Sex Pheromone Receptor-Derived Peptide Biosensor for Efficient Monitoring of the Cotton Bollworm Helicoverpa armigera.

The cotton bollworm, Helicoverpa armigera (H. armigera), causes damage to a wide range of cultivated crops and is one of the pests with the greatest economic importance for global agriculture. Currently, the detection of H. armigera is based on manual sampling. A low limit of detection (LOD), convenient, and real-time monitoring method is urgently needed for its early warning and efficient management. Here, we characterized the amino acid sequence in the sex pheromone receptors (SPRs) recognizing the pheromone components of H. armigera by three-dimensional (3D) modeling and molecular docking. Next, sex pheromone receptor-derived peptides (SPRPs) were synthesized and conjugated to nanotubes by chemical connection. The modified nanotubes were used to fabricate a sensor capable of real-time monitoring of gaseous sex pheromone compounds with a low LOD (∼10 ppb for Z11-16:Ald) and selectivity, and the sensor was able to detect a single live H. armigera. Furthermore, the developed biosensor allowed direct monitoring of the pheromone release dynamics by female H. armigera and showed that the release was instantly reduced in response to light. Here, we report the first demonstration of a biosensing method for detecting gaseous sex pheromones and live H. armigera. The findings show the great potential of the SPRP sensor for broad applications in insect biology study and infestation monitoring.

Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling.

BACKGROUND: PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated. METHODS: By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes. RESULTS: PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell-cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs. CONCLUSIONS: Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.

Ultrasensitive Flexible Olfactory Receptor-Derived Peptide Sensor for Trimethylamine Detection by the Bending Connection Method.

Trimethylamine (TMA) is a harmful gas that exists ubiquitously in the environment; therefore, the sensitive and specific monitoring of TMA is necessary. In this work, we prepared ultrasensitive flexible sensors for TMA detection based on single-walled carbon nanotubes (SWCNTs) and olfactory receptor-derived peptides (ORPs) on low-cost plastic substrates. A novel bending connection method was developed by intentionally bending the interdigitated electrodes with SWCNTs to form a three-dimensional structure during the ORP-connection process, leading to the exposure of more modification sites. The method showed ∼4.7-fold more effective connection amount of the ORPs to SWCNTs compared to the conventional flat-condition connection method. The flexible ORP-SWCNT sensors could significantly improve the limit of detection for gaseous TMA from the reported lowest limit of 10 parts per quadrillion (ppq) to 0.1 ppq. The flexible ORP sensors also exhibited excellent sensitivity to vaporized TMA standards and TMA generated by different kinds of foods under different bending conditions. The results showed that the bending connection method in this work was effective for ultrasensitive flexible ORP sensors and their associated applications.

Kynurenine produced by tryptophan 2,3-dioxygenase metabolism promotes glioma progression through an aryl hydrocarbon receptor-dependent signaling pathway.

The current studies associated with tumor biology continue to describe a high correlation between tryptophan (Trp) metabolism and tumor progression. These findings reflect the complex underlying mechanism of tumor development and highlight the need to explore additional drug targets for carcinoma-associated diseases. In our study, we reported that elevated Trp metabolism was observed in highly malignant glioma tumor tissues from patients. The elevated Trp metabolism in glioma cells were induced by the overexpression of Trp 2,3-dioxygenase 2 (TDO2), which further contributed to the production of the metabolite kynurenine (Kyn). Subsequently, the Kyn derived from Trp metabolism was able to mediate the activation of the aryl hydrocarbon receptor (AhR) and downstream PI3K/AKT signals, resulting in the strengthening of tumor stemness and growth. Meanwhile, the activation of the AhR could promote the process of epithelial-mesenchymal transition in gliomas through a TGF-ß-dependent mechanism, leading to enhanced tumor invasion in vitro and in vivo. Inhibition of the AhR using StemRegenin 1 was demonstrated to suppress glioma growth and improve the outcome of traditional chemotherapy in subcutaneous tumor-bearing mice, representing a promising therapeutic target for clinical glioma treatment.

ATP is not essential for cadaverine production by Escherichia coli whole-cell bioconversion.

