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To develop a digital breast tomosynthesis (DBT)-based radiomics nomogram for preoperative evaluation of lymphovascular invasion (LVI) status in patients with invasive breast cancer (IBC).A total of 135 patients with pathologically confirmed IBC who underwent preoperative DBT from July 2018 to May 2020 were retrospectively enrolled and randomized into the training and validation sets. Radiomics feature extraction was performed on the volume of interest (VOI) manually outlined. A four-step algorithmic was applied to screen the features with the highest predictive power in the training set for constructing the radiomics signature and calculating the correspondent radiomics score (Rad-score). Logistic regression analyses were utilized to develop a combined radiomics model that incorporated the DBT-reported clinicoradiological semantic features and Rad-score, which was visualized as a radiomics nomogram.The percentage of LVI-positive patients was 60.2% and 59.5% in the training and validation sets, respectively. The radiomics signature was constructed based on nine features selected from the 1218 radiomics features extracted. Higher Rad-score, maximum tumor diameter, and spiculate margin were independent risk factors for LVI. The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity of the radiomics nomogram were 0.905, 72.7%, and 94.6% in the training set, and 0.835, 80.0%, and 76.5% in the validation set, respectively; this data was higher than models incorporating clinicoradiological semantic features alone or the radiomics signature in both sets.Preoperative DBT-based combined radiomic nomogram could be a potential biomarker for LVI in patients with IBC.

Objectives The Wnt signalling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients. Methods We recruited 77 patients newly diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. Wnt antagonists [sclerostin (SOST), dickkopf-related protein 1 (DKK-1), and Wnt inhibitory factor 1 (WIF-1)], bone turnover markers [osteocalcin, procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX)] and the bone remodelling index were investigated at baseline and posttreatment. Results Acromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodelling index than controls (all P < 0.01). Serum SOST, DKK-1 and WIF-1 levels were significantly decreased in acromegalic patients compared to controls (all P < 0.01). Serum SOST and WIF-1 levels correlated negatively with growth hormone levels; SOST levels were positively correlated with WIF-1. Posttreatment, serum bone turnover markers and the bone remodelling index decreased, while SOST and WIF-1 significantly increased (P < 0.05). DKK-1 levels did not change compared to baseline (P > 0.05). In biochemically controlled patients, SOST, WIF-1 and bone turnover markers almost reached normal levels (all P > 0.05). Conclusion Patients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists might be involved in the compensatory mechanism of increased bone fragility in active acromegaly. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and challenging management. The present study aimed to investigate the expression of programmed death ligand-1 (PD-L1) and V-domain Ig-containing suppressor of T cell activation (VISTA) in ACC and their associations with clinicopathological features and survival outcomes. Immunohistochemistry was performed on formalin-fixed paraffin-embedded specimens from 54 ACC patients. Chi-square/Fisher’s exact tests or independent samples t/Mann–Whitney U tests were performed to assess correlations between immunoscores and clinicopathological parameters. The Kaplan–Meier method and Cox regression were conducted for survival analysis and to identify independent predictors of overall (OS) and disease-free (DFS) survival. Results showed that VISTA was expressed in tumor cells (TCs) and tumor-infiltrating immune cells (TICs) in 81.5% (44/54) and 40.7% (22/54) of the patients, respectively. PD-L1 positivity was found in either TCs or TICs in 11.1% (6/54) of the patients. Patients with positive VISTA expression in TCs had a higher tumor stage (56.9% vs 20%, P = 0.036) and Ki-67 index (30.50 ± 23.51% vs 14.76 ± 11.75%, P = 0.006). However, PD-L1 positivity in either TCs or TICs had no association with patient clinicopathological features. A higher VISTA expression intensity, a larger area and a higher immunoscore were associated with increased risks of disease progression and overall mortality, but PD-L1 expression in TCs or TICs was not associated with OS or DFS. In conclusion, positive TC VISTA expression was correlated with pathological parameters related to malignancy in ACC patients. This finding provides novel evidence of the value of VISTA, in addition to PD-L1, as an immunotherapeutic target in ACC.

