Neuroendocrine carcinoma of the endometrium: a retrospective analysis of data from a single center.

BACKGROUND: Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. METHODS: We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. RESULTS: The median age of the patients was 55.0 (39.0-64.0) years, and the median tumor size was 40.0 (33.0-60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3-81.0) months. Unfortunately, 2 patients died from the disease. CONCLUSION: NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery.

Quantitative proteomics analysis in small cell carcinoma of cervix reveals novel therapeutic targets.

BACKGROUND: As a rare pathologic subtype, small cell carcinoma of the cervix (SCCC) is characterized by extensive aggressiveness and resistance to current therapies. To date, our knowledge of SCCC origin and progression is limited and sometimes even controversial. Herein, we explored the whole-protein expression profiles in a panel of SCCC cases, aiming to provide more evidence for the precise diagnosis and targeting therapy. METHODS: Eighteen SCCC samples and six matched normal cervix tissues were collected from January 2013 to December 2017. Data independent acquisition mass spectrometry (DIA) was performed to discriminate the different proteins (DEPs) associated with SCCC. The expression of CDN2A and SYP in corresponding SCCC tissues was verified using immunohistochemistry. GO and KEGG enrichment analyses were used to identify the key DEPs related to SCCC development and tumor recurrence. RESULTS: As a result, 1311 DEPs were identified in SCCC tissues (780 up-regulated and 531 down-regulated). In up-regulated DEPs, both GO analysis and KEGG analysis showed the most enriched were related to DNA replication (including nuclear DNA replication, DNA-dependent DNA replication, and cell cycle DNA replication), indicating the prosperous proliferation in SCCC. As for the down-regulated DEPs, GO analysis showed that the most enriched functions were associated with extracellular matrix collagen-containing extracellular matrix. KEGG analysis revealed that the DEPs were enriched in Complement and coagulation cascades, proteoglycans in cancer, and focal adhesion-related pathways. Down-regulation of these proteins could enhance the mobility of cancer cells and establish a favorable microenvironment for tumor metastasis, which might be accounted for the frequent local and distant metastasis in SCCC. Surprisingly, the blood vessels and circulatory system exhibit a down-regulation in SCCC, which might be partly responsible for its resistance to anti-angiogenic regimens. In the stratification analysis of early-stage tumors, a group of enzymes involved in the cancer metabolism was discriminated in these recurrence cases. CONCLUSIONS: Using quantitative proteomics analysis, we first reported the whole-protein expression profiles in SCCC. Significant alterations were found in proteins associated with the enhancement of DNA replication and cellular motility. Besides the association with mitosis, a unique metabolic feature was detected in cases with tumor recurrence. These findings provided novel targets for disease surveillance and treatments, which warranted further validation in the future.

Real-world Efficacy Data on Anti-Angiogenic Drugs in Recurrent Small Cell Cervical Carcinoma: A Retrospective Study.

OBJECTIVE: Small cell carcinoma of the cervix (SCCC) is rare but extremely aggressive and resistant to current therapies. We herein evaluate the efficacy of bevacizumab, apatinib, and anlotinib in recurrent/metastatic SCCC patients in a real-world setting. METHODS: Recurrent/metastatic SCCC patients were recruited between January 2013 and July 2020. Baseline characteristics were extracted from medical records, and patients were divided into an anti-angiogenic group and non-anti-angiogenic group. The efficacy of treatments was determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Kaplan-Meier analysis was performed for survival analysis. RESULTS: Sixteen patients received anti-angiogenic drugs after tumor recurrence/metastasis; of them, 10 cases received them as first-line treatment, 5 cases as second-line treatment, and 1 case as fourth-line treatment. Another 23 patients received traditional therapies, including surgery, chemotherapy, and radiotherapy. The use of anti-angiogenic drugs in first-line treatment significantly prolonged progression-free survival (PFS) compared to the controls, with a median PFS of 8 months (2-20 months) and 3 months (1-10 months), respectively (P = .025). This trend was also notable in patients who started anti-angiogenic treatment after the second-line recurrence/metastasis. However, there was no benefits for overall survival (OS) in either the 10 first-line cases or all 16 cases (P = .499 and .31, respectively). Both bevacizumab and small molecule drugs (apatinib and anlotinib) presented similar efficacy in SCCC patients. CONCLUSIONS: At present, this is the largest cohort study that provides real-world data, showing that anti-angiogenic regimens could significantly prolong PFS in recurrent/metastatic SCCC. Aside from bevacizumab, the novel oral small molecule drugs provide more choices with similar efficacy. These findings warrant further validation in well-designed future studies.

