[Three-dimensional radiographic features of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor].

OBJECTIVE: To analyze the three-dimensional radiographic characteristics of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor using spiral computed tomography (CT) and cone-beam computed tomography (CBCT). METHODS: Clinical records, histopathological reports, and CBCT or non-enhanced spiral CT images of 19 consecutive patients with calcifying odontogenic cyst (COC) and 16 consecutive patients with calcifying epithelial odontogenic tumor (CEOT) were retrospectively acquired, and radiographic features, including location, size, expansion, internal structure and calcification, were analyzed. RESULTS: Among the 19 COC cases (12 males and 7 females, with an average age of 27 years), 89.5% (17/19) of the lesions originated from the anterior and premolar areas, 100.0% of them exhibited cortex expansion, and 78.9% had discontinued cortex. Among the 16 CEOT cases (3 males and 13 females, with an average age of 36 years), 81.3% (13/16) of the lesions were in the premolar and molar areas, 56.3% of them exhibited cortex expansion, and 96.8% had discontinued cortex. According to the distribution of internal calcifications, these lesions were divided into: Ⅰ (non-calcification type): absence of calcification; Ⅱ (eccentric marginal type): multiple calcifications scattered along one side of the lesion; Ⅲ (diffused type): numerous calcifications diffusely distributed into the lesion; Ⅳ (plaque type): with a ≥ 5 mm calcified patch; Ⅴ (peri-coronal type): multiple calcifications clustered around impacted teeth. Calcifications were present in 73.7% of COC lesions, including 9 type Ⅱ, 3 type Ⅲ and 2 type Ⅳ lesions, and 42.8% of CEOT lesions had calcification images, including 2 type Ⅲ and 5 type Ⅴ lesions. Six COC lesions had odontoma-like images. Moreover, 8 of 9 type Ⅰ CEOTs were histologically Langerhans cell-rich subtype, which had a smaller size (with an average mesiodistal diameter of 17.8 mm) and were not associated with impacted teeth. CONCLUSION: COC lesions tended to originate from the anterior part of the jaw and exhibit cortex expansion, and were sometimes associated with odontoma. CEOT commonly occurred in the posterior jaw and had discontinued cortex. Two lesions had significantly different calcification map. Over 70% of COC lesions had calcification images, which were mostly scattered along one side of the cysts, far from the impacted teeth. Approximately 60% of CEOT lesions exhibited smaller size and non-calcification, and the remaining CEOT cases often had calcification images clustered around the impacted teeth.

High-Performance Transparent Ultrabroadband Electromagnetic Radiation Shielding from Microwave toward Terahertz.

In the era of fifth-generation networks and Internet-of-Things, the use of multiband electromagnetic radiation shielding is highly desirable for next-generation electronic devices. Herein, we report a systematic exploration of optoelectronic behaviors of ultrathin-silver-based shielding prototype (USP) film structures at the nanometer scale, unlocking the transparent ultrabroadband electromagnetic interference (EMI) shielding from microwave to terahertz frequencies. A theoretical model is proposed to optimize USP structures to achieve increased transparency, whereby optical antireflection resonances are introduced in dielectrics in conjunction with remarkable EMI shielding capability. USP can realize a state-of-the-art effective electromagnetic radiation shielding bandwidth with measured frequencies from 8 GHz up to 2 THz. Experimental results show that a basic USP (dAg = 10 nm) offers an average shielding efficiency of ∼27.5 dB from the X- to Ka-bands (8-40 GHz) and maintains a stable shielding performance of ∼22.6 dB across a broad range of 0.5-2 THz, with a measured optical transmittance of ∼95.2%. This extraordinary performance of ultrathin-silver-based film structures provides a new ultrabroadband EMI shielding paradigm for potential applications in next-generation electronics.

Confirmation of eosinophilic sialodochitis by terminal duct biopsy.