The severe pollution caused by antibiotics has prompted considerable concerns in recent decades. In this study, the Bi

The aim was to examine changes in the bone-derived hormone lipocalin 2 (LCN2) levels in patients with active acromegaly and to investigate the potential roles of LCN2 and osteocalcin in glucose metabolism. We recruited 50 consecutive acromegalic patients. Of those, 39 patients with complete postoperative follow-up data were included. Thirty sex-, age-, and BMI-matched healthy individuals were recruited as normal controls. The pre- and postoperative serum LCN2 and osteocalcin levels were compared. The homeostasis model assessment insulin resistance (HOMA-IR) index and secretion [β-cell function (HOMA-β)] were calculated. Compared with controls, acromegalic subjects had lower LCN2 levels (34.15 ± 9.95 vs 57.50 ± 29.75 ng/mL, P

The existing evidence about the impact of bridging therapy (BT) on chimeric antigen receptor (CAR)-T cell therapy in patients with large B cell lymphoma (LBCL) is conflicting. Therefore, we reviewed all available evidence to examine the association between BT and CAR-T therapy outcomes by systematic review and meta-analysis approach.Two reviewers independently searched Embase, PubMed, Web of Science, and Cochrane library to identify all records that described BT for LBCL treated with CAR-T. We then applied a fixed- or random-effects meta-analysis to estimate the pooled hazard ratios (HRs) and rate ratio (RRs) for efficacy and safety endpoints and assessed differences across various BT modalities. The Newcastle-Ottawa Scale was used to evaluate study quality.Twenty-six reports from 24 studies involving 2014 patients were included in the analysis. Pooled results showed that patients requiring BT had significantly worse 1-year overall survival rate (RR = 0.76, 95% confidence interval [CI] 0.68-0.85, P0.001), 1-year progression-free survival rate (RR = 0.71, 95% CI 0.60-0.85, P0.001), progression-free survival (HR = 1.35, 95% CI 1.07-1.69, P = 0.01), overall response rate (RR = 0.88, 95% CI 0.81-0.95, P = 0.001), complete response rate (RR = 0.78, 95% CI 0.65-0.93, P = 0.005), and grade ≥3 immune effector cell-associated neurotoxicity syndrome (RR = 1.43, 95% CI 1.10-1.87, P = 0.007), and tended to have poorer overall survival (HR = 1.42, 95% CI 0.99-2.02, P = 0.056) and grade ≥3 cytokine release syndrome (RR = 1.59, 95% CI 0.92-2.75, P = 0.096). Prolonged cytopenias were the common toxicity event associated with BT. Radiotherapy may serve as a promising BT option that can provide safe and effective disease control for patients with LBCL before CAR-T infusion. The inconsistency of patient baselines in the current study hindered further comparisons between different BT modalities. Most of the available evidence was rated as low quality because of concerns over low comparability.BT appears to be associated with comparatively poor efficacy and safety outcomes after CAR-T infusion. However, due to the considerable heterogeneity between the BT and non-BT cohorts at disease baseline, no definitive conclusions can be made for the true impact of BT on CAR-T until further randomized studies are conducted.

Preeclampsia is a common syndrome in pregnancy and a leading cause of mortality of pregnant females and their infants. To investigate the diagnostic and prognostic utility of lncRNA T-cell leukemia/lymphoma 6 (TCL6) in patients with preeclampsia, 120 singleton pregnant females with preeclampsia and another 100 healthy pregnant control subjects were analyzed in the present study. The expression of lncRNA TCL6 in the serum of the included patients was detected. Receiver operating characteristic curve analysis was applied to evaluate the efficiency of lncRNA TCL6 in terms of preeclampsia diagnosis and grading. Kaplan-Meier analysis was adopted to assess the effect of lncRNA TCL6 expression on the rate of adverse pregnancy. Multivariate logistic regression was used to determine high-risk factors of adverse pregnancy. The results indicated that lncRNA TCL6 was significantly increased in the serum of patients with preeclampsia. Furthermore, TCL6 was elevated in subgroups of patients with early-onset or severe preeclampsia and with Haemolysis, Elevated Liver enzymes and Low Platelet count syndrome in comparison with other patients with preeclampsia. High expression of TCL6 in pregnant females corresponded to a higher rate of adverse pregnancy outcomes. Severe preeclampsia, early-onset preeclampsia and high TCL6 expression were identified as independent risk factors for adverse pregnancy outcomes. For each unit increase in TCL6 expression, a 9.5-fold increase of the risk of adverse maternal and fetal outcomes was determined. Collectively, high expression of lncRNA TCL6 may assist the diagnosis and grading of preeclampsia and may be adopted as an independent risk factor for adverse pregnancy outcomes.