Separation of a new triterpenoid saponin together with six known ones from Clematis tangutica (Maxim.) Korsh and evaluation of their cytotoxic activities.

A new triterpenoid saponin, 3-O-ß-D-allopyranosyl (1→3)-α-L-rhamnopyranosyl (1→2)-α-L-arabinopyranosyl hederagenin 28-O-α-L-rhamnopyranosyl (1→4)-ß-D-glucopyranosyl (1→6)-ß-D-glucopyranosyl ester (IV), together with six known ones Hederacholichiside F (I), Tanguticoside B (II), Tauroside St-H1 (III), Hederoside H1 (V), Kalopanaxsaponin G (VI), Hederasaponin B (VII) were separated from Clematis tangutica (Maxim.) Korsh. Their cytotoxic activities were evaluated. Saponins IV (new compound) and I showed selective inhibitory activities against HGC-27 with IC50 values of 20.17 and 66.18 µM. Saponin VII exhibited extensive inhibitory action against HGC-27, Hela and SK-OV-3 with IC50 values of 16.47-71.36 µM. Saponin III showed selective inhibitory activity against SK-OV-3 with the IC50 value of 48.70 µM. All isolated saponins were inactive (IC50 >150 µM) to GES-1.

Stearic acid induces CCK and GLP-1 upregulation via GPR120/PLC-ß, leading to reduced appetite in Hu sheep fed with rice straw.

Due to the poor palatability of straw, feeding untreated rice straw reduces ruminant feed intake, thus affecting the production efficiency of animal husbandry. However, the detailed mechanism by which straw affects ruminants' feed intake is unclear. Therefore, this study aimed to elucidate the molecular mechanism by which a rice straw (RS)-based diet affects appetite regulation in Hu sheep. We found that RS promoted the secretion of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) and decreased feed intake. Blood metabolomics showed that RS activated the arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and alpha-linolenic acid metabolism pathways, and the secretion of stearic acid (SA), their metabolic end product, increased significantly. GPR120, one of the classical receptors of long-chain fatty acids (LCFAs), can be involved in appetite regulation. However, the role of SA in satiety hormone regulation mediated by GPR120 in ruminants is unclear. In this study, in vivo experiments showed that in sheep fed with RS, SA increased significantly and activated GPR120/Ca2+, increasing the secretion of the satiety hormones CCK and GLP-1. In vitro mechanism studies showed that SA promotes GLP-1 and CCK secretion by activating GPR120-mediated downstream PKC and IP3R signaling pathways of PLCß.

MSC-ACE2 Ameliorates Streptococcus uberis-Induced Inflammatory Injury in Mammary Epithelial Cells by Upregulating the IL-10/STAT3/SOCS3 Pathway.

In the dairy industry, Streptococcus uberis (S. uberis) is one of the most important pathogenic bacteria associated with mastitis in milk-producing cows, causing vast economic loss. To date, the only real effective method of treating and preventing streptococcal mastitis is antimicrobial therapy. In many inflammatory diseases, mesenchymal stem cells (MSCs) and angiotensin-converting enzyme 2 (ACE2) play an anti-inflammatory and anti-injurious role. Accordingly, we hypothesized that MSCs overexpressing ACE2 (MSC-ACE2) would ameliorate the inflammatory injury caused by S. uberis in mammary epithelial cells more efficiently than MSC alone. By activating the transcription 3/suppressor of cytokine signaling 3 (IL-10/STAT3/SOCS3) signaling pathway, MSC-ACE2 inhibited the NF-κB, MAPKs, apoptosis, and pyroptosis passways. Moreover, MSC-ACE2 overturned the downregulation of Occludin, Zonula occludens 1 (ZO-1), and Claudin-3 expression levels caused by S. uberis, suggesting that MSC-ACE2 promotes the repair of the blood-milk barrier. MSC-ACE2 demonstrated greater effectiveness than MSC alone, as expected. Based on these results, MSC-ACE2 effectively inhibits EpH4-Ev cell's inflammatory responses induced by S. uberis, and would be an effective therapeutic tool for treating streptococcal mastitis.

Retraction Notice to: Silencing of Long Non-coding RNA RP1-93H18.6 Acts as a Tumor Suppressor in Cervical Cancer through the Blockade of the PI3K/Akt Axis.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.041.].

