The tumor-nerve circuit in breast cancer.

It is well established that innervation is one of the updated hallmarks of cancer and that psychological stress promotes the initiation and progression of cancer. The breast tumor environment includes not only fibroblasts, adipocytes, endothelial cells, and lymphocytes but also neurons, which is increasingly discovered important in breast cancer progression. Peripheral nerves, especially sympathetic, parasympathetic, and sensory nerves, have been reported to play important but different roles in breast cancer. However, their roles in the breast cancer progression and treatment are still controversial. In addition, the brain is one of the favorite sites of breast cancer metastasis. In this review, we first summarize the innervation of breast cancer and its mechanism in regulating cancer growth and metastasis. Next, we summarize the neural-related molecular markers in breast cancer diagnosis and treatment. In addition, we review drugs and emerging technologies used to block the interactions between nerves and breast cancer. Finally, we discuss future research directions in this field. In conclusion, the further research in breast cancer and its interactions with innervated neurons or neurotransmitters is promising in the clinical management of breast cancer.

Contrast-enhanced ultrasound-guided sentinel lymph node biopsy in early-stage breast cancer: a prospective cohort study.

OBJECTIVE: This study evaluated the identification efficiency of contrast-enhanced ultrasound (CEUS) for sentinel lymph nodes (SLN) to accurately represent the axillary node status in early-stage breast cancer. METHOD: In total, 109 consecutive consenting patients with clinically node-negative and T1-2 breast cancer were included in this study. All patients received CEUS to identify SLN before surgery, and a guidewire was deployed to locate SLN in those who were successfully explored by CEUS. The patients underwent sentinel lymph node biopsy (SLNB), and the blue dye was used to trace SLN during the surgery. The decision to perform axillary lymph node dissection (ALND) depended on the intraoperative pathological identification of SLN by CEUS (CE-SLN). The concordance rate of pathological status between CE-SLN and dyed SLN was calculated. RESULT: The CEUS detection rate was 96.3%; CE-SLN failed in 4 patients. Among the remaining 105 successful identifications, 18 were CE-SLN positive by intraoperative frozen section, and one with CE-SLN micrometastasis was diagnosed by paraffin section. No additional lymph node metastases were found in CE-SLN-negative patients. The concordance rate of pathological status between CE-SLN and dyed SLN was 100%. CONCLUSION: CEUS can accurately represent the status of axillary lymph nodes in patients with clinically node-negative and small tumor burden breast cancer.

A prognostic eight-lncRNA expression signature in predicting recurrence of ER-positive breast cancer receiving endocrine therapy.

Long noncoding RNAs (lncRNAs) have the main role in the tumorigenesis of breast cancer. In the present study, lncRNA expression profiling was collected to identify a lncRNA expression signature from the Gene Expression Omnibus database. An eight-lncRNA signature was established to predict the survival of patients with estrogen receptor (ER)-positive breast cancer receiving endocrine therapy. Patients were separated into a low-risk group and a high-risk group based on this signature. Patients in high-risk group have worse survival compared to those in low-risk group using Kaplan-Meier curve analysis with log-rank test. Receiver operating characteristic analysis suggested good diagnostic efficiency of the eight-lncRNA signature. When adjusting the clinical features, including age, grade, lymph node status, and tumor size, this signature was independently associated with the relapse-free survival. The prognostic value of the lncRNA prognostic model was then validated in validation sets. When validated in a cohort of patients treated with neoadjuvant chemotherapy and endocrine therapy, this signature demonstrated good performance as well. Besides, we have built a nomogram that integrated the conventional clinicopathological features and the eight-lncRNA-based signature. To sum up, our results indicated that the eight-lncRNA prognostic model was a reliable tool to group patients at high and low risk of disease relapse. This signature may have possible implication in prognostic evaluations of patients with ER-positive breast cancer receiving endocrine therapy.

Weighted gene correlation network analysis identifies RSAD2, HERC5, and CCL8 as prognostic candidates for breast cancer.