The Wnt signaling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients.We recruited 77 patients recently diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. At baseline and posttreatment, Wnt antagonists (sclerostin [SOST], dickkopf-related protein 1 [DKK-1], and Wnt inhibitory factor 1 [WIF-1]), bone turnover markers (osteocalcin, procollagen type 1 N-terminal propeptide [P1NP], and C-terminal telopeptide of type 1 collagen [CTX]) and the bone remodeling index were investigated.Acromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodeling index than controls (P.01). Serum SOST, DKK-1, and WIF-1 levels were significantly decreased in patients compared to controls (all P.01). Serum SOST and WIF-1 levels were negatively correlated with growth hormone levels; SOST levels were positively correlated with WIF-1. After treatment, serum bone turnover markers and the bone remodeling index decreased, while SOST and WIF-1 significantly increased (P.05). DKK-1 levels did not change compared to baseline (P.05). In biochemically controlled patients, SOST and WIF-1 levels and bone turnover markers were restored and did not differ from those of the control participants (all P.05).Patients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists is a compensatory mechanism to counteract increased bone fragility in active acromegaly.

The contamination of heavy metals (HMs) in the environment has aroused a global concern. The valid remediation of HM contaminated environment is a highly significant issue. As alternative to carbon materials, biochar has been vastly documented for the remediation of HM contaminated environment. However, there are some possible imperfections to meet the actual remediation tasks as the finite properties of raw biochar, and the remediation process is complex and unexpectedly. This review focuses on the progress made on environmental HM remediation by biochar-based materials within the past six years. The property analysis and key modifications of biochar are summarized inspired by their applicability or necessity for HM decontamination, and the environmental remediation as well as the implicated mechanisms are thoroughly elaborated from multiple pivotal sides. The evaluations of practical application associated with biochar amendment are also presented. Finally, some pertinent improvements and research directions are proposed. To our knowledge, this article is the first time to make a systematic summary on the reliability and practicability of biochar-based materials for environmental HM remediation, and critically pointed out the existing issues to facilitate the judicious design of biochar-based materials and understanding the research trends. It is also aims to provide reference for subsequent research and propel the practical applications.

BackgroundCurrently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.MethodsTwo reviewers independently searched the Embase, PubMed, Web of Science, and Cochrane Library, to identify studies related to the use of the three CAR-T cell products for treating hematologic malignancies published up to October 5, 2020. We pooled the overall response rate, complete response rate, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome of three products, and then performed subgroup analysis based on the type of product and type of tumor.ResultsThirty-three studies involving 2,172 patients were included in the analysis. All three products showed promising results in patients with different pathological subtypes and clinical characteristics that included those who did not meet the eligibility criteria of licensing trials, with overall response rates of nearly 70% or above and complete response rates of more than 50%. However, high rates of severe immune effector cell-associated neurotoxicity syndrome in patients undergoing axicabtagene ciloleucel treatment and life-threatening cytokine release syndrome in patients with leukemia undergoing tisagenlecleucel treatment required special attention in practice (31%; 95% CI: 0.27–0.35 and 55%; 95% CI: 0.45–0.64, respectively). Moreover, lisocabtagene maraleucel that showed a favorable efficacy and safety in the licensing trial lacked corresponding real-world data.ConclusionBoth axicabtagene ciloleucel and tisagenlecleucel showed considerable efficacy in practice, but need special attention with respect to life-threatening toxicity that can occur in certain situations. Lisocabtagene maraleucel demonstrated excellent efficacy and safety profiles in the licensing trial, but lacked corresponding real-world data. Additional data on the three products are needed in rare histological subtypes to benefit a broader patient population.

