important indicator for the status of central lymph node metastasis in unilateral cN0 PTMC patients without extra-glandular invasion and a determinant for central lymph node dissection. While the number of positive lymph nodes intraoperatively is ≥3, total thyroidectomy should be considered.

Neoadjuvant therapy increases the risk of metabolic disorders and osteosarcopenia in patients with early breast cancer.

BACKGROUND: The purpose of this study is to evaluate the effects of neoadjuvant therapy on glucose and lipid metabolism, bone mineral density (BMD) and muscle, and to explore the relationship between metabolic disorders and changes in body composition, so as to provide better health management strategies for breast cancer survivors. METHODS: The clinical data of 43 patients with breast cancer who received neoadjuvant therapy in Xuanwu Hospital from January 2020 to June 2021 were analyzed retrospectively. The biochemical results, including albumin, blood glucose, triglyceride and cholesterol, were collected before neoadjuvant therapy and before surgery. The pectoral muscle area, pectoral muscle density and cancellous bone mineral density of the 12th thoracic vertebra were also measured by chest CT. RESULTS: After neoadjuvant therapy, fasting blood glucose, triglyceride and cholesterol were significantly increased, albumin was decreased. At the same time, pectoral muscle area, pectoral muscle density and T12 BMD were decreased. After treatment, BMD was positively correlated with pectoral muscle area, R2 = 0.319, P = 0.037, and BMD was also positively correlated with pectoral muscle density, R2 = 0.329, P = 0.031. Multivariate analysis showed that BMD and pectoral muscle density were correlated with menstrual status, and pectoral muscle area was correlated with body mass index before treatment, none of which was related to glucose and lipid metabolism. CONCLUSION: Neoadjuvant therapy can cause glucose and lipid metabolism disorder, BMD decrease and muscle reduction. BMD was positively correlated with muscle area and density after treatment, suggesting that patients had an increased chance of developing osteosarcopenia.

Elevated MMP1 Expression in Carcinoma-Associated Fibroblasts of Breast Cancer Contributes to Tumor Progression and Unfavorable Prognosis.

OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer. METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments. RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment. CONCLUSION: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.

In vitro differentiation of human CD45+ CD34+ induced hematopoietic progenitor cells from iPSCs using a monolayer system.

Hematopoietic stem cells (HSCs) represent crucial target cells in the management of hematopoietic and immune system disorders. Unfortunately, the primary source of hematopoietic stem cells is limited. Hematopoietic stem cells derived from induced pluripotent stem cells (iPSCs) hold great promise for applications in cell therapy, disease modeling, and drug screening. To achieve a consistent induction method, one specific induction scheme capable of reliably generating CD34 and CD45 double-positive cells from iPSCs was optimized, employing a comparative analysis and screening of various induction methods. The comprehensive induction procedures are outlined in this document.

Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non-G-CIMP glioblastomas with unmethylated MGMT promoter: MGMT-dependent roles of GPR81.

PURPOSES: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT). METHODS: The discovery-validation approach was planned incorporating a series of G-CIMP-/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. RESULTS: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP-/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. CONCLUSIONS: The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP-/unMGMT GBMs.

Assessment of the prevalence and related factors of financial toxicity in cancer patients based on the COST scale: A systematic review and meta-analysis.

PURPOSE: The high cost of cancer treatment exposes patients to financial toxicity during treatment; however, no study has comprehensively analyzed the incidence of financial toxicity using a validated assessment tool. In this study, the objective was to ascertain the incidence of financial toxicity in cancer patients and the factors influencing it. METHODS: Nine electronic databases were retrieved to collect cross-sectional studies reporting financial toxicity in cancer patients. A random effects meta-analysis was applied to yield the overall prevalence of financial toxicity. Subgroup analyses were conducted depending on the factors affecting financial toxicity. RESULTS: In total, 30 studies met our inclusion criteria. The pooled prevalence of financial toxicity in cancer patients was 48% (95%CI:38%-58%, I2 = 99.4%, p < 0.001). In the subgroup analysis, a higher prevalence of financial toxicity in patients aged <67 years (47%, 95%CI: 28%-66%, I2 = 97.5%, p < 0.001), female (46%, 95%CI:39%-53%, I2 = 94.9%,p < 0.001), lung cancer(57%, 95%CI:38%-75%, I2 = 96.9%, p < 0.001), developing countries (64%, 95%CI:55%-72%, I2 = 98.1%, p < 0.001), time of investigation following COVID-19 (53%, 95%CI:37%-69%, I2 = 99.4%, p < 0.001). CONCLUSION: Financial toxicity is prevalent in cancer patients and is increasingly evident after COVID-19. Furthermore, the odds of financial toxicity are higher in patients who are female, younger, whose cancer type is lung cancer, and from developing countries. These findings emphasize the significance of evaluating financial toxicity in cancer patients after COVID-19, especially in developing countries. This may play a pivotal role in helping patients cope with financial toxicity.