As the most commonly diagnosed malignant tumor in female population, the prognosis of breast cancer is affected by complex gene interaction networks. In this research weighted gene co-expression network analysis (WGCNA) would be utilized to build a gene co-expression network to identify potential biomarkers for prediction the prognosis of patients with breast cancer. We downloaded GSE25065 from Gene Expression Omnibus database as the test set. GSE25055 and GSE42568 were utilized to validate findings in the research. Seven modules were established in the GSE25065 by utilizing average link hierarchical clustering. Three hub genes, RSAD2, HERC5, and CCL8 were screened out from the significant module (R 2 = 0.44), which were considerably interrelated to worse prognosis. Within test dataset GSE25065, RSAD2, and CCL8 were correlated with tumor stage, grade, and lymph node metastases, whereas HERC5 was correlated with lymph node metastases and tumor grade. In the validation dataset GSE25055 and RSAD2 expression was correlated with tumor grade, stage, and size, whereas HERC5 was related to tumor stage and tumor grade, and CCL8 was associated with tumor size and tumor grade. Multivariable survival analysis demonstrated that RSAD2, HERC5, and CCL8 were independent risk factors. In conclusion, the WGCNA analysis conducted in this study screened out novel prognostic biomarkers of breast cancer. Meanwhile, further in vivo and in vitro studies are required to make the clear molecular mechanisms.

A prognostic eight-gene expression signature for patients with breast cancer receiving adjuvant chemotherapy.

Breast cancer is a popularly diagnosed malignant tumor. Genomic profiling studies suggest that breast cancer is a disease with heterogeneity. Chemotherapy is one of the chief means to treat breast cancer, while its responses and clinical outcomes vary largely due to the conventional clinicopathological factors and inherent chemosensitivity of breast cancer. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, our study established a multi-mRNA-based signature model and constructed a relative nomogram in predicting distant-recurrence-free survival for patients receiving surgery and following chemotherapy. We constructed a signature of eight mRNAs (IPCEF1, SYNDIG1, TIGIT, SPESP1, C2CD4A, CLCA2, RLN2, and CCL19) with the LASSO model, which was employed to separate subjects into groups with high- and low-risk scores. Obvious differences of distant-recurrence-free survival were found between these two groups. This eight-mRNA-based signature was independently associated with the prognosis and had better prognostic value than classical clinicopathologic factors according to multivariate Cox regression results. Receiver operating characteristic results demonstrated excellent performance in diagnosing 3-year distant-recurrence by the eight-mRNA signature. A nomogram that combined both the eight-mRNA-based signature and clinicopathological risk factors was constructed. Comparing with an ideal model, the nomograms worked well both in the training and validation sets. Through the results that the eight-mRNA signature effectively classified patients into low- and high-risk of distant recurrence, we concluded that this eight-mRNA-based signature played a promising predictive role in prognosis and could be clinically applied in breast cancer patients receiving adjuvant chemotherapy.

Accuracy of CEUS-guided sentinel lymph node biopsy in early-stage breast cancer: a study review and meta-analysis.

OBJECTIVE: To investigate whether preoperative localization of sentinel lymph node (SLN) by contrast-enhanced ultrasound (CEUS) can further improve the accuracy of sentinel lymph node biopsy (SLNB). METHOD: Collect published literatures or conference reports by searching electronic databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) evaluation method is used to evaluate the quality of the screened literatures. The pooled risk ratio of cancer metastasis of SLN identified by CEUS (CE-SLN) compared with SLN not identified by CEUS (nonCE-SLN) is calculated, and the pooled diagnostic accuracy of CE-SLN for pathological status of all SLNs is also evaluated. RESULT: Through search and screening, a total of 16 studies were included, of which five and seven studies, respectively, entered the meta-analysis of metastatic risk ratio and diagnostic accuracy. The localization rate of preoperative CEUS for sentinel lymph nodes was 70 to 100%. The meta-analysis shows that the risk of metastasis of SLN identified by CEUS is significantly higher than that not identified by CEUS, 26.0% vs 4.6%, and risk ratio (RR) is 6.08 (95% CI 4.17-8.85). In early-stage breast cancer, the pathological status of CE-SLN is a good representative of all SLNs, with a pooled sensitivity of 98% (95% CI 0.94-1.00), pooled specificity of 100% (95% CI 0.99-1.00), diagnostic odds ratio (DOR) of 2153.18 (95% CI 476.53-9729.06), and area under the subject receiver operating characteristic (SROC) curve of 0.9968. CONCLUSION: In early-stage breast cancer, preoperative localization of SLN by CEUS is expected to further improve the accuracy of sentinel lymph node biopsy (SLNB).