Overexpression of angiotensin-converting enzyme 2 contributes to the amelioration of Streptococcus uberis-induced inflammatory injury in mammary epithelial cells.

Streptococcus uberis (S. uberis) is an environmentally important pathogenic bacterium and is the main pathogenic microorganism responsible for mastitis, which causes significant economic losses worldwide. Currently, there is no particularly effective treatment other than antibiotic therapy. Angiotensin-converting enzyme 2 (ACE2) plays an anti-inflammatory as well as an anti-injury role in numerous inflammatory diseases. Therefore, this study aimed to assess the hypothesis that S. uberis-induced mammary epithelial cells injury associated with ACE2, angiotensin II (Ang II) as well as angiotensin 1-7 (Ang-(1-7)) imbalance and that overexpression of ACE2 can repair S. uberis-induced mammary epithelial cells injury. We observed that the expression level of ACE2 was significantly downregulated after treatment of EpH4-Ev cells with S. uberis. Next, this assay verified the role of ACE2 in S. uberis-induced inflammatory injury in EpH4-Ev cells by overexpressing the ACE2 gene as well as its silencing. The results showed that overexpression of the ACE2 gene significantly activated the interleukin-10/signal transducer and activator of transcription 3/suppressors-of-cytokine-signaling 3 (IL-10/STAT3/SOCS3) pathway, thereby inhibiting the nuclear factor-κB (NF-κB) as well as pyroptosis pathways. Furthermore, overexpression of the ACE2 gene reversed the downregulation of zonula occludens 1 (ZO-1), Occludin, Claudin-1, and Claudin-2 caused by S. uberis, suggesting that ACE2 could promote to repair the blood-milk barrier. However, siRNA silencing of the ACE2 gene produced the opposite effect. These results suggest that ACE2 ameliorates S. uberis-induced mammary epithelial cells injury. AVAILABILITY OF DATA: All data generated or analyzed during this study are included within the article and its additional information file.

Efficient One-Step Separation of Five Flavonoids from the Crude Extract of the Waste Pomace of Sea Buckthorn Berries through Counter-Current Chromatography.

The pomace of sea buckthorn berries is usually discarded when transforming into nonalcoholic or alcoholic beverages, jellies, jams, juices, candies and dairy products. Here, we established a promising approach for one step separation of five flavonoids from the waste pomace of sea buckthorn berries through counter-current chromatography. The crude extract of waste pomace of sea buckthorn berries after juicing was injected into counter-current chromatography with hexane/ethyl acetate/ethanol/water (v/v/v/v, 5:7:5:7) as the solvent system. As a result, five flavonoids, including quercetin, laricitrin, isorhamnetin-7-O-rhamnoside, kaempferol and isorhamnetin, were obtained in a single step separation. Our finding showed that ethanol is a good substitute for methanol to regulate the partition coefficient in hexane/ethyl acetate/ methanol/water system. This study provided a significant measure to utilize the waste pomace of Sea buckthorn berries.

Separation of five flavone glycosides including two groups with similar polarities from Dracocephalum tanguticum by a combination of three high-speed counter-current chromatography modes.

The separation of compounds with similar polarities is challenging. In the present study, five flavone glycosides, including two groups with similar polarities, were obtained from Dracocephalum tanguticum by three high-speed counter-current chromatography modes, including flow rate conversion mode, recycling mode, and heart-cut mode. With flow rate conversion mode, compounds 3 and 4 with similar polarities and compound 5 were separated by high-speed counter-current chromatography with ethyl acetate/methanol/water (5.0% acetic acid) (8:2:10, v/v) system. The flow rate was controlled as: 1.8 mL/min for 0-160 min, 2.2 mL/min for 160-200 min, and 2.5 mL/min for 200-400 min. However, compounds 1 and 2 with similar polarities were not separated due to the similar distributive properties. Then, a recycling and heart-cut mode were introduced to improve the separation efficiency. The heart-cut mode was introduced in the second and third cycles, and compounds 1 and 2 were well separated in the fourth cycle. Consequently, five flavone glycosides, including two groups with similar polarities were obtained and identified as cosmosiin (1), pedaliin (2), quercetin-3-O-rutinoside (3), pedaliin-6''-acetate (4), and sorbifolin-6-O-ß-glucopyranoside (5). The current strategy provides a reference for separating compounds with similar polarities from a crude sample.

Identification of Distinct Molecular Subtypes of Endometrioid Adenocarcinoma.