OBJECTIVE: To analyse the histopathological features of eosinophilic sialodochitis by using terminal duct biopsy. METHODS: Sixty-five patients with suspected eosinophilic sialodochitis and four with chronic obstructive sialadenitis were prospectively enrolled. Clinical features, laboratory tests and sialograms were comparatively analysed. Terminal duct biopsy of the parotid or submandibular glands was performed concomitantly with endoscopy-assisted duct dilatation to determine the histopathological features of eosinophilic sialodochitis. RESULTS: Based on eosinophil quantification, the samples of suspected patients were scored as 'definite', 'highly suspected' and 'negative' in 26 (40%), 15 (23.1%) and 24 (36.9%) cases, respectively. Gland types and peripheral blood eosinophil counts were significantly different among these three groups. The proportions of itching glands, mucus plug exudations and elevated immunoglobulin E levels were higher in the 'definite' group than in the other two groups; however, the intergroup differences were insignificant. The primary pathological features of eosinophilic sialodochitis were abundant eosinophils and lymphocytes infiltrated around the duct, degranulation of eosinophils, extensive fibrosis and scattered mastocytes. Periductal eosinophils were not found in cases of chronic obstructive sialadenitis. CONCLUSION: Our findings suggest that terminal duct biopsy is safe and valuable for the pathological confirmation of eosinophilic sialodochitis, and can be used simultaneously with endoscopy-assisted duct dilatation.

S100A6 promotes the development of thyroid cancer and inhibits apoptosis of thyroid cancer cells through the PI3K/AKT/mTOR pathway.

High levels of S100A6 have been associated with progression in some types of human cancers. Cancers related to S100A6 have been reported to include lung cancer, cervical cancer, pancreatic cancer, gastric cancer, colon cancer, etc., but its role in the molecular pathogenesis of these cancers is largely unknown. This study investigated the expression and functional roles of S100A6 in human thyroid cancer. The expression level of S100A6 in thyroid cancer cells was determined by bioinformatics and transcriptomic analysis. Furthermore, the potential functions of S100A6 in tumorigenesis were analyzed by cell proliferation, migration, invasion, and Western blot assays in human thyroid cancer cells. Public database queries revealed high S100A6 expression in thyroid cancer. In addition, we also found that high expression of S100A6 was positively correlated with malignant clinicopathological characteristics of thyroid cancer in The Cancer Genome Atlas database. qPCR results confirmed the high expression of S100A6 in thyroid cancer cells. S100A6 silencing inhibited cell proliferation, migration, and invasion. Western blot assays and response experiments showed that S100A6 promotes cell proliferation and tumorigenicity partly through the PI3K/AKT/mTOR signaling pathway. These results suggest that S100A6 affects the progression of thyroid cancer and can be used as a target in the future treatment of thyroid cancer.

Fibrinogen-to-Neutrophil Ratio as a New Predictor of Central Lymph Node Metastasis in Patients with Papillary Thyroid Cancer and Type 2 Diabetes Mellitus.

Background: Many patients have a higher risk of thyroid cancer if they have both papillary thyroid carcinoma (PTC) and Type 2 diabetes mellitus (T2DM). Meanwhile, the primary reason for local PTC recurrence is cervical lymph node metastasis. Therefore, the prognosis of patients affects how cervical lymph nodes are managed during surgery. Due to surgical complications such as laryngeal nerve palsy and hypocalcemia, it is still debatable whether to prevent central lymph node dissection (CLND). Predicting central lymph node metastasis (CLNM) is crucial to direct CLND. It is unclear how important the fibrinogen-to-neutrophil ratio (FNR) is in thyroid cancer, so we looked into how it might help patients with PTC and T2DM predict CLNM. Patients and methods: Wenzhou Medical University's First Affiliated Hospital provided us with 413 patients with PTC and T2DM, randomly divided into a training set (N = 292) and a validation set (N = 121). Univariate and multivariate logistic regression analyses were used to identify independent risk factors. After constructing a nomogram, the validity of the model was evaluated. Results: The maximum tumor diameter, high-density lipoprotein, thyroxine, triglyceride, lymphocyte, and FNR were all identified as independent risk factors by multivariate logistic regression analysis. The C index of the training set was 0.775, and the validation set was 0.654. Conclusion: In patients with PTC and T2DM, preoperative FNR was an independent risk factor for CLNM.

PDZK1IP1 gene promotes proliferation, migration, and invasion in papillary thyroid carcinoma.