A closed-loop catalytic nanoreactor system on a transistor.

Precision chemistry demands miniaturized catalytic systems for sophisticated reactions with well-defined pathways. An ideal solution is to construct a nanoreactor system functioning as a chemistry laboratory to execute a full chemical process with molecular precision. However, existing nanoscale catalytic systems fail to in situ control reaction kinetics in a closed-loop manner, lacking the precision toward ultimate reaction efficiency. We find an inter-electrochemical gating effect when operating DNA framework-constructed enzyme cascade nanoreactors on a transistor, enabling in situ closed-loop reaction monitoring and modulation electrically. Therefore, a comprehensive system is developed, encapsulating nanoreactors, analyzers, and modulators, where the gate potential modulates enzyme activity and switches cascade reaction "ON" or "OFF." Such electric field-effect property enhances catalytic efficiency of enzyme by 343.4-fold and enables sensitive sarcosine assay for prostate cancer diagnoses, with a limit of detection five orders of magnitude lower than methodologies in clinical laboratory. By coupling with solid-state electronics, this work provides a perspective to construct intelligent nano-systems for precision chemistry.

Diagnostic value of preoperative examination for evaluating margin status in breast cancer.

BACKGROUND: A positive resection margin is a major risk factor for local breast cancer recurrence after breast-conserving surgery (BCS). Preoperative imaging examinations are frequently employed to assess the surgical margin. AIM: To investigate the role and value of preoperative imaging examinations [magnetic resonance imaging (MRI), molybdenum target, and ultrasound] in evaluating margins for BCS. METHODS: A retrospective study was conducted on 323 breast cancer patients who met the criteria for BCS and consented to the procedure from January 2014 to July 2021. The study gathered preoperative imaging data (MRI, ultrasound, and molybdenum target examination) and intraoperative and postoperative pathological information. Based on their BCS outcomes, patients were categorized into positive and negative margin groups. Subsequently, the patients were randomly split into a training set (226 patients, approximately 70%) and a validation set (97 patients, approximately 30%). The imaging and pathological information was analyzed and summarized using R software. Non-conditional logistic regression and LASSO regression were conducted in the validation set to identify factors that might influence the failure of BCS. A column chart was generated and applied to the validation set to examine the relationship between pathological margin range and prognosis. This study aims to identify the risk factors associated with failure in BCS. RESULTS: The multivariate non-conditional logistic regression analysis demonstrated that various factors raise the risk of positive margins following BCS. These factors comprise non-mass enhancement (NME) on dynamic contrast-enhanced MRI, multiple focal vascular signs around the lesion on MRI, tumor size exceeding 2 cm, type III time-signal intensity curve, indistinct margins on molybdenum target examination, unclear margins on ultrasound examination, and estrogen receptor (ER) positivity in immunohistochemistry. LASSO regression was additionally employed in this study to identify four predictive factors for the model: ER, molybdenum target tumor type (MT Xmd Shape), maximum intensity projection imaging feature, and lesion type on MRI. The model constructed with these predictive factors exhibited strong consistency with the real-world scenario in both the training set and validation set. Particularly, the outcomes of the column chart model accurately predicted the likelihood of positive margins in BCS. CONCLUSION: The proposed column chart model effectively predicts the success of BCS for breast cancer. The model utilizes preoperative ultrasound, molybdenum target, MRI, and core needle biopsy pathology evaluation results, all of which align with the real-world scenario. Hence, our model can offer dependable guidance for clinical decision-making concerning BCS.

