Characteristics and response cutoff of octreotide suppression test in thyrotrophin (TSH)-secreting pituitary adenomas.

CONTEXT: Somatostatin analogs are recommended for preoperative therapy in thyrotrophin secreting pituitary adenomas (TSHomas). Octreotide suppression test (OST) was designed to differentiate TSHomas with resistance to thyroid hormones, while its ability to test the sensitivity of SSA has not been fully studied. OBJECTIVE: To test the sensitivity of SSA in TSHomas with OST. PATIENTS: We collected 48 pathologically confirmed TSHoma patients with complete 72 h' data of OST into analysis. INTERVENTION: Octreotide suppression test. MAIN OUTCOME: Sensitivity timepoint and cutoff of OST. RESULTS: During the entire OST, the TSH descended maximally 89.07% (73.85%, 96.77%), while the FT3 and FT4 declined slowly [43.40% (37.80%, 54.44%) and 26.59% (19.01%, 33.13%), respectively]. The 24th hour was the timepoint wherein the stability occurs for TSH, and the 48th hour for FT3 and FT4 during OST. In the patients who received both short- and long-acting somatostatin analogs (SSA), the 24-h timepoint was the most predictive timepoint for the percentage of TSH decline (Spearman's rank correlation analysis, r = .571, p < .001), while the 72-h timepoint was optimal for predicting the magnitude of TSH decline (Spearman's rank correlation analysis, r = .438, p = .005). In the 24th timepoint, a positive correlation was also observed between TSH suppression rate and the percentage decrease and absolute value decrease of FT3 and FT4. Furthermore, in patients treated with long-acting SSA, the 72-h timepoint was optimal for predicting both the percentage (Spearman's rank correlation analysis, r = .587, p = .01) and magnitude (Spearman's rank correlation analysis, r = .474, p = .047) of TSH decline. The 24th hour was the optimal timepoint with 44.54% (50% of median value of TSH in 72-hOST) decrease of TSH being the observing cutoff. The adverse effect of OST was predominantly occurred in the gastrointestinal system and no severe event occurred during OST. Paradoxical response could occur in OST and it did not influence the effect of SSA as long as sensitivity was confirmed. A high level of hormonal control was achieved in the SSA-sensitive patients. CONCLUSION: OST can be used as an efficient tool to guide the adequate use of SSA.

Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo.

The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to identify covalent inhibitors targeting Pin1's active site Cys113, leading to the development of Sulfopin, a nanomolar Pin1 inhibitor. Sulfopin is highly selective, as validated by two independent chemoproteomics methods, achieves potent cellular and in vivo target engagement and phenocopies Pin1 genetic knockout. Pin1 inhibition had only a modest effect on cancer cell line viability. Nevertheless, Sulfopin induced downregulation of c-Myc target genes, reduced tumor progression and conferred survival benefit in murine and zebrafish models of MYCN-driven neuroblastoma, and in a murine model of pancreatic cancer. Our results demonstrate that Sulfopin is a chemical probe suitable for assessment of Pin1-dependent pharmacology in cells and in vivo, and that Pin1 warrants further investigation as a potential cancer drug target.

Plasma fibronectin can affect the cytokine profile and monocytes/macrophages function in addition to predicting the prognosis of advanced sepsis.

The value of plasma fibronectin (pFN) in the diagnosis and prognosis of sepsis has not been fully established. Previous studies finding that pFN is significantly reduced in sepsis, however, whether reduced pFn affects the prognosis of sepsis has not been clarified. Here, we detected and analyzed pFN and other conventional inflammatory markers in advanced sepsis patients and performed correlation analysis with SOFA score. We also used Fn gene conditional knockout mice which were performed by cecum ligation and puncture (CLP) to investigate the effect of FN deficiency on sepsis prognosis. We found, compared with procalcitonin, c-reactive protein, and interleukin-6, pFN was more correlated with SOFA score in advanced sepsis patients (r -.720, p < .001). In animal experiments, Fn gene knockout mice showed significantly greater mortality after CLP compared with the control group because of inhibited phagocytosis and bacterial clearance ability of macrophages, with double cytokine storm. Furthermore, FN can regulate macrophages through the integrin α5ß1/Fak/Src signaling pathway. Overall, we found pFN can more accurately reflect the severity and prognosis of advanced sepsis. The absence of FN altered the cytokine storm and phagocytic function of macrophages, suggesting that FN could be a potential therapeutic target in sepsis.