Thyroid cancer is a common malignant tumor for the adult and the potential molecular mechanism of papillary thyroid cancer cell metastasis is still unclear. We used sequencing techniques to analyze paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissue and identified a gene, PDZK1IP1, that was significantly overexpressed in thyroid cancer. We found It has been detected to play an important role in many malignant tumors. But the role in papillary thyroid cancer was still unknown, we decided to find a new marker and therapeutic target for the disease. The present study shows that PDZK1IP1 may be a potential gene that leads to thyroid cancer. In our study, silencing PDZK1IP1 can inhibit PTC cell proliferation, migration, invasion, apoptosis, and cell cycle arrest. This study surmised that PDZK1IP1 was an oncogene that correlated with tumor development.

Age-specific random day serum antimüllerian hormone reference values for women of reproductive age in the general population: a large Chinese nationwide population-based survey.

BACKGROUND: Antimüllerian hormone, the most reliable biomarker of ovarian reserve, is widely used in various clinical situations. Antimüllerian hormone levels consistently decrease with age. However, there is no standard, age-specific reference values for antimüllerian hormone in women of reproductive age, which limits its application. OBJECTIVE: This study aimed to establish age-specific antimüllerian hormone percentile reference values for women of reproductive age. STUDY DESIGN: A nationwide, population-based cross-sectional survey was conducted between May 2019 and April 2021 in 15 provinces and municipalities in mainland China. A total of 10,053 eligible women aged 20 to 49 years were selected using a multistage stratified sampling procedure. Women who were pregnant, had undergone ovarian surgery, took hormone drugs in the past 3 months, or had an antimüllerian hormone outlier value were excluded from establishing antimüllerian hormone percentile reference values. Serum antimüllerian hormone concentrations were measured using ultrasensitive, 2-site enzyme-linked immunosorbent assays (Ansh Lab, Webster, TX) in the Reproductive Endocrinology Laboratory of Peking University Third Hospital. Generalized additive models for location scale and shape with the Box-Cox t original distribution were used to estimate the fitted antimüllerian hormone percentile reference values. RESULTS: A total of 9112 eligible women aged 21 to 49 years were included in the fitting model. The fitted 50th (2.5th-97.5th) percentiles of antimüllerian hormone values for women aged 21, 25, 30, 35, 40, 45, and 49 years were 4.83 (0.79-18.41), 4.47 (0.72-16.58), 3.67 (0.50-13.82), 2.59 (0.24-10.35), 1.35 (0.05-6.68), 0.33 (<0.01 to 3.40), and 0.04 (<0.01 to 1.77) ng/mL, respectively. The population-based decline rate of antimüllerian hormone accelerated with increasing age, especially age >35 years. The magnitude of the decline of the 25th antimüllerian hormone percentile curve was greater than that of the 75th percentile curve. CONCLUSION: This study established age-specific antimüllerian hormone percentile reference values for women of reproductive age based on a large representative sample of the general population and described antimüllerian hormone changes. These findings may facilitate antimüllerian hormone application in clinical practices.

Downstream Neighbor of Son Overexpression is Associated With Breast Cancer Progression and a Poor Prognosis.

PURPOSE: The incidence rate of breast cancer (BC) has increased annually. Downstream neighbor of son (DONSON) critically affects cell cycle progression and maintains stable genomic properties; however, its relevant effects on BC growth and progression require in-depth investigation. METHODS: DONSON upregulation was validated in public databases. DONSON expression in matched BC and adjacent tissues and cell lines (MDA-MB-231, BT-549, and HS-578T) was determined using quantitative reverse transcription polymerase chain reaction. In vitro apoptosis, invasion, migration, and proliferation tests were performed to ascertain the functions of DONSON in BC cell lines. Then, using western blot analysis, the levels of DONSON downstream proteins were determined. RESULTS: Compared to the control, DONSON was expressed at higher levels in BC tissues and cell lines. DONSON knockdown facilitated apoptosis and limited proliferation, migration, invasion, and S/G2 transition of BC cells in vitro. Furthermore, DONSON overexpression promoted BC cell proliferation and inhibited apoptosis in vitro. Moreover, DONSON knockdown reduced cyclin A1 and cyclin-dependent kinase 2 levels. Moreover, DONSON knockdown limited the progression of epithelial-mesenchymal transition. CONCLUSION: DONSON critically affects BC growth and serves as a possible target and marker for the efficacy of subsequent therapies.

A Novel and Effective Model to Predict Skip Metastasis in Papillary Thyroid Carcinoma Based on a Support Vector Machine.