A nomogram for intraoperatively predicting non-sentinel lymph node metastases in early breast cancer patients with positive sentinel lymph nodes.

Background: Individualized decisions are required in early-stage breast cancer patients. We aimed to establish a novel model for predicting non-sentinel lymph node (SLN) metastases in patients with positive SLNs, using preoperative and intraoperative characteristics and inflammatory indicators. Methods: The data of 489 patients with invasive breast cancer were retrospectively collected from Xuanwu Hospital between 2014 and 2021. Among them, 96 patients with at least one positive SLN were used to build the predictive model. Univariate and multivariate analyses were performed to identify the risk factors of non-SLN metastases. A nomogram was developed using these risk factors and was validated by calibration curves. The area under the receiver operating characteristics curve (AUC) and decision curve analyses (DCA) were used to compare our novel nomogram with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Cross-validation was performed for further internal validation of the predictive model. External validation was conducted using another treatment group (n=46 patients) in Xuanwu Hospital. Results: Non-SLN metastases occurred in 42 of the 83 patients with positive SLNs (50.6%). Multivariate stepwise logistic regression indicated that the risk factors were age (P=0.032), number of positive SLNs (P=0.020), number of negative SLNs (P=0.011), resected tumor size (P=0.038), and monocyte count (P=0.012). A predictive model was developed and virtualized by nomogram using these five risk factors. The AUC of our nomogram was 0.867, which was significantly higher than that of the MSKCC model. DCA also showed a superior clinical value for our novel nomogram. After 10-fold cross-validation with 400 times repetitions, the AUC of our model was still 0.830. External validation of our model showed an AUC of 0.727. The model was well-calibrated in the internal and external validation series. Conclusions: A five-factor nomogram was developed for predicting non-SLN metastases in early-stage breast cancer patients. This novel tool exhibited good accuracy and could assist clinicians with intraoperative decisions in breast cancer patients with positive SLNs.

Phase III study of HR-positive/HER2-negative/lymph node-positive breast cancer non-responsive to primary chemotherapy: a randomized trial.

There are few studies focus on post-neoadjuvant treatment in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-positive (LN+) breast cancer, a multi-center, open-label, randomized, controlled phase III trial was conducted to evaluate pathological response-guided non-cross-resistant adjuvant chemotherapy in patients with HR+/HER2-/LN+ breast cancer who were non-responsive to primary chemotherapy. Patients received four cycles of non-cross-resistant adjuvant chemotherapy plus endocrine therapy (ET), or ET alone. Forty patients responsive to neoadjuvant chemotherapy and with Miller and Payne G4 or G5 and LN- status were assigned to the observation group. Distant disease-free survival was the primary endpoint. The final intention-to-treat analysis comprised 379 patients. After a median follow-up period of 72.4 months, the 5-year distant disease-free survival was 92% and 90% in the chemotherapy plus ET and ET-alone groups, respectively. Comparatively, the observation group showed a trend towards better distant disease-free survival. For patients non-responsive to neoadjuvant chemotherapy, adjuvant non-cross-resistant chemotherapy did not significantly improve distant disease-free survival compared to ET alone.

Factors related to quality of life after video-assisted thoracoscopic surgery in patients with stage I adenocarcinoma lung cancer: A longitudinal study.

PURPOSE: This study aimed to assess the 5-year survival, quality of life for cancer- and lung-specific symptoms, and to identify predictive factors of quality of life during a 12-month period after video-assisted thoracic surgery (VATS) for early-stage lung adenocarcinoma. METHODS: A convenience sample of 53 patients who had undergone VATS for lung cancer was used for this longitudinal, prospective study. All participants provided responses to the cancer-specific quality-of-life European Organization for Research and Treatment of Cancer questionnaire as well as a questionnaire for lung cancer-specific symptoms using structured interviews at baseline (T0) and 3-, 6-, 9-, and 12-months post-surgery (T1, T2, T3, and T4, respectively). Generalized estimating equation models were used to investigate whether quality of life scores improved from baseline measures and to determine characteristics associated with changes in scores for quality-of-life post-surgery. RESULTS: The mean age of participants was 58.5 years (SD = 8.76), and most were female (64.2%). Participants received either a wedge or sublobular lobectomy (47.2%) or a lobectomy (52.8%). The size of the primary tumour for most participants was <2 cm (78.7%). The five-year survival rate was 90%. Lung-specific symptoms of insomnia were worse at T1 compared with baseline. Significant improvements in scores for function and cancer symptoms were seen at T4 compared with scores at T0. Age, marital status, smoking, alcohol consumption, and a history of previous cancer were significantly associated with quality of life. CONCLUSIONS: Surgical resection with VATS resulted in good 5-year survival rates and long-term improvements in quality of life. Our findings suggest VATS for patients with early-stage lung adenocarcinoma should be considered as a means of improving long-term survival and quality of life.