An estrogen receptor (ER)-related signature in predicting prognosis of ER-positive breast cancer following endocrine treatment.

Quite a few estrogen receptor (ER)-positive breast cancer patients receiving endocrine therapy are at risk of disease recurrence and death. ER-related genes are involved in the progression and chemoresistance of breast cancer. In this study, we identified an ER-related gene signature that can predict the prognosis of ER-positive breast cancer patient receiving endocrine therapy. We collected RNA expression profiling from Gene Expression Omnibus database. An ER-related signature was developed to separate patients into high-risk and low-risk groups. Patients in the low-risk group had significantly better survival than those in the high-risk group. ROC analysis indicated that this signature exhibited good diagnostic efficiency for the 1-, 3- and 5-year disease-relapse events. Moreover, multivariate Cox regression analysis demonstrated that the ER-related signature was an independent risk factor when adjusting for several clinical signatures. The prognostic value of this signature was validated in the validation sets. In addition, a nomogram was built and the calibration plots analysis indicated the good performance of this nomogram. In conclusion, combining with ER status, our results demonstrated that the ER-related prognostic signature is a promising method for predicting the prognosis of ER-positive breast cancer patients receiving endocrine therapy.

A prognostic 10-lncRNA expression signature for predicting the risk of tumour recurrence in breast cancer patients.

Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death among females. Multiple molecular alterations are observed in breast cancer. LncRNA transcripts were proved to play important roles in the biology of tumorigenesis. In this study, we aimed to identify lncRNA expression signature that can predict breast cancer patient survival. We developed a 10-lncRNA signature-based risk score which was used to separate patients into high-risk and low-risk groups. Patients in the low-risk group had significantly better survival than those in the high-risk group. Receiver operating characteristic analysis indicated that this signature exhibited excellent diagnostic efficiency for 1-, 3- and 5-year disease-relapse events. Moreover, multivariate Cox regression analysis demonstrated that this 10-lncRNA signature was an independent risk factor when adjusting for several clinical signatures such as age, tumour size and lymph node status. The prognostic value of risk scores was validated in the validation set. In addition, a nomogram was established and the calibration plots analysis indicated the good performance and clinical utility of the nomogram. In conclusion, our results demonstrated that this 10-lncRNA signature effectively grouped patients at low and high risk of disease recurrence.

Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes.

BACKGROUND: The incidence of thyroid cancer in black Americans is significantly lower than that in white Americans, and the impact of race on the prognosis of thyroid cancer remains controversial. The purpose of this study was to determine the risk factors for survival in black and white patients and to compare the survival of differentiated thyroid carcinoma subtypes between these two races. We further investigated the association of lymph node and distant metastases with races. METHODS: This is a retrospective analysis using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A total of 70,346 cases were included in our study. Patients' demographics and cancer- and treatment-related characteristics were compared between the black and white Americans using chi-square and Fisher's exact tests. For multivariate analysis, Cox proportional hazards regression were used to assess the association between potential risk factors and the survival in black and white patients. RESULT: Black Americans had a worse overall survival than white Americans (HR = 1.127, P = 0.002). While disease-specific survival (DSS) was comparable, the risk factors for DSS were different between white and black Americans. Black Americans had less lymph node metastasis of classical variant papillary thyroid carcinoma (CPTC, OR = 0.476, P < 0.001) and follicular variant papillary thyroid carcinoma (FVPTC, OR = 0.522, P < 0.001), but not follicular thyroid carcinoma (FTC). However, black Americans with FVPTC, but not CPTC or FTC, had a higher potential of distant metastasis (OR = 1.715, P = 0.026). Furthermore, only white patients with tumor > 2 cm and lymph node metastasis benefited from radioactive iodine. CONCLUSIONS: The risk factors for DSS were significantly different in white and black patients. The impact of race should be considered in treatment strategy for thyroid cancer.