Familial dysalbuminemic hyperthyroxinemia combined with Graves' disease: a rare case report.

BACKGROUND: Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disease characterised by an abnormally increased affinity of albumin for serum thyroxine. Assay interference and differential diagnosis remain challenging for FDH. The condition is more complicated when FDH is combined with primary thyroid diseases. Co-occurrence of FDH and Graves' disease is rare. CASE PRESENTATION: We report the case of a 28-year-old woman with complex FDH and coexisting Graves' disease. Initially, the existence of FDH was not recognised. Graves' disease was relieved after treatment with antithyroid drugs and two administrations of radioactive iodine therapy. She subsequently developed primary hypothyroidism and was prescribed levothyroxine replacement. However, thyroid function failed to normalise despite frequent levothyroxine dose adjustments. Ultimately, syndromes involving the inappropriate secretion of thyroid-stimulating hormone (IST) were considered, and FDH was successfully differentiated from other causes of IST. CONCLUSIONS: A greater focus on FDH when investigating the causes of IST is critical to correctly evaluate thyroid function status and avoid inappropriate treatment, especially in complicated cases with concurrent FDH and primary thyroid diseases.

Identification of a potent and selective covalent Pin1 inhibitor.

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is commonly overexpressed in human cancers, including pancreatic ductal adenocarcinoma (PDAC). While Pin1 is dispensable for viability in mice, it is required for activated Ras to induce tumorigenesis, suggesting a role for Pin1 inhibitors in Ras-driven tumors, such as PDAC. We report the development of rationally designed peptide inhibitors that covalently target Cys113, a highly conserved cysteine located in the Pin1 active site. The inhibitors were iteratively optimized for potency, selectivity and cell permeability to give BJP-06-005-3, a versatile tool compound with which to probe Pin1 biology and interrogate its role in cancer. In parallel to inhibitor development, we employed genetic and chemical-genetic strategies to assess the consequences of Pin1 loss in human PDAC cell lines. We demonstrate that Pin1 cooperates with mutant KRAS to promote transformation in PDAC, and that Pin1 inhibition impairs cell viability over time in PDAC cell lines.

Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of mRNA splicing relevant proteins in aging HSPCs.

BACKGROUND: HSPC (hematopoietic stem/progenitor cell) aging was closely associated with the organism aging, senile diseases and hematopoietic related diseases. Therefore, study on HSPC aging is of great significance to further elucidate the mechanisms of aging and to treat hematopoietic disease resulting from HSPC aging. Little attention had been paid to mRNA splicing as a mechanism underlying HSPC senescence. RESULTS: We used our lab's patented in vitro aging model of HSPCs to analyze mRNA splicing relevant protein alterations with iTRAQ-based proteomic analysis. We found that not only the notable mRNA splicing genes such as SR, hnRNP, WBP11, Sf3b1, Ptbp1 and U2AF1 but also the scarcely reported mRNA splicing relevant genes such as Rbmxl1, Dhx16, Pcbp2, Pabpc1 were significantly down-regulated. We further verified their gene expressions by qRT-PCR. In addition, we reported the effect of Spliceostatin A (SSA), which inhibits mRNA splicing in vivo and in vitro, on HSPC aging. CONCLUSIONS: It was concluded that mRNA splicing emerged as an important factor for the vulnerability of HSPC aging. This study improved our understanding of the role of mRNA splicing in the HSPC aging process.

Mannotriose induced differentiation of mesenchymal stem cells into neuron-like cells.