Endometrial carcinoma (EC) is one of the most common gynecological cancers worldwide. Endometrioid adenocarcinoma (EAC) is the major form of EC, accounting for 75-80% of cases. Currently, there is no molecular classification system for EAC, so there are no corresponding targeted treatments. In this study, we identified two distinct molecular subtypes of EAC with different gene expression patterns and clinicopathologic characteristics. Subtype I EAC cases, accounting for the majority of cases (56%), were associated with an earlier stage, a more well-differentiated grade, a lower tumor invasion rate, and a more favorable prognosis, and the median tumor necrosis percent (15%) was also significantly higher in subtype I EAC. In contrast, subtype II EAC represents high-grade EAC, with a higher tumor invasion rate and tumor weight. The up-regulated genes in subtype I EAC were associated with the immune response, defense response, cell motion, and cell motility pathway, whereas the up-regulated genes in subtype II EAC were associated with the cell cycle, DNA replication, and RNA processing pathways. Additionally, we identified three potential subtype-specific biomarkers, comprising MDM2 (MDM2 proto-oncogene) for subtype I, and MSH2 (mutS homolog 2) and MSH6 (mutS homolog 6) for subtype II.

Effects of a High-Grain Diet With a Buffering Agent on Milk Protein Synthesis in Lactating Goats.

Chinese dairy industries have developed rapidly, providing consumers with high-quality sources of nutrition. However, many problems have also appeared during the development process, especially the low quality of milk. To improve milk quality, a large amount of concentrated feed is usually added to the diet within a certain period of time, which increases the milk production to a certain extent. However, long-term feeding with high-concentration feed can lead to subacute rumen acidosis. Therefore, the present study aimed to determine the effect of adding a buffer on subacute rumen acidosis, and the improvement of milk production and milk quality. We also aimed to study the mechanism of promoting mammary gland lactation. A total of 12 healthy mid-lactating goats were randomly divided into two groups, they were high-grain diet group (Control) and buffering agent group. To understand the effects of high-grain diets with buffers on amino acids in jugular blood and the effects of amino acids on milk protein synthesis, Milk-Testing™ Milkoscan 4000, commercial kits, and high-performance liquid chromatography (HPLC) measurements were integrated with the milk protein rate, the amino acid concentration in jugular venous blood samples, quantitative real-time PCR, comparative proteomics, and western blotting to study differentially expressed proteins and amino acids in mammary gland tissues of goats fed high-grain diets. Feeding lactating goats with buffering agent increased the percentage of milk protein in milk, significantly increased the amino acid content of jugular blood (p < 0.05), and increase the amino acid transporter levels in the mammary gland. Compared with the high-grain group, 2-dimensional electrophoresis technology, matrix-assisted laser desorption/ionization-time of flight/time of flight proteomics analyzer, and western blot analysis further verified that the expression levels of beta casein (CSN2) and lactoferrin (LF) proteins in the mammary glands of lactating goats were higher when fed a high-grain diets and buffers. The mechanism of increased milk protein synthesis was demonstrated to be related to the activation of mammalian target of rapamycin (mTOR) pathway signals.

Machine learning predicts lymph node metastasis of poorly differentiated-type intramucosal gastric cancer.

To construct a machine learning algorithm model of lymph node metastasis (LNM) in patients with poorly differentiated-type intramucosal gastric cancer. 1169 patients with postoperative gastric cancer were divided into a training group and a test group at a ratio of 7:3. The model for lymph node metastasis was established with python machine learning. The Gbdt algorithm in the machine learning results finds that number of resected nodes, lymphovascular invasion and tumor size are the primary 3 factors that account for the weight of LNM. Effect of the LNM model of PDC gastric cancer patients in the training group: Among the 7 algorithm models, the highest accuracy rate was that of GBDT (0.955); The AUC values for the 7 algorithms were, from high to low, XGB (0.881), RF (0.802), GBDT (0.798), LR (0.778), XGB + LR (0.739), RF + LR (0.691) and GBDT + LR (0.626). Results of the LNM model of PDC gastric cancer patients in test group : Among the 7 algorithmic models, XGB had the highest accuracy rate (0.952); Among the 7 algorithms, the AUC values, from high to low, were GBDT (0.788), RF (0.765), XGB (0.762), LR (0.750), RF + LR (0.678), GBDT + LR (0.650) and XGB + LR (0.619). Single machine learning algorithm can predict LNM in poorly differentiated-type intramucosal gastric cancer, but fusion algorithm can not improve the effect of machine learning in predicting LNM.