The Identification, Preservation and Classification of the External Branch of the Superior Laryngeal Nerve in Thyroidectomy.

BACKGROUND: Avoiding injury to the external branch of the superior laryngeal nerve is one of the major challenges during thyroid operation. The aim of this study was to propose a practical classification of the external branch of the superior laryngeal nerve. METHODS: A retrospective study of total thyroidectomy was performed. Totally 240 patients were included, with 480 external branches of the superior laryngeal nerves explored by intraoperative neuromonitoring. The classification of the external branch of the superior laryngeal nerve was determined by the distance between the upper edge of the superior thyroid pole and the lowest point of the nerve when the thyroid lobe was retracted in the lateral and inferior direction. Multinomial logistic regression analysis was run to predict the type of the nerve from several variables. RESULTS: The identification rate of the external branch of the superior laryngeal nerve was 98.54% (473 of 480 nerves). Higher ratio of longitudinal size of the thyroid lobe to ipsilateral neck length increased the likelihood of that both the type 2 and 3 nerve with respect to type 1 nerve, with OR 2.72, 95% CI = 1.21-6.12 and OR 5.30, 95% CI = 2.09-13.44, respectively. (1a) The nerve whose lowest point (entry into the muscle) was located more than 1 cm above the horizontal plane passing the upper border of superior thyroid pole. (1b) The nerve whose lowest point (the point right above the superior thyroid pole) was located more than 1 cm above the plane. (2a) The nerve whose lowest point (entry into the muscle) was located within 1 cm above the plane. (2b) The nerve whose lowest point (the point right above the superior thyroid pole) was located within 1 cm above the plane. (3a) The nerve whose lowest point (entry into the muscle) was located below the plane. (3b) The nerve whose lowest point (the point right below the superior thyroid pole) was located anterior to the gland. (3c) The nerve whose lowest point (the point right below the superior thyroid pole) was located posterior to the gland. CONCLUSIONS: Identification rate of the external branch of the superior laryngeal nerve by intraoperative neuromonitoring was significantly high. Understanding the new practical classification of the nerve allows for better identification and function preservation of this nerve during thyroidectomy.

Roles of lncRNAs related to the p53 network in breast cancer progression.

The p53 is a crucial tumor suppressor and transcription factor that participates in apoptosis and senescence. It can be activated upon DNA damage to regulate the expression of a series of genes. Previous studies have demonstrated that some specific lncRNAs are part of the TP53 regulatory network. To enhance our understanding of the relationship between lncRNAs and P53 in cancers, we review the localization, structure, and function of some lncRNAs that are related to the mechanisms of the p53 pathway or serve as p53 transcriptional targets.

Amyloid-ß neuropathology induces bone loss in male mice by suppressing bone formation and enhancing bone resorption.

Alzheimer's disease (AD) and osteoporosis often coexist in the elderly. Although observational studies suggest an association between these two diseases, the pathophysiologic link between AD and skeletal health has been poorly defined. We examined the skeletal phenotype of 5xFAD mice, an AD model with accelerated neuron-specific amyloid-ß accumulation causing full-blown AD phenotype by the age of 8 months. Micro-computed tomography indicated significantly lower trabecular and cortical bone parameters in 8-month-old male, but not female, 5xFAD mice than sex-matched wild-type littermates. Dynamic histomorphometry revealed reduced bone formation and increased bone resorption, and quantitative RT-PCR showed elevated skeletal RANKL gene expression in 5xFAD males. These mice also had diminished body fat percentage with unaltered lean mass, as determined by dual-energy X-ray absorptiometry (DXA), and elevated Ucp1 mRNA levels in brown adipose tissue, consistent with increased sympathetic tone, which may contribute to the osteopenia observed in 5xFAD males. Nevertheless, no significant changes could be detected between male 5xFAD and wild-type littermates regarding the serum and skeletal concentrations of norepinephrine. Thus, brain-specific amyloid-ß pathology is associated with osteopenia and appears to affect both bone formation and bone resorption. Our findings shed new light on the pathophysiologic link between Alzheimer's disease and osteoporosis.