ATP plays an essential role in the substrate/product transmembrane transportation during whole-cell bioconversion. This study aimed to address the impact of ATP upon cadaverine synthesis by whole-cell biocatalysts. The results showed no significant change in the ATP content (P = 0.625), and the specific cadaverine yield (P = 0.374) was observed in enzyme-catalyzed cadaverine synthesis with exogenous addition of ATP, indicating that the enzyme-catalyzed process does not require the participation of ATP. Furthermore, a whole-cell biocatalyst co-overexpressed methionine adenosyltransferase (MetK), lysine decarboxylase (CadA), and lysine/cadaverine antiporter (CadB) was constructed and used to investigate the effect of ATP deficiency on the cadaverine production by conversion of L-methionine and L-lysine, simultaneously. The results showed no significant difference (P = 0.585) in the specific cadaverine content between high and low levels of intracellular ATP. In addition, the intra- and extracellular cadaverine concentration and the ratio of ATP/ADP of whole-cell biocatalyst were determined. Results showed that the extracellular cadaverine concentration was much higher than the intracellular concentration, and no significant changes in ATP/ADP ratio during cadaverine synthesis. In contrast, an inhibition effect of the proton motive force (PMF) inhibitor carbonyl cyanide m-chlorophenylhydrazone (CCCP) on cadaverine production was detected. These findings strongly suggest that cadaverine transport in whole-cell biocatalysts was energized by PMF rather than ATP. Finally, a model was proposed to describe cadaverine's PMF-driven transport under different external pHs during whole-cell biocatalysis. This study is the first to experimentally confirm that the cadaverine production by Escherichia coli whole-cell bioconversion is independent of intracellular ATP, which helps guide the subsequent construction of biocatalysts and optimize transformation conditions.

High-performance olfactory receptor-derived peptide sensor for trimethylamine detection based on Steglich esterification reaction and native chemical ligation connection.

Trimethylamine (TMA) commonly exists in daily life and is harmful to human health, therefore the convenient and sensitive monitoring of TMA is highly desired. In this study, we developed a method to fabricate a high-performance TMA sensor by chemically conjugating olfactory receptor-derived peptides (ORPs) to single-walled carbon nanotubes (SWCNTs) on interdigital electrodes. First, the SWCNTs were modified with thioester by Steglich esterification reaction. Next, the ORPs with a cysteine residue at the N-terminus were connected to the thioester by native chemical ligation and modified to the surface of the SWCNTs. The chemical connection method enabled more effective loading of ORPs to the SWCNTs compared to the previously reported physical connection method. Using this approach, the ORPs-SWCNTs sensor for gaseous TMA was fabricated and enabled detection of TMA with a concentration as low as 0.01 parts per trillion, which was three orders of magnitude lower than the reported lowest detection limit up to date. Furthermore, we tested the performance of the ORP-sensor with vaporized TMA and TMA generated from various spoiled food, and the sensor exhibited excellent sensitivity, selectivity, and stability for TMA detection. The results demonstrated the effectiveness of the proposed chemical connection method for the fabrication of ORP-sensor and the great potential of using these sensors for applications in environmental safety, food quality evaluation, and healthcare.

Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 µM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 µM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

Hyperprolactinemia in clinical non-functional pituitary macroadenomas: A STROBE-compliant study.

Hyperprolactinemia is a prevalent endocrine disorder presented in patients with non-functional pituitary adenomas (NFPAs). However, the mechanism involved in hyperprolactinemia in NFPA is not fully illustrated. The current study aims to investigate predictors for hyperprolactinemia in NFPA via analyzing relevant clinical features. Thus, in this study, a cohort of 214 cases with integrated medical records was retrospectively analyzed concerning clinical, pathological, and endocrinological studies before and after surgery.Hyperprolactinemia happened in 93 cases (43.5%). Women (adjust odds ratio [OR] = 3.093; P < .01), age of patients (adjust OR = 0.951; P < .01), and serum free tetraiodothyronine (FT4) level (adjust OR = 0.882; P = .02) were independent predictors for developing preoperative hyperprolactinemia. Tumor size and hypopituitarism had no impact on hyperprolactinemia. During a median follow-up of 43.5 (range, 22-80) months, 83.9% patients with preoperative hyperprolactinemia experienced prolactin (PRL) normalization. Preoperative PRL level (adjusted OR = 1.741, P = .03) was the exclusive predictor for PRL normalization after adjusting for tumor volume, preoperative serum FT4 concentration, and postoperative residual. The PRL normalization rate of patients with lower PRL level (<2.35-fold upper limit of normal range) was 95.2% and decreased to 65.5% for patients with higher PRL level.In conclusion, our results suggest existence of potentially alternative mechanisms underlying hyperprolactinemia in NFPAs, like the discrepancy of sex and age and the negative feedback of FT4. Preoperative PRL is a predictor for postoperative PRL normalization, which is of clinically relevant for postoperative management of NFPAs.