The impact of symptom distress on health-related quality of life in liver cancer patients receiving arterial chemoembolization: the mediating role of hope.

BACKGROUND: Trans-hepatic arterial chemoembolization (TACE) is a treatment option for liver cancer patients. It can prolong patients' survival but can also cause symptom distress. Symptom distress (SDs) can directly impact quality of life (QOL) and may indirectly influence QOL by lessening hope. In this study, we wanted to explore the mediating effect of hope on the relationship between SDs and QOL among patients with liver cancer receiving TACE. METHODS: A cross-sectional study was conducted from December 20, 2017, to August 6, 2018, at a gastroenterology ward of a medical center. The participants were 92 liver cancer patients (69.6% male, mean age 67.8) who were admitted for TACE treatment. Information on SDs, hope, and QOL was collected by questionnaire on discharge day. Hayes' PROCESS model was used to test the mediating effect of hope on the relationship between SDs and QOL. RESULTS: The mean score and standard deviation (SD) of SDs, hope, and QOL were 32.08 (SD = 6.22), 27.09 (SD = 3.51), and 55.16 (SD = 17.33), respectively. SDs negatively impacts quality of life. The total effect of SDs on QOL was - 1.41 (95% confidence interval [CI]: - 1.96, - 0.86). The indirect effect via the mediation of hope was - 0.95 (95% CI: - 1.7, - 0.45). Hope partially mediated the effect of SDs on QOL. CONCLUSION: SDs after TACE is vital; it directly reduces a patient's overall QOL and can indirectly hinder it by reducing the patient's hope. In addition to symptom management, interventions that help patients maintain their hope are key to improving QOL among patients receiving TACE.

Accidental venous port placement via the persistent left superior vena cava: Two case reports.

BACKGROUND: Breast cancer poses a great threat to females worldwide. There are various therapies available to cure this common disease, such as surgery, chemotherapy, radiotherapy, and immunotherapy. Implantable venous access ports (IVAP, referred to as PORT) have been widely used for breast cancer chemotherapy. Venous malformations are possible conditions encountered during PORT implantation. Persistent left superior vena cava (PLSVC) is a common superior vena cava malformation. Most patients have normal right superior vena cava without affecting hemodynamics, so patients often have no obvious symptoms. CASE SUMMARY: We incidentally found that two patients had PLSVC while a PORT was implanted via the internal jugular vein. Due to chemotherapy for breast cancer, PORT was successfully implanted under the guidance of ultrasound into these 2 patients. Positive chest X-ray examination after the operation showed that the catheter ran beside the left mediastinum and the end was located in the seventh thoracic vertebra. The patients had no catheter-related complications and successfully completed the course of chemotherapy. Ultrasonography found that the ratio of PORT outer diameter to PLSVC inner diameter was less than 0.45, which was in line with the recommendations of relevant literature and operating guidelines. The purpose of this article is to introduce two rare cases and review the relevant literature. CONCLUSION: Correct assessment of PLSVC status and ultrasound-guided PORT placement generally does not affect breast cancer patients chemotherapy.

Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) can be differentiated into osteoblasts and adipocytes. During these processes, super enhancers (SEs) play important roles. Here, we performed comprehensive characterization of the SEs changes associated with adipogenic and osteogenic differentiation of hMSCs, and revealed that SEs changed more dramatically compared with typical enhancers. We identified a set of lineage-selective SEs, whose target genes were enriched with cell type-specific functions. Functional experiments in lineage-selective SEs demonstrated their specific roles in directed differentiation of hMSCs. We also found that some key transcription factors regulated by lineage-selective SEs could form core regulatory circuitry (CRC) to regulate each other's expression and control the hMSCs fate determination. In addition, we found that GWAS SNPs of osteoporosis and obesity were significantly enriched in osteoblasts-selective SEs or adipocytes-selective SEs, respectively. Taken together, our studies unveiled important roles of lineage-selective SEs in hMSCs differentiation into osteoblasts and adipocytes.