Dendritic cell vaccines in breast cancer: Immune modulation and immunotherapy.

Breast cancer (BC) is the most common cancer in women worldwide. Although substantial progress has been made in the diagnosis and treatment of breast cancer, the efficacy and side effects of traditional treatment methods are still unsatisfactory. In recent years, immunotherapy including tumor vaccine has achieved great success in the treatment of BC. Dendritic cells (DCs) are multifunctional antigen-presenting cells that play an important role in the initiation and regulation of innate and adaptive immune responses. Numerous studies have shown that DC-based treatments might have a potential effect on BC. Among them, the clinical study of DC vaccine in BC has demonstrated considerable anti-tumor effect, and some DC vaccines have entered the stage of clinical trials. In this review, we summarize the immunomodulatory effects and related mechanisms of DC vaccine in breast cancer as well as the progress of clinical trials to propose possible challenges of DC vaccines and new development directions.

Integrin ß4 promotes DNA damage-related drug resistance in triple-negative breast cancer via TNFAIP2/IQGAP1/RAC1.

Anti-tumor drug resistance is a challenge for human triple-negative breast cancer (TNBC) treatment. Our previous work demonstrated that TNFAIP2 activates RAC1 to promote TNBC cell proliferation and migration. However, the mechanism by which TNFAIP2 activates RAC1 is unknown. In this study, we found that TNFAIP2 interacts with IQGAP1 and Integrin ß4. Integrin ß4 activates RAC1 through TNFAIP2 and IQGAP1 and confers DNA damage-related drug resistance in TNBC. These results indicate that the Integrin ß4/TNFAIP2/IQGAP1/RAC1 axis provides potential therapeutic targets to overcome DNA damage-related drug resistance in TNBC.

Lysine 2-Hydroxyisobutyrylation- and Succinylation-Based Pathways Act Inside Chloroplasts to Modulate Plant Photosynthesis and Immunity.

Crops must efficiently allocate their limited energy resources to survival, growth and reproduction, including balancing growth and defense. Thus, investigating the underlying molecular mechanism of crop under stress is crucial for breeding. Chloroplasts immunity is an important facet involving in plant resistance and growth, however, whether and how crop immunity modulated by chloroplast is influenced by epigenetic regulation remains unclear. Here, the cotton lysine 2-hydroxyisobutyrylation (Khib) and succinylation (Ksuc) modifications are firstly identified and characterized, and discover that the chloroplast proteins are hit most. Both modifications are strongly associated with plant resistance to Verticillium dahliae, reflected by Khib specifically modulating PR and salicylic acid (SA) signal pathway and the identified GhHDA15 and GhSRT1 negatively regulating Verticillium wilt (VW) resistance via removing Khib and Ksuc. Further investigation uncovers that photosystem repair protein GhPSB27 situates in the core hub of both Khib- and Ksuc-modified proteins network. The acylated GhPSB27 regulated by GhHDA15 and GhSRT1 can raise the D1 protein content, further enhancing plant biomass- and seed-yield and disease resistance via increasing photosynthesis and by-products of chloroplast-derived reactive oxygen species (cROS). Therefore, this study reveals a mechanism balancing high disease resistance and high yield through epigenetic regulation of chloroplast protein, providing a novel strategy to crop improvements.

Extra-Large Gα Protein (XLαs) Deficiency Causes Severe Adenine-Induced Renal Injury with Massive FGF23 Elevation.