Proliferation, Differentiation and Immunoregulatory Capacities of Brown and White Adipose-Derived Stem Cells from Young and Aged Mice.

BACKGROUND AND OBJECTIVES: Adipose tissue is a source of mesenchymal stem cells, which have the potential to differentiate into various types of cells. Adipose-derived stem cells (ADSCs) are now recognized as an accessible, abundant, and reliable stem cells suitable for tissue engineering and regenerative medicine applications. However, few literatures gave a comprehensive report on the capacities of ADSCs harvested from different sites. Especially, the capacities of ADSCs from aged mice remained unclear. In this study, we investigated several main capacities of brown adipose derived stem cells (B-ADSCs) and white adipose derived stem cells (W-ADSCs) from both young and aged mice. METHODS AND RESULTS: When isolated from young mice, B-ADSCs showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs. Carboxy fluorescein diacetate succinimidyl ester (CFSE) labeling test suggested no significant difference in immunosuppression capacity between B-ADSCs and W-ADSCs. Similarly, no difference between these two were found in several immune related molecules, such as programmed death-ligand 1 (PD-L1), intercellular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), interleukin 10 (IL10), and suppressor of cytokine signaling 1 (socs1). When isolated from aged mice, B-ADSCs also showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs; however, it demonstrated an attenuated immunosuppression capacity compared to W-ADSCs. CONCLUSIONS: In summary, our data showed that ADSCs' characteristics were tissue source dependent and changed with age. It provided evidence for choosing the right tissue-specific ADSCs for clinical application and fundamental research.

Clinical features, radiological findings, and treatment outcomes of high-grade lateral ventricular meningiomas: a report of 26 cases.

High-grade meningiomas in ventricles are rare, where most published series only include a few patients. A retrospective analysis was performed on the clinical features, radiological findings, and treatment outcomes of 26 patients with high-grade meningiomas in lateral ventricles who were surgically treated in our hospital between July 2008 and July 2016. A female predilection (female/male = 1.4:1) was observed with a mean age of 42.4 years. Headache and/or vomiting (65.3%) were the most common initial symptom, and with symptom duration time ranging between 7 days and 5 years (mean 8.5 months). The lateral ventricle trigone area was the most common site (80.7%). Twenty-two patients (84.6%) obtained gross total resection. The 2007 WHO classification was used to classify 22 (84.6%) meningiomas as grade II and the remaining four tumors were graded III. These tumors accounted for a recurrence rate of 38.5% (10 of 26 patients) and a mortality rate of 11.5% (3 deaths) during the follow-up periods. The recurrence rate after the gross total resection was 27.3% (6 of 22 patients). Radiotherapy was administered as an adjuvant treatment in 12 patients (46.2%) after surgery. There were 4 recurrences out of the 12 patients who received radiotherapy and 6 of the 14 patients relapsed without radiotherapy (p = 0.58). The subtotal resection was considered a risk factor for recurrence. The postoperative radiotherapy seemed to have little significance for the high-grade meningiomas in the lateral ventricles. Long-term follow-up is required, regardless of the resection grade, and reoperation is feasible for patients with recurrence.

Glioblastoma Stem Cell-Derived Exosomes Enhance Stemness and Tumorigenicity of Glioma Cells by Transferring Notch1 Protein.

Exosomes contain plenty of bioactive information, playing an important role in intercellular communication by transfer their bioactive molecular contents to recipient cells. Glioblastoma stem cells (GSCs) and non-GSC glioma cells coexist in GBM microenvironment; GSC-released exosomes contain intracellular signaling molecules, which may affect the biological phenotypes of recipient cells. However, whether GSC exosomes could affect the biological phenotype of non-GSC glioma cells has not yet been defined. To explore whether GSC exosomes could reprogramme non-GSC glioma cells into GSCs and its possible mechanism involved, non-GSC glioma cells were treated with GSCs released exosomes; the potential mechanisms of action were studied with RNA interference, Notch inhibitors and Western blot analysis. The proliferation, neurosphere formation, invasive capacities, and tumorigenicity of non-GSC glioma cells were increased significantly after GSC exosome treatment; Notch1 signaling pathway was activated in GSCs; Notch1 protein was highly enriched in GSC exosomes; Notch1 signaling pathway and stemness-related protein expressions were increased in GSC exosome treated non-GSC glioma cells and these cell generated tumor tissues; Notch1 protein expression in GSCs and their exosomes, and the neurosphere formation of GSCs were decreased by Notch1 RNA interference; Notch1 signaling pathway protein and stemness protein expressions were decreased in GSC exosome treated non-GSC glioma cells by Notch1 RNA interference and Notch inhibitors. The findings in this study indicated that GSC exosomes act as information carriers, mediated non-GSC glioma cell dedifferentiation into GSCs by delivering Notch1 protein through Notch1 signaling activation, and enhanced stemness and tumorigenicity of non-GSC glioma cells.