This article demonstrates that mannotriose effectively induces the differentiation of mesenchymal stem cells into neuron-like cells in vitro. Rat-derived mesenchymal stem cells were investigated on their potential to differentiate into neuron-like cells induced by mannotriose purified from Radix Rehmanniae Preparata in vitro. The percentage of the neuron-specific enolase positive cells and the Nissl positive cells after mannotriose treatment was increased. The mRNA levels of neurofilament medium and neuron-specific enolase were upregulated in the mannotriose group compared to the control. These findings demonstrate that mannotriose purified from Radix Rehmanniae Preparata can effectively induce differentiation of rat-derived mesenchymal stem cells into neuron-like cells.

Cosecreting TSH/GH pituitary adenomas-an 8-year experience in a single tertiary center.

PURPOSE: Thyrotropin-secreting pituitary adenoma is a rare disorder and was recently classified as an aggressive tumor in the World Health Organization guidelines. The number of available studies on cosecreting thyrotropin/growth hormone pituitary adenoma is especially limited. METHODS: A single-center retrospective analysis of patients with thyrotropin/growth hormone pituitary adenoma was performed at Peking Union Medical College Hospital, one of the largest pituitary care centers in China, from January 2012 to January 2020. Additionally, data about cosecreting thyrotropin/growth hormone pituitary adenoma were collected and analyzed. The diagnosis, therapy and follow-up were all compared to that of solo-secreting thyrotropin pituitary macroadenoma. RESULTS: Twelve patients (10.81%) were identified with thyrotropin/growth hormone pituitary adenoma at Peking Union Medical College Hospital within 8 years, all of which were classified as macroadenoma. Compared with solo-secreting thyrotropin pituitary macroadenoma, thyrotropin/growth hormone pituitary adenoma presented with a higher proportion of cavernous sinus invasion (50%) and had a larger maximum tumor diameter. The patients had a lower surgical complete remission rate and a worse prognosis. Interestingly, they revealed a striking phenomenon of "solo part remission". CONCLUSIONS: Thyrotropin/growth hormone pituitary adenoma is rare. Some patients do not present with the typical manifestations; however, the possibility of a cosecretion tumor should not be excluded. A preoperative comprehensive evaluation of anterior pituitary hormones is necessary. Thyrotropin/growth hormone pituitary adenoma revealed a high tendency of invasion, and the prognosis of patients with thyrotropin/growth hormone pituitary adenoma was poor. If necessary, timely postoperative drug administration or radiotherapy should be carried out.

[Clinical Characteristics of Lipoic Acid-mediated Insulin Autoimmune Syndrome in Two Patients with Type 2 Diabetes Mellitus].

This article summarizes the clinical features and follow-up findings of insulin autoimmune syndrome in two patients with type 2 diabetes after the use of lipoic acid,along with literature review,with an attempt to increase the awareness of lipoic acid-induced insulin autoimmune syndrome among clinicians and improve its diagnosis and treatment.

Microarray analysis of long-noncoding RNAs and mRNA expression profiles in human steroid-induced avascular necrosis of the femoral head.

This study performed the first microarray analysis of long-noncoding RNA (lncRNA) and mRNA expression profiles in human steroid-induced avascular necrosis of the femoral head (SAVNFH). Expression levels of lncRNAs and mRNAs in three human SAVNFH samples and three human femoral head fracture samples (controls) were detected using third-generation lncRNA microarrays (KangChen Biotech, Shanghai, China). The fold change, false discovery rate, and P value were utilized to filter genes with significant differential expression in the SAVNFH samples compared with the control samples. In total, there were 1179 upregulated and 3214 downregulated lncRNAs (P2. zerofold, P < 0.05). Meanwhile, 1092 upregulated and 565 downregulated mRNAs were found in the SAVNFH samples compared with the control samples. Then, quantitative real-time polymerase chain reaction was used to confirm the previous microarray results using 8 and 20 selected dysregulated lncRNAs and mRNAs, respectively, and the results generally confirmed the microarray findings. Finally, we used Gene Ontology (GO) and pathway analysis to investigate the functions of the altered mRNAs and their associated GO terms and biological pathways. The Immune system process term (GO:0002376) was the most significantly upregulated GO term, and the Regulation of blood coagulation term (GO:0030193) was the most significantly downregulated GO term in the biological process category for the SAVNFH samples. "Hematopoietic cell lineage - Homo sapiens (human) (Pathway ID: hsa04640)" and "Complement and coagulation cascades - Homo sapiens (human) (Pathway ID: hsa04610)" were the most significantly up- and downregulated pathways in the SAVNFH samples compared with the controls. In conclusion, the differential expression of lncRNAs and mRNAs may be correlated with the pathogenesis of SAVNFH, and these significantly dysregulated lncRNAs and mRNAs may function through networks or participate in several specific biological processes. Further research is needed to understand their exact functions and mechanisms in SAVNFH.