Fibroblast growth factor-23 (FGF23) is critical for phosphate and vitamin D homeostasis. Cellular and molecular mechanisms underlying FGF23 production remain poorly defined. The extra-large Gα subunit (XLαs) is a variant of the stimulatory G protein alpha-subunit (Gsα), which mediates the stimulatory action of parathyroid hormone in skeletal FGF23 production. XLαs ablation causes diminished FGF23 levels in early postnatal mice. Herein we found that plasma FGF23 levels were comparable in adult XLαs knockout (XLKO) and wild-type littermates. Upon adenine-rich diet-induced renal injury, a model of chronic kidney disease, both mice showed increased levels of plasma FGF23. Unexpectedly, XLKO mice had markedly higher FGF23 levels than WT mice, with higher blood urea nitrogen and more severe tubulopathy. FGF23 mRNA levels increased substantially in bone and bone marrow in both genotypes; however, the levels in bone were markedly higher than in bone marrow. In XLKO mice, a positive linear correlation was observed between plasma FGF23 and bone, but not bone marrow, FGF23 mRNA levels, suggesting that bone, rather than bone marrow, is an important contributor to severely elevated FGF23 levels in this model. Upon folic acid injection, a model of acute kidney injury, XLKO and WT mice exhibited similar degrees of tubulopathy; however, plasma phosphate and FGF23 elevations were modestly blunted in XLKO males, but not in females, compared to WT counterparts. Our findings suggest that XLαs ablation does not substantially alter FGF23 production in adult mice but increases susceptibility to adenine-induced kidney injury, causing severe FGF23 elevations in plasma and bone.

TRIM11 promotes breast cancer cell proliferation by stabilizing estrogen receptor α.

Breast cancer is the most commonly diagnosed malignancy in female worldwide, over 70% of which are estrogen receptor α (ERα) positive. ERα has a crucial role in the initiation and progression of breast cancer and is an indicator of endocrine therapy, while endocrine resistance is an urgent problem in ER-positive breast cancer patients. In the present study, we identify a novel E3 ubiquitin ligase TRIM11 function to facilitate ERα signaling. TRIM11 is overexpressed in human breast cancer, and associates with poor prognosis. The protein level of TRIM11 is highly correlated with ERα. RNA-seq results suggest that ERα signaling may be an underlying target of TRIM11. Depletion of TRIM11 in breast cancer cells significantly decreases cell proliferation and migration. And the suppression effects can be reversed by overexpressing ERα. In addition, ERα protein level, ERα target genes expression and estrogen response element activity are also dramatically decreased by TRIM11 depletion. Further mechanistic analysis indicates that the RING domain of TRIM11 interacted with the N terminal of ERα in the cytoplasm and promotes its mono-ubiquitination, thus enhances ERα protein stability. Our study describes TRIM11 as a modulating factor of ERα and increases ERα stability via mono-ubiquitination. TRIM11 could be a promising therapeutic target for breast cancer treatment.

Co-transplantation with adipose-derived cells to improve parathyroid transplantation in a mice model.

BACKGROUND: Accidentally removed parathyroid glands are still challenging in neck surgery, leading to hypoparathyroidism characterized with abnormally low levels of parathyroid hormone. Parathyroid auto-transplantation is usually applied in compensation. To improve the efficiency of parathyroid transplantation, we introduced a method by co-transplanting with adipose-derived cells, including stromal vascular fractions (SVFs) and adipose-derived stem cells (ADSCs), and investigated the underlying molecular mechanisms involved in parathyroid transplantation survival. METHODS: Rat and human parathyroid tissues were transplanted into nude mice as parathyroid transplantation model to examine the effects of SVFs and ADSCs on grafts angiogenesis and survival rates, including blood vessel assembly and parathyroid hormone levels. Several angiogenic factors, such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF) 2, were assessed in parathyroid grafts. The effects of hypoxia were investigated on ADSCs. The modulatory roles of the eyes absent homolog 1 (EYA1), which is vital in parathyroid development, was also investigated on angiogenic factor production and secretion by ADSCs. All experimental data were statistically processed. Student's t test was used to assess significant differences between 2 groups. For multiple comparisons with additional interventions, two-way ANOVA followed by Tukey's post hoc test was performed. P < 0.05 was considered as significant. RESULTS: SVFs improve rat parathyroid transplantation survival and blood vessel assembly, as well as FGF2 and VEGF-A expression levels in parathyroid transplantation mice. Functional human parathyroid grafts have higher microvessel density and increased VEGF-A expression. The supernatant of ADSCs induced tubule formation and migration of human endothelial cells in vitro. Hypoxia had no effect on proliferation and apoptosis of human ADSCs but induced higher angiogenic factor levels of VEGF-A and FGF2, modulated by EYA1, which was confirmed by parathyroid glands transplantation in mice. CONCLUSIONS: Adipose-derived cells, including ADSCs and SVFs, improve parathyroid transplantation survival via promoting angiogenesis through EYA1-regulating angiogenetic factors in vitro and in vivo. Our studies proved an effective method to improve the parathyroid autotransplantation, which is promising for clinical patients with hypoparathyroidism when parathyroid glands were accidentally injured, removed, or devascularized.