Mammosomatotroph and mixed somatotroph-lactotroph adenoma in acromegaly: a retrospective study with long-term follow-up.

PURPOSE: Although well-documented from pathological aspect, the clinical features and outcomes of acromegaly with mammosomatotroph (MSA) and mixed somatotroph-lactotroph adenoma (MSLA) are seldom reported. Thus, in this study, we analyzed and reported the clinical data about MSAs and MSLAs. METHODS: We retrospectively reviewed medical records of patients with acromegaly in our institution during 2008-2017. Growth hormone (GH)-secreting adenomas were categorized into pure somatotroph adenoma (PSA), MSA and MSLA based on inclusion and exclusion criteria. Clinical information and treatment outcomes during follow-up were analyzed by univariate and multivariate methods. RESULTS: Among 94 patients within this cohort, PSAs, MSAs, and MSLAs accounted for 53, 28 and 13 cases, respectively. MSAs often had smaller size, lower frequency of cavernous sinus invasion and higher gross total resection (GTR) rate. MSLAs were characterized by bigger tumor size, higher frequency of preoperative hyperprolactinemia, and lower GTR rate. Thus, MSLAs had worse long-term biological remission rate than MSAs and PSAs (15.4% vs. 50.0% and 26.4%, p = 0.0371). Gender (male, OR = 0.784, p = 0.011) and tumor volume (OR = 0.784, p = 0.020) were independent predictors for long-term biological remission in binary logistic regression. Subgroup analyses indicated that postoperative nadir GH level (GH-7, HR = 1.242, p = 0.001) was the only risk factor for tumor recurrence for patients with GTR. CONCLUSIONS: Our results provide valuable insights into clinicopathological features of acromegaly. MSAs were relatively smaller lesions with better prognosis. MSLAs were more aggressive with massive size, invasiveness and preoperative hyperprolactinemia. Tumor size and GH-7 were significantly associated with biological remission and tumor relapse after GTR, respectively.

Differential circular RNA expression profiles of invasive and non-invasive non-functioning pituitary adenomas: A microarray analysis.

Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors, and some exhibit locally invasive or even clinically aggressive behavior. Circular RNAs (circRNAs) are a reinvented class of non-coding RNAs that play important roles in tumor initiation and progression.CircRNA microarray assays were performed in 4 invasive and 4 non-invasive NFPAs, and 4 typically differential expression circRNAs were selected for validation using quantitative reverse transcription-polymerase chain reaction. The diagnostic and prognostic values of tested cirRNAs were further evaluated. Bioinformatics analysis and a literature review of potential miRNAs targets involved in pituitary tumor invasion were performed.A specific circRNA expression profile was detected between invasive and non-invasive NFPAs, including 91 upregulated and 61 downregulated circRNAs in invasive tumors. The dysregulation of the 4 circRNAs has been confirmed. The expression of hsa_circRNA_102597, a downregulated circRNA, was significantly correlated with tumor diameter (P < .05) and Knosp grade (P < .01). Hsa_circRNA_102597 alone or in combined with Ki-67 index was able to accurately differentiate invasive from non-invasive NFPAs as well as predict tumor progression/recurrence. Fourteen aberrantly expressed circRNAs might be involved in the invasiveness of pituitary adenomas via seven predicted potential miRNA targets.CircRNAs are participated in pituitary tumor invasion, and may be used as novel diagnostic and prognostic biomarkers in NFPAs.

Giant Prolactinomas: Outcomes of Multimodal Treatments for 42 Cases with Long-Term Follow-Up.