BackgroundThe efficacy and safety of chimeric antigen receptor T (CAR-T) cell therapy in the treatment of non-Hodgkin’s lymphoma has already been demonstrated. However, patients with a history of/active secondary central nervous system (CNS) lymphoma were excluded from the licensing trials conducted on two widely used CAR-T cell products, Axicabtagene ciloleucel (Axi-cel) and Tisagenlecleucel (Tisa-cel). Hence, the objective of the present review was to assess whether secondary CNS lymphoma patients would derive a benefit from Axi-cel or Tisa-cel therapy, while maintaining controllable safety.MethodTwo reviewers searched PubMed, Embase, Web of Science, and Cochrane library independently in order to identify all records associated with Axi-cel and Tisa-cel published prior to February 15, 2021. Studies that included secondary CNS lymphoma patients treated with Axi-cel and Tisa-cel and reported or could be inferred efficacy and safety endpoints of secondary CNS lymphoma patients were included. A tool designed specifically to evaluate the risk of bias in case series and reports and the ROBINS-I tool applied for cohort studies were used.ResultsTen studies involving forty-four patients were included. Of these, seven were case reports or series. The other three reports were cohort studies involving twenty-five patients. Current evidence indicates that secondary CNS lymphoma patients could achieve long-term remission following Axi-cel and Tisa-cel treatment. Compared with the non-CNS cohort, however, progression-free survival and overall survival tended to be shorter. This was possibly due to the relatively small size of the CNS cohort. The incidence and grades of adverse effects in secondary CNS lymphoma patients resembled those in the non-CNS cohort. No incidences of CAR-T cell-related deaths were reported. Nevertheless, the small sample size introduced a high risk of bias and prevented the identification of specific patients who could benefit more from CAR-T cell therapy.ConclusionSecondary CNS lymphoma patients could seem to benefit from both Axi-cel and Tisa-cel treatment, with controllable risks. Thus, CAR-T cell therapy has potential as a candidate treatment for lymphoma patients with CNS involvement. Further prospective studies with larger samples and longer follow-up periods are warranted and recommended.

A new kind of beam, i.e., power-exponent helico-conical (PEHC) optical beams, has been proposed in this paper. The proposed beams possess a variety of interesting properties different from optical vortex beams. The intensities of the proposed optical beams at the focal plane are analyzed theoretically and experimentally. The far field mappings are also theoretically analyzed. The results demonstrate that the proposed beams have the ring-broken openings which can be adjusted by modifying the exponent n. The proposed beams can be useful for the extension applications of helico-conical optical beams, especially for optical trapping, guiding, and sorting.

The beams with phase gradients along the line trajectory, i.e., with the momentum flux transverse to the optical axis were generated with the beam shaping method and applied for optical manipulations in this paper. The phase distributions of the reconstructed beam in the focal plane of the objective and the moving velocity of the trapped microparticles were experimentally investigated. The experimental results showed that the moving velocity of the trapped microparticles is linearly dependent on the phase gradient possessed by the reconstructed beam. Furthermore, a generated curve beam was used to transport microparticles quickly and automatically along the curved route to avoid an obstacle. The generation method of the beams with phase gradients is simple. The beams would have potential applications in the fields such as optical trapping and optical sorting.

A new kind of optical element, i.e., composite spiral zone plate (CSZP), is proposed to generate a twin-vortex beam along the optic axis in this paper. The axial diffraction property of the CSZP is analyzed theoretically and experimentally. The results demonstrate that the CSZP can possess two focused vortices with the same intensity peak, different topological charges, and customized axial positions. The proposed optical device exhibits significant potential for various applications including three-dimensional optical manipulation.