Introduction: Skip metastasis, referred to as lymph node metastases to the lateral neck compartment without involvement of the central compartment, is generally unpredictable in papillary thyroid carcinoma (PTC). This study aims to establish an effective predictive model for skip metastasis in PTC. Meterials and Methods: Retrospective analysis was performed of clinical samples from 18192 patients diagnosed with thyroid cancer between 2016 to 2020. The First Affiliated Hospital of Wenzhou Medical University. The lateral lymph node metastasis was occureed in the training set (630 PTC patients) and validation set (189 PTC patients). The univariate and multivariate analyses were performed to detect the predictors of skip metastasis and the support vector machine (SVM) was used to establish a model to predict skip metastasis. Results: The rate of skip metastasis was 13.3% (84/631). Tumor size (≤10 mm), upper location, Hashimoto's thyroiditis, extrathyroidal extension, absence of BRAFV600E mutation, and less number of central lymph node dissection were considered as independent predictors of skip metastasis in PTC. For the training set, these predictors performed with 91.7% accuracy, 86.4% sensitivity, 92.2% specificity, 45.2% positive predictive value (PPV), and 98.9% negative predictive value (NPV) in the model. Meanwhile, these predictors showed 91.5% accuracy,71.4% sensitivity, 93.1% specificity, 45.5% PPV, and 97.6% NPV in validation set. Conclusion: This study screened the predictors of the skip lateral lymph node metastasis and to establish an effective and economic predictive model for skip metastasis in PTC. The model can accurately distinguish the skip metastasis in PTC using a simple and affordable method, which may have potential for daily clinical application in the future.

Glucose-to-Lymphocyte Ratio (GLR) as a Predictor of Preoperative Central Lymph Node Metastasis in Papillary Thyroid Cancer Patients With Type 2 Diabetes Mellitus and Construction of the Nomogram.

Background: Detection of metastasis of central lymph nodes in papillary thyroid cancer is difficult before surgery. The role of routine or preventive central lymph node dissection in the management of papillary thyroid cancer remains inconclusive. Moreover, glucose metabolism and systemic inflammation are related to the aggressiveness of several malignant tumors and the prognoses of these patients. This study aimed to construct a nomogram based on the readily available preoperative clinical features for predicting the occurrence of preoperative central lymph node metastasis in patients with papillary thyroid cancer and type 2 diabetes mellitus. The findings may underlie clinical implications for determining the appropriate treatment strategies for these patients. Methods: A total of 419 patients were enrolled. We used the receiver operating characteristic curves to determine the best cut-off value and converted the continuous into categorical variables. Next, a single-factor logistic analysis for the independent variables was performed, following which a multivariate regression analysis was conducted for the selected significant risk factors. Finally, the nomogram was constructed and verified using external data; the existing data were compared with the original model. Results: According to the receiver operating characteristic curves, the best cut-off values ​​for glucose-to-lymphocyte ratio and tumor size were 4.23 cm and 0.95 cm, respectively. Findings from the multivariate logistic regression analysis suggested that age, bilateral tumors, maximum tumor size, and the ratio of glucose-to-lymphocytes were independent risk factors for preoperative central lymph node metastasis. The C-indexes in the training and the external validation data sets were 0.733 and 0.664, respectively. Both calibration curves and the Hosmer-Lemeshow tests indicated that the model was well-calibrated. Through decision curve analysis, the predictive model was estimated to have strong clinical applicability and greater benefits. To compare the performance of the new with that of the original model, we performed a net reclassification index and the integrated discrimination improvement analyses, both of which indicated that the new model had a better predictive ability. Conclusion: In patients with type 2 diabetes mellitus and papillary thyroid cancer, a high preoperative glucose-to-lymphocyte ratio was an independent predictor of the preoperative central lymph node metastasis. The nomogram so constructed could better predict the preoperative central lymph node metastasis in these patients.

The Overexpression and Clinical Significance of AP1S1 in Breast Cancer.