Giant prolactinomas represent a rare entity of pituitary tumors so that the management of these patients is still a prevalent challenge at present. Paying special attention to the treatment strategy and outcomes, we presented a large series of 42 cases looking forward to share our understanding and experience in management of these patients. Male patients accounted for 71.4% of this series and were relatively younger (35.70±2.42 vs. 52.00±3.55 years, p=0.0011) and harbored bigger tumors (14.57 vs. 7.74 cm3, p=0.0179) compared to females. Almost all of these tumors showed suprasellar extension (97.6%) and cavernous sinus invasion (92.9%). Dopamine agonist represented an efficient method to control PRL concentrations (98.8%) and reduce tumor burdens (81.2 %). PRL normalization was detected in 13 out of the 27 patients initially treated with bromocriptine (BRC) whereas none of the 14 patients with first-line operation gained a normalization of PRL concentration after surgery. Although there was no reliable predictor of tumor response, First PRL reduction was a predictive criterion for the nadir PRL level during the long-time period of follow-up for first-line bromocriptine treatment. In conclusion, patients with giant prolactinomas did not gain more benefits from initial surgery. Dopamine agonist (BRC) should be first-line treatment for giant prolactinomas whereas operation merely served as a remedy for acute compression symptoms and dopamine agonist resistance. Consecutive monitoring of serum PRL levels in the early stage of initial BRC treatment is useful for evaluation of therapeutic effect and further therapeutic decision.

Regulation of ATP levels in Escherichia coli using CRISPR interference for enhanced pinocembrin production.

BACKGROUND: Microbial biosynthesis of natural products holds promise for preclinical studies and treating diseases. For instance, pinocembrin is a natural flavonoid with important pharmacologic characteristics and is widely used in preclinical studies. However, high yield of natural products production is often limited by the intracellular cofactor level, including adenosine triphosphate (ATP). To address this challenge, tailored modification of ATP concentration in Escherichia coli was applied in efficient pinocembrin production. RESULTS: In the present study, a clustered regularly interspaced short palindromic repeats (CRISPR) interference system was performed for screening several ATP-related candidate genes, where metK and proB showed its potential to improve ATP level and increased pinocembrin production. Subsequently, the repression efficiency of metK and proB were optimized to achieve the appropriate levels of ATP and enhancing the pinocembrin production, which allowed the pinocembrin titer increased to 102.02 mg/L. Coupled with the malonyl-CoA engineering and optimization of culture and induction condition, a final pinocembrin titer of 165.31 mg/L was achieved, which is 10.2-fold higher than control strains. CONCLUSIONS: Our results introduce a strategy to approach the efficient biosynthesis of pinocembrin via ATP level strengthen using CRISPR interference. Furthermore coupled with the malonyl-CoA engineering and induction condition have been optimized for pinocembrin production. The results and engineering strategies demonstrated here would hold promise for the ATP level improvement of other flavonoids by CRISPRi system, thereby facilitating other flavonoids production.

Enhancing catalytic stability and cadaverine tolerance by whole-cell immobilization and the addition of cell protectant during cadaverine production.

A whole-cell (cadaverine-producing strain, Escherichia coli AST3) immobilization method was developed for improving catalytic activity and cadaverine tolerance during cadaverine production. Cell-immobilized beads were prepared by polyvinyl alcohol (PVA) and sodium alginate (SA) based on their advantages in biocatalyst activity recovery and mechanical strength. The following optimal immobilization conditions were established using response surface methodology: 3.62% SA, 4.71% PVA, 4.21% CaCl2, calcification, 12 h, and freezing for 16 h at - 80 °C, with a cell concentration of 0.3% (g dry cell weight (DCW) per 100 mL) of immobilized beads. After a 2-h bioconversion, the immobilized beads maintained 85% of their original biocatalyst activity, which was 1.8-fold higher than that of free cells. Furthermore, the effects of cell protectants on immobilized biocatalyst activity were examined by fed-batch bioconversion experiments. The results showed that the addition of polyvinylpyrrolidone (PVP) into the immobilized matrix effectively protected biocatalyst activity, with 95% of the relative activity remaining after the 2-h bioconversion. The performance of PVA-SA-PVP-immobilized E. coli AST3 showed continuous production of cadaverine, with an average cadaverine yield of 29 ± 1 g gDCW-1 h-1 after 12 h, suggesting that this method is capable of industrial scale cadaverine production.

Clinical and Pathologic Characteristics Predicted the Postoperative Recurrence and Progression of Pituitary Adenoma: A Retrospective Study with 10 Years Follow-Up.