A controllable multi-sector array beam is proposed in this Letter. The beam can be generated with the metalens phase. The intensity distribution of the beam at the focal plane is analyzed in detail. The influence of the parameters a and l on the focal field distribution is discussed. The theoretical and experimental results demonstrate that the parameter a affects the size of the beam, and the additional factor l can adjust the sub-region number of the multi-sector array beams. The beam shows potential for use in optical manipulation and image transmission.

Aims Accumulating evidence indicates that serum- and glucocorticoid-inducible kinase 1 (SGK1) plays a role in the development of metabolic syndrome via a poorly understood mechanism. This study aimed to investigate the direct effect of SGK1 on insulin sensitivity in adipose tissue. Materials and methods We ectopically expressed or silenced SGK1 in adipocytes via lentiviral transfection, measured glucose uptake, and evaluated insulin signaling using western blotting. In vivo insulin resistance was measured at the whole-body and adipose tissue levels in db/db mice treated with an inhibitor of SGK1. Results After 8 weeks of SGK1 inhibitor treatment, the serum insulin level and homeostasis model assessment of insulin resistance (HOMA-IR) index were significantly decreased, and AKT phosphorylation in adipose tissue was enhanced in db/db mice. Overexpression of constitutively active SGK1 in adipocytes in vitro decreased AKT phosphorylation and insulin-stimulated glucose uptake. Dexamethasone and oleic acid increased SGK1 expression and decreased AKT phosphorylation and insulin receptor substrate expression in adipocytes. Administration of an inhibitor of SGK1 or Lv-shSGK1 reversed the suppression of insulin signaling induced by dexamethasone and oleic acid. SGK1 overexpression increased FoxO1 phosphorylation, and administration of Lv-shSGK1 reversed an increase in FoxO1 phosphorylation induced by dexamethasone and oleic acid. Conclusions Thus, SGK1 mediates the effect of glucocorticoids and high-fat feeding and induces insulin resistance in adipocytes. Our data suggest that SGK1 is a possible therapeutic target for metabolic syndrome and related complications. This article is protected by copyright. All rights reserved.

Adalimumab, as a TNF inhibitor biologic for the treatment of rheumatoid arthritis, is one of the top-selling drugs worldwide. As its various patents have gradually expired, experiments on its biosimilars are constantly being implemented. In this review, we summarized clinical trials of seven biosimilars currently approved by the FDA and/or EMA for the treatment of rheumatoid arthritis, namely: ABP 501 (Amjevita/Amgevita/Solymbic), BI 695501 (Cyltezo), SB5 (Imraldi/Hadlima), GP2017 (Hyrimoz/Hefiya/Halimatoz), MSB11022 (Idacio), FKB327 (Hulio), and PF-06410293 (Abrilada). Overall, these biosimilars showed similar efficacy, safety, and immunogenicity to adalimumab. All biosimilar switching trials indicated that switching from adalimumab to a biosimilar does not have a significant impact on efficacy, safety, and immunogenicity.

BackgroundGlucocorticoid is one of the common and important strategies for the treatment of chimeric antigen receptor T (CAR-T) cell therapy-related toxicity. However, there has been a theoretical concern about whether glucocorticoids use can impact the expansion of CAR-T cells and thus impair its efficacy. Hence, we reviewed studies related to the Axicabtagene ciloleucel (Axi-cel), a first-class and widely used CAR-T cell product, to elucidate the association between glucocorticoids administration and efficacy of Axi-cel.MethodWe systematically searched PubMed, Embase, Web of Science, and Cochrane Library to identify studies of Axi-cel that used glucocorticoids as an intervention for the treatment of CAR-T cell-related adverse events and respectively evaluated any efficacy endpoints of intervention and controlled cohorts, published up to February 17, 2020. There were no restrictions on research type and language.ResultsA total of eight studies with 706 patients were identified in the systematic review. Except for one study found that high cumulative dose, prolonged duration and early use of glucocorticoids could shorten progression-free survival and/or overall survival, and another study that found a negative effect of glucocorticoids administration on overall survival in univariate analysis but disappeared in multivariate analysis, none of other studies observed a statistically significant association between glucocorticoids administration and progression-free survival, overall survival, complete response, and overall response rate.ConclusionOur study indicated that the association between glucocorticoids therapy and the efficacy of CAR-T cell may be affected by cumulative dose, duration, and timing. There is currently no robust evidence that glucocorticoids can damage the efficacy of CAR-T cell, but the early use of glucocorticoids should be cautiously recommended.