Purpose: To explore the mechanism of AP1S1 in breast cancer. Methods and Results: In different datasets, we found that AP1S1 is more highly expressed in breast tumors, which was furthermore verified in our local cohort.Immune infiltration analysis showed that AP1S1 was related to a variety of immune cells. The higher AP1S1 expression was negatively correlated with a variety of immune infiltrating cells, suggesting that AP1S1 may affect cellular immunity.Clinical analysis showed that patients with higher AP1S1 expression had higher estrogen receptor gene expression and were more prone to distant metastasis and lymph node metastasis.The overall survival rate, disease-specific survival rate, and progression-free interval time were worse in the group with higher AP1S1 expression. AP1S1 may be a potential oncogene of breast cancer, and overexpression is related to the poor prognosis of breast cancer.Therefore, a nomogram was constructed, along with correlated gene analysis and functional analysis to further explore the carcinogenic mechanism, practical clinical issues, and value of AP1S1. Conclusion: AP1S1 is a potential oncogene of breast cancer.

The ETNK2 gene promotes progression of papillary thyroid carcinoma through the HIPPO pathway.

Thyroid cancer is a disease with an extremely high incidence rate and is divided into papillary, follicular, medullary, and undifferentiated thyroid cancers. Among them, papillary carcinoma is the most common subtype. We assessed expression of ETNK2 in public databases and found that ETNK2 is upregulated in PTC. Cohort and RNA sequencing data were used to verify this discovery. To further determine the relationship between ETNK2 and papillary thyroid carcinoma, we performed an in vitro experiment. In a PTC cell line, silencing ETNK2 inhibited cell proliferation, weakened cell migration and invasion ability, promoted apoptosis, and blocked the cell cycle. In addition, western blotting suggested that ETNK2 is related to the HIPPO pathway and may activate the EMT pathway through the HIPPO pathway to promote the development of thyroid cancer. These results revealed that ETNK2 is related to the occurrence and development of papillary thyroid carcinoma, suggesting that ETNK2 may be an oncogene associated with PTC.

In vitro maturation without gonadotropins versus in vitro fertilization with hyperstimulation in women with polycystic ovary syndrome: a non-inferiority randomized controlled trial.

STUDY QUESTION: Does in vitro maturation (IVM) result in non-inferior cumulative live birth rates compared to those after standard in vitro fertilization (IVF) in infertile women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: One cycle of IVM, without any stimulation, was inferior to one cycle of standard IVF in women with PCOS in terms of 6-month cumulative live birth rates, when choosing single vitrified-warmed blastocyst transfer. WHAT IS KNOWN ALREADY: IVM is an emerging alternative treatment for women with PCOS who need assisted reproductive technology. Since a minimal or even zero dose of gonadotropins are required in the IVM procedure, the occurrence of ovarian hyperstimulation syndrome (OHSS) is eliminated. Only one clinical trial comparing the pregnancy outcome between IVM with FSH priming and IVF has been reported. However, it is still unknown whether IVM treatment without any stimulation can offer a similar live birth outcome in women with PCOS as compared to that in women receiving the standard IVF procedure with ovarian stimulation. STUDY DESIGN, SIZE, DURATION: This single-centre, open-label randomized controlled non-inferiority trial in an academic infertility centre in China was performed between March 2018 and July 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 20-38 years with PCOS and infertility scheduled for their first IVF attempt were eligible. In total, 351 women were randomly allocated to receive one cycle of unstimulated IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol and hCG as ovulatory trigger (n = 176). A freeze-all and single blastocyst transfer strategy was used in both groups. The primary outcome was ongoing pregnancy (leading to live birth) within 6 months after randomization. A non-inferiority margin of 15% was considered. MAIN RESULTS AND THE ROLE OF CHANCE: The IVM procedure without additional gonadotropin resulted in a lower ongoing pregnancy (leading to live birth) within 6 months after randomization compared to standard IVF treatment (22.3% vs. 50.6%; rate difference -28.3%; 95% confidence interval [CI]: -37.9% to -18.7%). Moderate-severe OHSS did not occur in the IVM group, while in the IVF group, ten women (5.7%) had moderate OHSS and one woman (0.6%) had severe OHSS. There was no statistically significant difference in the occurrence of obstetric and perinatal complications. LIMITATIONS, REASONS FOR CAUTION: The trial was conducted using an IVM protocol without additional stimulation in a single centre, which may limit its generalizability. In addition, a GnRH agonist trigger rather than hCG for IVF stimulation in women with PCOS would be more consistent with current clinical practice. WIDER IMPLICATIONS OF THE FINDINGS: Although IVM is considered to be a convenient, inexpensive and safe alternative to IVF for women with PCOS, our results indicated that one cycle of IVM without any stimulation was inferior to one cycle of standard IVF in terms of the cumulative live birth rate. The inferiority of IVM without ovarian stimulation could be mainly due to the limitations in the developmental potential of embryos. Further IVM development should be tested and validated in a freeze-only and blastocyst transfer setting. Further RCTs are needed to evaluate the effectiveness and safety of other IVM protocols or multiple cycles of IVM compared to IVF. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2016YFC1000201 and 2018YFC1002104) and the National Science Foundation of China (81730038). B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). All other authors declare no competing interests. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03463772. TRIAL REGISTRATION DATE: 29 January 2018. DATE OF FIRST PATIENT'S ENROLMENT: 16 March 2018.