Mesenchymal Stem Cells Overexpressing ACE2 Favorably Ameliorate LPS-Induced Inflammatory Injury in Mammary Epithelial Cells.

Mesenchymal stem cells (MSCs) are capable of homing injury sites to exert anti-inflammatory as well as anti-damage effects and can be used as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2) plays an important role in numerous inflammatory diseases, but fewer studies have been reported in animal mastitis. We hypothesized that MSCs overexpressing ACE2 is more effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory injury in mammary epithelial cells compared to MSCs alone. The results showed that MSC-ACE2 inhibited the LPS induction by upregulation of TNF-α, IL-Iß, IL-6, and iNOS mRNA expression levels in EpH4-Ev cells compared with MSCs. Furthermore, results showed that both MSC and MSC-ACE2 were significantly activated IL-10/STAT3/SOCS3 signaling pathway as well as inhibited TLR4/NF-κB and MAPK signaling pathways, but MSC-ACE2 had more significant effects. Meanwhile, MSC-ACE2 promoted the expression of proliferation-associated proteins and inhibited the expression of the apoptosis-associated proteins in EpH4-Ev cells. In addition, MSC and MSC-ACE2 reversed the LPS-induced downregulation expression levels of the tight junction proteins in mammary epithelial cells, indicating that both MSC as well as MSC-ACE2 could promote blood-milk barrier repair, and MSC-ACE2 was more effective. These results suggested that MSCs overexpressing ACE2 were more anti-inflammatory as well as anti-injurious action into LPS-induced inflammatory injury in the EpH4-Ev cells. Thus, MSCs overexpressing ACE2 is expected to serve as a potential strategy for mastitis treatment.

[Genetic diagnosis for a patient with Leydig cell hypoplasia caused by two novel variants of LHCGR gene].

OBJECTIVE: To explore the genetic basis for a patient with Leydig cell hypoplasia. METHODS: Whole exome sequencing was used to detect genetic variants in the patient. Suspect variants were verified by PCR and Sanger sequencing of the family members. RESULTS: The patient was found to carry two novel variants, namely c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala), of the luteinizing hormone receptor gene (LHCGR), where were respectively inherited from her father and mother. Upon prenatal diagnosis, the fetus was found to be a heterozygous carrier of the c.265A>T (p.Ile189Leu) variant. CONCLUSION: The compound heterozygous variants of c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala) of the LHCGR gene probably underlie the Leydig cell hypoplasia in the patient.

Separation of five flavonoids with similar polarity from Caragana korshinskii Kom. by preparative high speed counter-current chromatography with recycling and heart cut mode.

Five flavonoids with similar polarity were obtained from Caragana korshinskii Kom. by preparative high speed counter-current chromatography. Due to their similar polarity, it is difficult to select a suitable solvent system for one-step separation. Three fractions including one pure compound were only obtained with a relatively suitable solvent system of ethyl acetate: n-butanol:water (0.5% glacial acetic acid) (4:6:10, v:v:v). In order to improve the separation efficiency, recycling and heart cut modes were introduced. As a result, two flavonoids with separation factor value at 1.13 and the other two with separation factor value at 1.20 were successfully separated. Finally, five flavonoids with purity higher than 98% were obtained. Fortunately, a new compound named myricetin 3'-methyl ether 3-O-glucoside-7-O-rhamnoside was obtained. The results indicated that the recycling combined with heart-cut mode could be effective for the preparation of natural compounds with similar polarity.

Low preoperative serum ALB level is independently associated with poor overall survival in endometrial cancer patients.

Aim: To reveal the prognostic significance of serum albumin (ALB) concentration in endometrial cancer (EC) patients in China. Patients & methods: 345 EC patients were enrolled in a single center, and the preoperative serum ALB concentration were measured. Kaplan-Meier curve analysis and Cox proportional hazards regression model were performed to evaluate the associations between ALB concentration and overall survival (OS) of EC patients. Results: The EC patients with lower preoperative serum ALB concentration exhibited a significantly poorer OS (p < 0.05). Univariate analysis and multivariate analysis indicated that serum ALB concentration was an independent prognostic factor of unfavorable OS for EC patients. Conclusion: Our results showing that ALB concentration may serve as an independent prognostic factor for EC patients.

Silencing of Long Non-coding RNA RP1-93H18.6 Acts as a Tumor Suppressor in Cervical Cancer through the Blockade of the PI3K/Akt Axis.