Changes of Tumor Markers in Patients with Breast Cancer during Postoperative Adjuvant Chemotherapy.

Objective: Serum tumor marker (STM) elevation can detect metastasis earlier than imaging diagnosis and, although not recommended by guidelines, is still widely used in clinical practice for postoperative follow-up of breast cancer patients. The purpose of this study was to investigate the change rules of CEA and CA153 in patients with HER2-negative breast cancer during postoperative adjuvant chemotherapy and their influencing factors. Materials and Methods: The medical records of patients with HER2-negative early breast cancer who visited Xuanwu Hospital from September 2018 to June 2021 were retrospectively analyzed. Demographic characteristics and baseline data of CEA and CA153 at initial diagnosis were collected. Data of CEA, CA153, biochemistry (including ALT, AST, rGT, triglycerides, cholesterol, and blood glucose) and blood routine (including white blood cells, neutrophils, monocytes, lymphocytes, and platelets) were also collected before chemotherapy, at the end of chemotherapy and more than 3 months after the end of chemotherapy. LY/MONO, NEUT/LY, PLT/LY, and systemic immune inflammation index (SII) were calculated and statistically analyzed using SPSSAU software. Results: A total of 90 patients were enrolled, all of whom were female, with a mean age of 55.11 ± 10.60 y. The value of CEA at initial diagnosis was 2.10 ± 1.11 ng/mL, and high expression was mostly correlated with past history of chronic diseases and tumor lymph node metastasis; the value of CA153 was 11.80 ± 6.60 U/mL, and high expression was correlated with high SII at initial diagnosis. Surgery did not affect the values of serum CEA and CA153. At the end of chemotherapy, CEA and CA153 were 2.68 ± 1.34 ng/mL and 18.51 ± 8.50 U/mL, respectively, which were significantly increased compared with those before chemotherapy, and were linearly correlated with the values before chemotherapy. They decreased (CEA 2.45 ± 1.19 ng/mL, CA153 10.87 ± 5.96 U/mL) again three months after the end of chemotherapy, manifested as "spiking" phenomenon, which was associated with lymph node metastasis at diagnosis, body metabolic disorders, and chronic inflammatory status. Conclusion: CEA and CA153 were increased presenting as "spiking" phenomena in patients with early HER2-negative breast cancer during postoperative adjuvant chemotherapy, and the peak of increase was linearly correlated with the indicators before chemotherapy. Clinical attention should be paid to this change to avoid excessive diagnosis and treatment leading to medical resource consumption.

A Nomogram Based on Clinicopathological and Ultrasound Imaging Characteristics for Predicting Cervical Lymph Node Metastasis in cN0 Unilateral Papillary Thyroid Microcarcinoma.

Objective: The aim of this study was to establish a practical nomogram for preoperatively predicting the possibility of cervical lymph node metastasis (CLNM) based on clinicopathological and ultrasound (US) imaging characteristics in patients with clinically node-negative (cN0) unilateral papillary thyroid microcarcinoma (PTMC) in order to determine a personal surgical volume and therapeutic strategy. Methods: A total of 269 consecutive patients diagnosed with cN0 unilateral PTMC by postoperative pathological examination from January 2018 to December 2020 were retrospectively analyzed. All the patients underwent lobectomy or thyroidectomy with routine prophylactic central lymph node dissection (CLND) and were divided into a CLNM group and a non-CLNM group. Using logistic regression, the least absolute shrinkage and selection operator (LASSO) regression analysis was applied to determine the risk factors for CLNM in patients with unilateral cN0 PTMC. A nomogram including risk-factor screening using LASSO regression for predicting the CLNM in patients with cN0 unilateral PTMC was further developed and validated. Results: Risk factors identified by LASSO regression, including age, sex, tumor size, presence of extrathyroidal extension (ETE), tumor diameter/lobe thickness (D/T), tumor location, and coexistent benign lesions, were potential predictors for CLNM in patients with cN0 unilateral PTMC. Meanwhile, age (odds ratio [OR] = 0.261, 95% CI.104-0.605; P = 0.003), sex (men: OR = 3.866; 95% CI 1.758-8.880; P < 0.001), ETE (OR = 3.821; 95% CI 1.168-13.861; P = 0.032), D/T (OR = 72.411; 95% CI 5.483-1212.497; P < 0.001), and coexistent benign lesions (OR = 3.112 95% CI 1.407-7.303; P = 0.007) were shown to be significantly related to CLNM by multivariant logistic regression. A nomogram for predicting CLNM in patients with cN0 unilateral PTMC was established based on the risk factors identified by the LASSO regression analysis. The receiver operating characteristic (ROC) curve for predicting CLNM by nomogram showed that the area under the curve (AUC) was 0.777 and exhibited an excellent consistency. Conclusions: A nomogram based on clinical and US imaging characteristics for predicting the probability of CLNM in patients with cN0 unilateral PTMC was developed, which showed a favorable predictive value and consistency. Further prospective research to observe the oncological outcomes is necessary to determine whether the nomogram could potentially guide a personalized surgical volume and surgical approach.