SYT12 is a novel oncogene that promotes thyroid carcinoma progression and metastasis.

Background: Thyroid malignancy is the most frequent endocrine malignant tumor whose incidence is still increasing. Mechanisms genomic variations play a major part in the pathogenesis of many types of malignancy. Synaptotagmin 12 (SYT12) is a member gene of the synaptotagmins family and SYT12's variants were shown to be associated with some malignancies. Nevertheless, SYT12's specific function and probable clinical value in papillary cancer were still unknown. Methods: We conducted complete genome sequence of 39 pairs PTC malignant neoplasm and matched non-neoplastic tissues. We found that SYT12 was significantly overexpressed in thyroid malignancy. Next, we investigated the expression level of SYT12 and the relation between clinical information and SYT12 expression in thyroid cancer in the Cancer Genome Atlas (TCGA). QRt-PCR of else 40 pairs local verified cohort was performed to confirm the sequencing data and TCGA cohort. Then, we used small interfering RNA (si-RNA) to knock down the expression of SYT12 in PTC cells. Finally, proliferation, cell colony formation, migration, invasion, and apoptosis assays were done to demonstrate the function of SYT12. Results: SYT12 is significantly overexpressed and higher expression of SYT12 upsurges the risk of lymph node metastatic and incidence rate of primary neoplasm multivariate focus type and classical histological type for PTC patients in TCGA cohort. In vitro experiments, the results of functional assays presented that knock-down of SYT12 inhibited the cell proliferation, cell colony formation, trans-well migration, and trans-well invasion and promoted cell apoptotic in PTC cell lines. Conclusion: SYT12 was a novel oncogene that promotes thyroid carcinoma progression and metastasis potential and a potential biomarker for diagnosis and treatment in PTC.

PSD3 is an oncogene that promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in papillary thyroid cancer.

Background: The morbidity of thyroid cancer is gradually increasing, meanwhile, the average age of the morbidity population also becomes younger. Mechanisms genomic variations serve an important function for the pathogenesis of many cancer types. Pleckstrin and sec7 domain-containing 3 (PSD3), also known as EFA6R, was shown to be associated with some cancers such as acute myeloid leukemia, breast cancer metastasis, and astrocytoma. But it was unknown that whether PSD3 took effect and how did it work in thyroid cancer. Methods: We guessed that PSD3 might play an important role in thyroid cancer by consulting previous literature. Then, we analyzed the level of PSD3 expression in thyroid malignancy and the connection with clinical manifestation in The Cancer Genome Atlas (TCGA). And RNA extraction, reverse transcription, and real-time quantitative polymerase chain reaction (qRt-PCR) of 40 pairs of local samples were done to verify the result of TCGA. Then, PSD3 was knocked down by small interfering RNA (siRNA) for flowing functional experiments. Results: Bioinformatics and qRt-PCR analysis shown PSD3 was overexpressed in papillary thyroid cancer (PTC) and connected with the histological type (P=0.009) and risk of lymph node metastasis (P=0.016). In vitro assays, we confirmed that down-regulation PSD3 could not only suppress the cell proliferation, colony formation, cell migration, cell invasion, and G1/S cell cycle transition but also promote apoptosis in PTC cells. Conclusion: PSD3 promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in PTC and a possible biomarker in PTC.

Nanobody Conjugates for Targeted Cancer Therapy and Imaging.