RNA-Seq analysis of differentially expressed genes relevant to mismatch repair in aging hematopoietic stem-progenitor cells.

We used RNA-sequencing (RNA-Seq) technology and an old hematopoietic stem and progenitor cells (HSPCs) model in vitro to analyze differential expressions of mismatch repair (MMR)-related genes in aged HSPCs, so as to explore the mechanism of DNA MMR injury in hematopoietic stem cells (HSC) aging. In this study, by combining RNA-seq data and National Center for Biotechnology Information database, we focus on six widely reported MMR genes MSH2, MSH3, MSH6, MLH1, PMS1, PMS2, and five MMR genes with closer ties to HSC aging Pcna, Exo1, Rpa1, Rpa2, and Rpa3 according to the genes functional classification and the related signaling pathway. It is concluded that MMR is closely related to HSC aging. This study provides experimental evidence for future researching MMR in HSC aging.

URINARY IODINE CONCENTRATION IS INVERSELY ASSOCIATED WITH THYROGLOBULIN ANTIBODIES.

Objective: Epidemiologic studies on the relationship between iodine and thyroid antibodies are inconsistent. Iodine nutrition, genetic, and environmental factors have been shown to modify the effects of iodine on thyroid autoimmunity. We investigated the relationship between urinary iodine concentration (UIC) and thyroglobulin antibodies (TgAbs) in individuals living in iodine-sufficient areas in this cross-sectional study. Methods: A total of 15,008 participants were recruited according to the age range of the population of China in our study. An oral questionnaire was administered to collect basic demographic information. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAbs), TgAbs, and UIC were measured, and thyroid ultrasonography was performed in all subjects. Participants were further divided according to the level of UIC and the status of TgAb, and logistic regression was applied to determine the relationship between UIC and TgAbs. Results: The median UIC of the study population was 205.23 (95% confidence interval [CI], 65.7 to 537.67) µg/L. A total of 17.6% of participants had UIC <100 µg/L. With the increase in UIC, the prevalence of positive TgAbs decreased gradually. UIC level was lowest in subjects with high TgAb titer (median, 182.36 µg/L; 95% CI, 52.88 µg/L to 506.71 µg/L) and highest in the TgAb-negative group (median, 207.16 µg/L; 95% CI, 66.94 µg/L to 538.72 µg/L). Multilinear correlation analysis showed that gender (ß = 37.632; P<.001), age (ß = 0.467; P = .038), TSH (ß = 13.107; P<.001), TPOAb (ß = 1.150; P<.001), thyroid volume (ß = 2.883; P<.001), and UIC (ß = -0.047; P = .032) were independent predictors of TgAb variations. Low UIC (<100 µg/L) was associated with increased risk of positive TgAbs (adjusted odds ratio = 1.255 [1.004 to 1.568]). Conclusion: Low UIC is an independent risk factor for positive TgAb in individuals living in iodine-sufficient areas. Abbreviations: CI = confidence interval; CV = coefficient of variation; FT3 = free triiodothyronine; FT4 = free thyroxine; OR = odds ratio; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyrotropin; UIC = urinary iodine concentration; USI = universal salt iodization.

[Clinical manifestations, therapeutic response to tyrosinase inhibitor and RET gene activating mutation in a patient with multiple endocrine neoplasia 2B].