Sapylin (OK-432) alters inflammation and angiogenesis in vivo and vitro.

BACKGROUND: The occurrence of seroma formation and long-term wound healing remain challenging complications after modified radical mastectomy. Sapylin is a drug used to reduce seroma formation and enhance wound closure, but these results remain controversial. We aimed to investigate the potential mechanism. METHODS: A prospective, consecutive cohort study included 120 patients diagnosed with breast cancer who underwent modified radical mastectomy was designed. Patients were randomized into two group, using or not using OK-432 (sixty patients per group) during surgeries. Patients' drainage fluids were collected for three days after surgery. Inflammatory cytokines and chemokines were measured with ELISA assays. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells HUVEC and HFL1 cells were measured after being treated with drainage fluids. RESULTS: Our clinic data showed that there was no statistical significance between the two groups in patient characteristics before surgery. However, the outcomes of patients in experimental group were significantly better than those in control group. In vitro studies, the results of ELISA assays showed that several cytokines, including IL-1a, IL-6, TGF-ß1, bFGF and VEGF were increased in the drainage fluids treated with Sapylin. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells were significantly enhanced after being treated with Sapylin group drainage fluids. CONCLUSION: Sapylin could stimulate the body to secrete a variety of cytokines to promote wound healing by promoting endothelial cell proliferation and migration, angiogenesis and by increasing fibroblast migration and collagen deposition.

Parathyroid autotransplantation at a novel site for better evaluation of the grafted gland function: study protocol for a prospective, randomized controlled trial.

BACKGROUND: Hypoparathyroidism is one of the most common complications encountered in thyroidectomy. In addition to parathyroid in-situ preservation, parathyroid autotransplantation (PA) is another important remedial method for patients whose parathyroid glands have been removed. However, an accurate evaluation method for the function of a transplanted parathyroid is lacking. Our preliminary study indicated that patients with PA at novel sites near antecubital veins had higher serum concentrations of parathyroid hormone (PTH). Therefore, the main hypothesis is that a grafted site closer to the cephalic vein is more useful for better evaluation of transplanted parathyroid function. This study aims to confirm the more efficient and accurate evaluation system through a prospective, randomized controlled trial. METHODS: In total, 280 patients will be enrolled in this study and randomly divided into two groups: 140 patients with transplanted parathyroid glands in the traditional sites (group A) and the other 140 transplanted in the novel sites (group B), close to the antecubital veins. The serum concentration of PTH and calcium ion from both forearms will be measured and monitored regularly for 12 months. The primary outcome of this trial will be the survival of grafted glands, defined as the ratio of PTH between the grafted vs. the non-grafted forearms being no less than 1.5. The secondary outcome is hypoparathyroidism, defined as the PTH level from the non-grafted forearms being less than 15 pg/ml (normal range 15-65 pg/ml). DISCUSSION: Our results from this study should provide a more accurate method to evaluate the function of transplanted parathyroid glands by comparing PTH concentrations in both the grafted and non-grafted forearms following PA at novel sites. A better PTH measurement is helpful not only for the management of postoperative patients, but also for further identification of factors affecting PA success. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02906748 . Registered on 16 March 2016.