A modified helical phase is presented in this paper. The generated vortex beams with the modified helical phases are characterized with ring-broken intensity distributions. The transverse intensity patterns of the generated vortex beams at a defined axial position and the focal plane are analyzed, respectively. The results demonstrate that the generated beam has an opening, whose size can be customized with a variable l′. The proposed vortex beams realized optical guiding of microparticles in the transverse planes of the beams. This kind of ring-broken beams will be promising for optical manipulation. Keywords: Helical phase, Optical vortices, Optical manipulation

Phenolic compounds (PCs) exist widely in natural environment and human life, which pose a huge threat to human health due to the toxic effects. Therefore, it is necessary to develop effective, robust, and reliable methods for PCs detection. Electrochemical sensors have been attracted widespread attention in detection due to their simple instruments, high sensitivity, fast response, and good selectivity. In addition, carbon nanomaterials (CNMs) have shown great application potential in electrochemical sensing technology due to their unique electrical, optical, thermal, mechanical and chemical properties. Therefore, in this review, the latest technologies of electrochemical sensors based on CNMs for PCs detection over the past decade (2010–2020) were introduced. The application of CNMs involving graphene and its derivatives, carbon nanotubes, graphitic carbon nitride, carbon dots, carbon nanofibers, carbon nanospheres and mesoporous carbon in electrochemical sensors were summarized. Furthermore, it also included the challenges and prospects of CNMs-based electrochemical sensors for PCs detection.

We study an important recommendation problem with implicit feedback from the perspective of item similarity.We exploit the complementarity of the predefined similarity and the learned similarity via a novel mixed similarity model.We develop a novel recommendation algorithm, i.e., pairwise factored mixed similarity model (P-FMSM), based on the mixed similarity and pairwise preference assumption.We showcase the effectiveness of P-FMSM as compared with several state-of-the-art methods on four public datasets. Implicit feedback such as users examination behaviors have been recognized as a very important source of information in most recommendation scenarios. For recommendation with implicit feedback, a good similarity measurement and a proper preference assumption are critical for the quality of personalization services. So far, the similarities used in the state-of-the-art recommendation methods include the predefined similarity and the learned similarity; and the preference assumptions include the well-known pairwise assumption.In this paper, we exploit the complementarity of the predefined similarity and the learned similarity via a novel mixed similarity model. Furthermore, we develop a novel recommendation algorithm, i.e., pairwise factored mixed similarity model (P-FMSM), based on the mixed similarity and pairwise preference assumption. Our P-FMSM is able to (i) capture the locality of the user-item interactions via the symmetric predefined similarity, (ii) model the global correlations among items via the asymmetric learned similarity, and (iii) digest the uncertain implicit feedback via the pairwise preference assumption. Empirical studies on four public datasets show that our P-FMSM can recommend significantly more accurate than several state-of-the-art methods.