OBJECTIVE: To explore the clinical manifestations, therapeutic response and RET gene mutation in a patient with multiple endocrine neoplasia 2B (MEN2B) characterized by medullary thyroid carcinoma (MTC), bilateral adrenal pheochromocytoma and multiple mucosal neuromas. METHODS: The clinical features, laboratory data and radiological manifestations of this patient were collected. Genomic DNA was extracted from her peripheral blood leukocytes and her parents. Tenth to sixteenth exons of RET proto-oncogene, including the flanking regions of introns, were amplified by polymerase chain reaction (PCR). And the mutations of RET proto-oncogene were identified by direct sequencing. RESULTS: MEN-2B was diagnosed by the clinical presentations, laboratory tests and radiological findings. Gene analysis confirmed heterozygous mis-sense mutation at codon 918 in exon 16 of RET proto-oncogene in which thymine was replaced by cytosine (ATG→ACG). Her thyroid medullary carcinoma was treated by radical operations and radiotherapy. Tyrosinase inhibitor sorafenib was administered for 2 months and watery diarrhea and cough were alleviated. The drug was withdrawn because of such intolerant side effects as hair loss and painful rashes. She had a survival time of over 14 years with multiple system tumor metastases. CONCLUSIONS: The mutation analysis of RET proto-oncogene confirmed the diagnosis of MEN2B in respect of molecular genetics. For patients with advanced MTC, tyrosinase inhibitors may relieve the symptoms and provide a new therapeutic choice.

[Relationship between maternal milk and serum thyroid hormones in patients with thyroid related diseases].

OBJECTIVE: To explore the relationship between maternal milk and serum thyroid hormones in patients with thyroid-related diseases. METHODS: Serum and breast milk samples were collected from 56 breastfeeding mothers. Milk and serum free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine(T3), thyroxine (T4), and thyrotrophin (TSH) were determined, and T3/T4 was calculated. Using the serum thyroid hormones as the independent variables and milk thyroid hormones as the dependent variables, we performed linear regression analysis. RESULTS: The milk FT3, FT4, T3, T4, TSH, and T3/T4 were (2.30 ± 0.82) pg/ml ,(0.45 ± 0.26) ng/dl, (0.35 ± 0.20) ng/ml, (2.96 ± 1.55) Μg/dl, (0.12 ± 0.08) ΜU/ml, and 0.12 ± 0.04, respectively. Milk FT3 (r = 0.778, P = 0.000), T3 (r = 0.603, P = 0.000), T4 (r = 0.485, P = 0.004), and TSH (r = 0.605, P = 0.000) concentrations were positively correlated with those in serum. CONCLUSION: Thyroid hormones are present in human milk and are positively correlated with those in serum.

Thyroid dysfunction after immune checkpoint inhibitor treatment in a single-center Chinese cohort: a retrospective study.

BACKGROUND: Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanisms remain unclear. PURPOSE: To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. METHODS: We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. RESULTS: The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient thyrotoxicosis), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to first clinical presentation was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.67; P < 0.001), previous thyroid disease (OR 4.30, 95% CI 1.54-11.99; P = 0.005), and a higher baseline thyroid-stimulating hormone level (OR 2.76, 95% CI 1.80-4.23; P < 0.001). Thyrotoxicosis was only associated with the baseline thyroid-stimulating hormone (TSH) level (OR 0.59, 95% CI 0.37-0.94; P = 0.025). Thyroid dysfunction after initiation of ICI therapy was associated with better progression-free survival (hazard ratio [HR] 0.61, 95% CI 0.44-0.86; P = 0.005) and overall survival (hazard ratio 0.67, 95% CI 0.45-0.99; P = 0.046). Anti-thyroglobulin antibody positivity increased the risk of thyroid irAEs. CONCLUSIONS: The occurrence of thyroid irAEs with diverse phenotypes is common. Distinct clinical and biochemical characteristics suggest heterogeneity among different subgroups of thyroid dysfunction, which requires further research to explore the under mechanism.

Using preoperative ultrasound vascularity characteristics to estimate medullary thyroid cancer.