OBJECTIVE: Tumor recurrence or residual regrowth are poor prognoses for pituitary adenoma (PA). However, there is no validated and well-accepted prognostic classification of PAs to predict the clinical outcome and guide clinical practice. We analyzed the relevant data of a large cohort of patients with PA and thereafter proposed a new clinicopathologic classification for prognostic prediction. METHODS: Tumor recurrence or residual regrowth identified by magnetic resonance imaging scans and endocrine studies were analyzed along with associated clinical and pathological characteristics for patients who underwent surgery in 2008-2016 at West China Hospital. A new clinicopathologic classification was proposed and applied. RESULTS: After a median follow-up of 44.0 months, tumor recurrence and residual progression were identified in 48 (25.0%) and 29 (37.2%) patients, respectively. Proliferative potential (hazard ratio [HR], 2.188; P = 0.002), invasiveness (HR, 1.698; P = 0.029), larger tumor size (HR, 1.029; P = 0.004), high-risk PA subtype (HR, 2.151; P = 0.004), and postoperative residual (HR, 1.941; P = 0.007) were risk factors for recurrence/progression in the early stage after surgery. With respect to clinicopathologic classification, compared with grade 1a tumors, grade 1b, 2a, and 2b adenomas had poorer prognosis with an increased probability of tumor recurrence/progression of 5.133-fold, 4.467-fold, and 20.1-fold, respectively. CONCLUSIONS: The proposed clinicopathologic classification of PAs showed significant value in predicting prognosis and succeeded in identifying cases with more clinically aggressive lesions with recurrence or residual regrowth. This prognostic classification may be helpful when identifying aggressive PAs and deciding the appropriate therapeutic strategy for patients with PAs.

Clinically aggressive phenotype: A clinicopathological case series of atypical pituitary adenomas.

OBJECTIVE: Atypical pituitary adenomas were relatively more malignant lesions defined by WHO criteria. However, not all of them show clinically aggressive behavior. Thus, the current WHO criteria of atypical adenoma didn't seem to be enough to distinguish clinically aggressive adenoma. Therefore, we would like to identify other clinical factors in a cohort of atypical pituitary adenomas to a better identification of clinical aggressiveness. PATIENTS AND METHODS: In order to verify predictors of clinically aggressive phenotype among atypical pituitary adenomas, we retrospectively analyzed the clinical characteristics and therapeutic outcomes of consecutive 49 cases. RESULTS: Totally, 26 cases were identified as clinically aggressive pituitary adenoma. Clinically aggressive lesions were more likely to be functional (46.2% vs. 17.4%, p = .0388) and be detected in males (65.4% vs. 21.7%, p = .0037). Clinically aggressive adenomas also had higher Ki-67 index [5.0 (5.3)% vs. 4.1 (1.3)%, p = .0011] and presented bigger tumor size [11.83 (11.95) cm3 vs. 5.39 (6.08) cm3, p = .0174]. In multivariate analysis, gender (p = .017), functional status (p = .009) and Ki-67 index (p = .024) were independent predictors of clinical aggressiveness. Further analysis revealed that Ki-67 index of more than 4.45% was associated with worse progression-free survival. CONCLUSIONS: Gender, functional status, tumor size and Ki-67 index ≥4.45% were associated with clinical aggressiveness. A clinicopathological classification of pituitary adenomas may be useful to determine who should be under closer radiological follow-up or followed multimodal treatment strategy.

[Postoperative management of patients with sellar tumors through monitoring urine volume and urine electrolytes].

OBJECTIVE: To determine the value of urine volume and urine electrolytes in postoperative management of patients with sellar tumors. METHODS: Medical records of 103 patients with sellar tumors in the West China Hospital from January 2009 to December 2009 were retrospectively reviewed. The patients were managed either based on blood electrolytes (Group A, n = 56) or based on urine volume and urine electrolytes (Group B, n = 47). The incidence of balance disturbance of water and electrolytes was compared between the two groups. RESULTS: The levels of blood electrolytes were normal in both groups 3 days after operations despite significant loss of electrolytes through urine. Balance disturbance of water and electrolytes was revealed 4-7 days after operations. Group B had a lower incidence of balance disturbance of water and electrolytes (17.02%, 8/47) compared with Group A (73.21%, 41/56, P < 0.05). No gender difference in the incidence of balance disturbance of water and electrolytes was found. Higher incidence of balance disturbance of water and electrolytes was found in craniopharyngioma (P < 0.05, vs. pituitary adenoma) and in the patients undergoing craniotomy (P < 0.05, vs. transsphenoidal approach) in Group A, but not in Group B. CONCLUSION: Better management of balance disturbance of water and electrolytes can be achieved for patients with sellar tumors through monitoring urine than through blood. It can also simplify the postoperative management of patients with sellar tumors.