Conventional antibody-based targeted cancer therapy is one of the most promising avenues of successful cancer treatment, with the potential to reduce toxic side effects to healthy cells surrounding tumor cells. However, the full potential of antibodies is severely limited due to their large size, low stability, slow clearance, and high immunogenicity. Alternatively, recently discovered nanobodies, which are the smallest naturally occurring antigen-binding format, have shown great potential for addressing these limitations. Bioconjugation of nanobodies to functional groups such as toxins, enzymes, radionucleotides, and fluorophores can improve the efficacy and potency of nanobodies, enhance their in vivo pharmacokinetics, and expand the range of potential applications. Herein, we review the superior characteristics of nanobodies in comparison to conventional antibodies and provide insight into recent developments in nanobody conjugates for targeted cancer therapy and imaging.

LEM domain containing 1 promotes thyroid cancer cell proliferation and migration by activating the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition.

Thyroid cancer (TC) is the most common type of endocrine malignancy in humans, and its relative incidence has increased continuously in recent years. However, the primary molecular mechanisms of thyroid tumorigenesis and progression remain unclear. Papillary TC (PTC) is the most common subtype of TC. Recent studies have reported that one of the tumorigenesis and progression mechanisms is driven by genetic alterations that regulate the TC cell signaling pathway. In the present study, RNA sequencing (RNA-seq) was performed on 79 paired PTC and adjacent normal thyroid tissues to further study the molecular mechanisms of TC. Reverse transcription-quantitative PCR was used to detect the expression levels of LEM domain containing 1 (LEMD1) in 47 paired PTC and adjacent normal thyroid tissue samples. Initial analysis revealed that LEMD1 expression was significantly upregulated in TC tissues compared with that in normal tissues. The results of the thyroid RNA-seq datasets from The Cancer Genome Atlas were consistent with the RNA-seq analysis results of the present study. High LEMD1 expression increased the risk of lymph node metastasis in patients with TC. The biological function of LEMD1 on cell proliferation, migration, invasion and apoptosis was investigated in vitro via small interfering RNA and overexpression vector. Gene set enrichment analysis indicated that high LEMD1 expression was associated with epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin signaling pathway. Western blotting revealed that LEMD1 modulated the protein expression levels of E-cadherin, N-cadherin, vimentin, ß-catenin and cleaved-caspase 3. In conclusion, the present results indicated that LEMD1 may drive TC cell tumorigenesis and progression by activating the Wnt/ß-catenin signaling pathway and EMT.

Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway.

In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.

Immortalization up-regulated protein promotes tumorigenesis and inhibits apoptosis of papillary thyroid cancer.

The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up-regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf-like PTC patients with higher IMUP expression had shorter disease-free survival. The biological function of IMUP in PTC cell lines (KTC-1 and TPC-1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis-related molecules were identified by real-time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down-regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.

Prevalence of oligomenorrhea among women of childbearing age in China: A large community-based study.

OBJECTIVE: To investigate the prevalence and the related characteristics of oligomenorrhea among women within childbearing age in China. STUDY DESIGN: A large-scale community-based investigation was conducted from 2013 to 2015. A total of 12,964 women aged 18-49 years from 9 provinces/municipalities in China were recruited for healthcare screening in local community health centers. Outcome measures include clinical history, ultrasonographic exam, and hormonal and metabolic parameters. RESULTS: Among women within childbearing age in China, the prevalence of oligomenorrhea was 12.2% (1,579/12,964). Both sociodemographic factors and medical history were significantly associated with oligomenorrhea (P < 0.05). In such women, the prevalence of obesity, acne, seborrhea, acanthosis, larger ovarian size, and polycystic ovarian morphology was higher when compared with normal women; the prevalence of anti-Mullerian hormone, total testosterone, and androstenedione (P < 0.05) was higher as well. The infertility rates of all women were higher in the oligomenorrhea group (17.2%, 272/1,579) than in the non-oligomenorrhea group (9.0%, 1,024/11,385), and among women without contraception, for the oligomenorrhea group, the infertility rate was 32.5% (128/394), and for the non-oligomenorrhea group, 17.9% (400/2,240). In the oligomenorrhea group, 57.4% (156/272) of the women underwent treatments for infertility, which was higher than the non-oligomenorrhea group 36.1% (370/1,024). CONCLUSIONS: Obesity, acne, seborrhea, acanthosis, larger ovarian size, and polycystic ovarian morphology were significantly associated with oligomenorrhea. The increase of anti-Mullerian hormone, total testosterone, and androstenedione level was also demonstrated in the oligomenorrhea group. Higher prevalence of infertility and medical treatment rate was observed in women with oligomenorrhea.