Metabolomics Identifies Biomarker Signatures to Differentiate Pancreatic Cancer from Type 2 Diabetes Mellitus in Early Diagnosis.

METHODS: Plasma metabolic profiles in 26 PC patients, 27 DM patients, and 23 healthy volunteers were examined using an ultraperformance liquid chromatography coupled with tandem mass spectrometry platform. Differential metabolite ions were then identified using the principal component analysis (PCA) model and the orthogonal partial least-squares discrimination analysis (OPLS-DA) model. The diagnosis performance of metabolite biomarkers was validated by logistic regression models. RESULTS: We established a PCA model (R2X = 23.5%, Q2 = 8.21%) and an OPLS-DA model (R2X = 70.0%, R2Y = 84.9%, Q2 = 69.7%). LysoPC (16 : 0), catelaidic acid, cerebronic acid, nonadecanetriol, and asparaginyl-histidine were found to identify PC, with a sensitivity of 89% and a specificity of 91%. Besides, lysoPC (16 : 0), lysoPC (16 : 1), lysoPC (22 : 6), and lysoPC (20 : 3) were found to differentiate PC from DM, with higher accuracy (68% versus 55%) and higher AUC values (72% versus 63%) than those of CA19-9. The diagnostic performance of metabolite biomarkers was finally validated by logistic regression models. CONCLUSION: We succeeded in screening differential metabolite ions among PC and DM patients and healthy individuals, thus providing a preliminary basis for screening the biomarkers for the early diagnosis of PC.

Development and validation of a novel 14-gene signature for predicting lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: There is still no reasonably accurate method of preoperatively predicting central lymph node metastasis (LNM), and it is essential to develop an effective evaluation model for predicting LNM in papillary thyroid carcinoma (PTC) patients. METHODS: PTC samples were collected from The Cancer Genome Atlas database. Candidate genes were identified as continuously upregulated or downregulated genes in the process of N0 to N1a and N1a to N1b. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct the predictive model for LNM. Multivariate logistic regression analysis was performed to screen the potential factors related to LNM, and a nomogram was established. The risk score of the gene signature model for predicting disease-free survival (DFS) was evaluated by Kaplan-Meier analysis. RESULTS: A 14-gene signature was developed by LASSO regression for predicting LNM based on 69 differential expression genes (DEGs) that were continuously upregulated or downregulated in the progress of PTC. The receiver operating characteristic (ROC) curves of the 14-gene signature predicting LNM, central LNM and lateral LNM were generated. The area under the ROC (AUC) values were 0.806 [95% confidence interval (CI): 0.7608-0.8815], 0.755 (95% CI: 0.6839-0.8263) and 0.821 (95% CI: 0.7608-0.8815). The nomogram's C-index value, including the 14-gene signature and other potential risk factors, was 0.786 (95% CI: 0.7296-0.8425), and the calibration exhibited fairly good consistency with the perfect prediction. Based on the 14-gene risk score, high-risk PTC patients had a worse DFS. CONCLUSIONS: A novel 14-gene signature was developed for predicting LNM in PTC patients. The risk score also correlated with DFS in PTC patients.