BACKGROUND: The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. METHODS: Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as "ultrasound-high suspicious" (h-MTC) and "ultrasound-low suspicious" (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. RESULTS: We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P < 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (87.1% vs. 32.3%, P < 0.001)) and CHEN IV patterns (penetrating vascularity) (100% vs. 25.8%, P < 0.001) were found in l-MTC than benign nodules. CONCLUSIONS: Vascularity features can help differentiate l-MTC from benign nodules; moreover, we report a novel sonographic vascularity pattern of l-MTC disease, penetrating branching vascularity. The utilization of vascularity features will help to identify MTC among nodules with low-intermediate suspicion by ultrasound risk classification to ensure appropriate clinical management.

[Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors].

OBJECTIVE: To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma. METHODS: Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR). RESULTS: Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05). CONCLUSION: Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Magnetic resonance imaging findings of pituitary hyperplasia due to primary hypothyroidism.

OBJECTIVE: To explore the clinical and magnetic resonance imaging (MRI) findings of pituitary hyperplasia due to primary hypothyroidism. METHOD: The clinical presentations, laboratory examinations, and MRI findings of 11 patients with pituitary hyperplasia secondary to primary hypothyroidism diagnosed at our hospitals from the beginning of 2008 to the end of 2011 were retrospectively reviewed. RESULTS: The clinical manifestations in 11 patients included growth arrest(7/8), mental retardation (6/8), cold intolerance and fatigue(6/11), slightly increased body weight (6/11), galactorrhea (3/11), paramenia (8/9), precocious puberty companying vaginal bleeding (2/2),and blurry vision (3/11). Laboratory investigations revealed grossly increased thyroid stimulating hormone, decreased thyroxine, and slightly elevated prolactin levels in all cases. Thyroid antibody was positive in six cases. On MRI, pituitary mass were detected a large intrasellar with/without suprasellar extension in all patients,showing the characteristic of symmetric enlargement. Spherical shape was viewed in 5 cases,with the height of (12.22 ± 3.12)mm. In the other 6 cases, the pituitary mass with the shape of calabash extended superiorly to suprasellar area, with a height of(18.95 ± 2.23)mm. The signal of pituitary mass was isointense to grey matter both on T1 weighted imaging and T2 weighted imaging. Bright short T1 signal in posterior lobe of pituitary was visible. Pituitary stalk was detected only in 4 cases from MRI without dislocation, while the width of pituitary stalk was within the normal limit. CONCLUSIONS: Pituitary hyperplasia should be considered when homogenous enlargement of the pituitary gland is found on MRI. The integration of MRI findings, clinical manifestations, and laboratory findings is helpful for the proper identification of the primary endocrine disease and thus avoid misdiagnosis.

Combination of transsphenoidal endoscopic surgery and presurgical somatostatin analogs in thyrotropin (TSH)-secreting pituitary adenomas: Treatment outcome and long-term remission at a single pituitary center.

Background: Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) account for an extremely rare group of pituitary adenomas. Few studies examined the sensitivity and efficacy of presurgical somatostatin analogs (SSAs) and described the long-term remission under such treatment modality. The aim of the present study was to assess the efficacy of presurgical SSA treatment and long-term remission after surgery. Methods: A retrospective cohort of 65 TSHoma patients who received endoscopic transsphenoidal pituitary surgery between 2011 and 2020 in a single pituitary center in China was established. Data were analyzed for sex differences and different types of SSA and ultimately to explore the hormonal cutoff for remission prediction. Results: TSHomas had a predominant female preference in this cohort (43 women vs. 22 men). Baseline FT3 was higher in men [7.543 ± 2.407 vs. 5.58 (4.99, 6.58), p = 0.019], which was consistent with its longer diagnosis time and larger tumor volume. The median medication time for hormonal control was 2. 5 days for short-acting SSA and 4. 0 weeks for long-term SSA. Patients with long-acting SSA had a shrinking maximum tumor diameter at a median of 1.0 (-1.6, 4.925) mm. Only 10 patients (15.38%) were not in complete remission among whom 8 patients were not en-bloc resected and 2 patients had tumor recurrence after 81.6 and 10. 7 months of complete removal. Postsurgical thyroid hormones (within 1 week) of TSH <0.094 µIU/ml were identified as the cutoff for remission using the ROC curve. Conclusions: The combination of endoscopic transsphenoidal surgery and presurgical SSA TSHomas provided a higher long-term remission for TSHomas.