Cervical cancer (CC) remains a distinct public health stumbling block worldwide. Increasing evidence has highlighted long non-coding RNAs (lncRNAs) as tumor-associated biological molecules. In this study, by means of altering the expression of lncRNA RP1-93H18.6 in CC cells, its ability to influence the biological activities of CC cells was evaluated. Differentially expressed lncRNAs were initially screened from the GEO database. A series of RP1-93H18.6 vectors, small interfering RNA (siRNA) against RP1-93H18.6, and LY294002 (an inhibitor for the phosphatidylinositol 3-kinase [PI3K]/Akt [serine/threonine kinase] axis) were introduced in a respective manner to treat the HeLa cells in order to analyze their effects on cellular activities in vitro. Nude mice with xenograft tumors were utilized in order to assess CC tumor growth and metastasis in vivo. lncRNA RP1-93H18.6 was highly expressed in CC, which could activate the P13K/Akt axis. RP1-93H18.6 vectors exposure increased cell viability, adhesion, migration, and invasion, which resulted in more cells arrested at the S stage and reduced apoptosis, while acting to promote tumor growth and metastasis. The siRNA against RP1-93H18.6 or LY294002 exposure was observed to attenuate the effects induced by RP1-93H18.6 vectors. This study suggests that suppression of lncRNA RP1-93H18.6 exerts potent inhibitory effects on the development and progression of CC via blockade of the PI3K/Akt axis.

Association between TERT promoter mutations and clinical behaviors in differentiated thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: The association between telomerase reverse transcriptase (TERT) promoter mutations and some clinical behaviors in thyroid cancer remains controversial and requires additional investigation. This study aimed to evaluate the association between TERT promoter mutations and clinical behaviors (including clinicopathological features and prognosis) in differentiated thyroid carcinomas (DTC). METHODS: We performed an up-to-date systematic review and current comprehensive meta-analysis. We searched three electronic databases for relevant studies. We used fixed- or random-effect models to calculate pooled estimated odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs). RESULTS: We included 51 eligible studies incorporating 11,382 cases. Average frequencies of TERT promoter mutations in DTC, papillary (PTC), and follicular (FTC) thyroid carcinomas were 10.9%, 10.6%, and 15.1%, respectively. In DTC and PTC, TERT promoter mutations were significantly associated with sex, age, tumor size, vascular invasion, extrathyroidal extension, lymph node and distant metastases, advanced tumor, nodes, and metastasis (TNM) stage, persistence/recurrence, and disease-specific mortality. In FTC, TERT promoter mutations were significantly associated with age, distant metastases, advanced TNM stage, persistence/recurrence, and disease-specific mortality. CONCLUSIONS: TERT promoter mutations could be considered as biomarkers assisting in risk stratification, prognostic prediction, and individualizing therapeutic options for DTC (PTC and FTC).

Effects of High-Grain Diet With Buffering Agent on the Hepatic Metabolism in Lactating Goats.

To gain insight on the effects of a high-grain diet with buffering agent on liver metabolism and the changes of plasma biochemical parameters and amino acids in hepatic vein and portal vein, commercial kit and high performance liquid chromatography (HPLC) were applied to determine the concentration of amino acids of hepatic vein and portal vein blood samples, quantitative real-time PCR and comparative proteomic approach was employed to investigate proteins differentially expressed in liver in lactating dairy goats feeding high-grain diet with buffering agent or only high-grain diet. Results showed that feeding high-grain diet with buffering agent to lactating dairy goats could outstanding increase amino acid content of Gln (p < 0.01), and the amino acid contents of Arg and Tyr in BG were significantly higher (p < 0.05) than that in HG. After adding the buffering agent, the metabolism of amino acids in the liver were changed and most of the amino acids were increasingly synthesized and decreasingly consumed in the liver. In addition, 46 differentially expressed protein spots (≥1.5-fold changed) were detected in buffering group vs. control group using 2-DE technique and MALDI-TOF/TOF proteomics analyzer. Of these, 24 proteins showed increased expression and 22 proteins showed decreased expression in the buffer group vs. control group. Data on Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the high-grain diet with buffering agent alter the expression of proteins related to amino acids metabolism and glycometabolism. In addition, the results conclude that feeding high-grain diet with buffering agent can strengthen anti-oxidant capacity, stress ability, slow down urea metabolism, and alter amino acid metabolism as well as glycometabolism in the liver through different detection methods including proteomic analysis, real-time PCR analysis and biochemical analysis.