Objective The aim of this study was to examine the clinical characteristics and metabolic features of subclinical Cushing’s syndrome (SCS), and to investigate the association of the cortisol level with the metabolic features in patients with SCS. Methods 52 patients with non-functioning adenoma (NFA), 45 patients diagnosed with SCS and 61 patients with overt adrenal Cushing’s syndrome (CS) participated in this study. Clinical data and endocrine function of the patients as well as histological findings were all reviewed. Results 1) The average age of patients with SCS was 52.56±13.25 years, 68.9% patients were female. No difference was detected in age, gender and BMI between patients with SCS and NFA (P > 0.05). Compared to patients with SCS, CS was more common in younger and female patients (43.90±13.83, 83.6%). The prevalence of diabetes mellitus, hypertension, and osteopenia/osteoporosis were significantly higher in patients with SCS compared to those with nonfunctioning tumors (57.8% vs 32.7%, 73.3% vs 53.8%, 41.2% vs 19.2%; P < 0.05). No difference was detected between SCS and CS patients in the prevalence of metabolic disease. 2) Compared to patients with NFA, plasma ACTH level is lower in patients with SCS (P < 0.05). Whereas, the midnight cortisol level and cortisol level after 1mg overnight dexamethasone suppression is higher in SCS than NFA (P < 0.05). No difference was detected between SCS and NFA in 24h urinary free cortisol and early-morning cortisol level (P > 0.05). Compared to SCS, the derangement of ACTH-cortisol axis is more prominent in CS patients demonstrated as suppressed plasma ACTH level and elevated plasma and 24h urine cortisol level. 3) In SCS cohort, SBP, FBG and HbA1c correlated positively with 24h urinary free cortisol (r =0.394, P =0.021; r =0.426, P =0.011, r =0.398, P =0.015; respectively). When controlling for age and gender, the correlation was also significant (P < 0.05). No correlations were found between BMI, TG, HDL and 24h urinary free cortisol. Conclusion Patients with SCS showed slight derangement of the circadian rhythm of cortisol and cortisol excess, and increased prevalence of metabolic disease. Furthermore, the cortisol level was related closely to blood glucose and blood pressure. Our findings might suggestive in therapeutic decision making (conservative vs surgery approach) in patients with SCS.

Objective: Patients with active acromegaly display a range of abnormalities in glucose metabolism and increased bone turnover. Lipocalin 2 (Lcn2) is newly identified as a bone-derived hormone with metabolic regulatory effects. To elucidate interactions between bone and energy homeostasis in active acromegaly patients, we sought to determine whether these patients were characterized by alterations in circulating levels of Lcn2, and potential interactions with body composition and glucose metabolism. Methods: Bone-derived hormone Lcn2 (by ELISA), osteocalcin (by immunoanalysis), body composition (by dual-energy x-ray absorptiometry), and glucose metabolism [homeostasis model assessment, early-phase insulin release (InsAUC30/GluAUC30) and InsAUC120/GluAUC120] were evaluated in 54 acromegalic patients (21 males and 33 females) and in 31 age-, gender-, and body mass index-matched healthy controls (14 males and 17 females). Acromegalic patients were classified as low- or high-Lcn2 group according to the median of Lcn2 level. Results: 1) Acromegalic patients had lower Lcn2 (32.25±11.77 ng/ml vs 58.38±29.66 ng/ml, P < 0.01), higher bone formation markers (osteocalcin and total P1NP, P < 0.05 and P < 0.01, respectively), and higher bone resorption markers (β-Crosslaps, P < 0.001) than controls. After pituitary surgery, serum levels of Lcn2 increased significantly (42.40±16.20 ng/ml vs 33.39±13.45 ng/ml,P

Objectives: The aim of this study was to evaluate the change of bone metabolism and bone remodelling balance in active and biochemical controlled acromegalic patients. Methods: We recruited 68 consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital. Of those, 39 patients after treatments with complete follow-up data were included. 30 sex-, age- and BMI-matched healthy persons were also included as normal controls. Serum calcium, phosphorus, parathyroid hormone (PTH), 25-hydroxy-vitamin D, bone turnover markers [osteocalcin, C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and bone remodelling index were investigated at baseline and after treatment. Univariate and multivariate linear regression analysis was used to determine the independent predictors of bone turnover markers. Results: At baseline, acromegalic patients had higher serum calcium, phosphorus and lower PTH levels than controls (all P < 0.01). Acromegalic patients had higher serum osteocalcin [45.98(31.98, 60.27) vs 15.83(12.74, 19.96) ng/ml, P < 0.01], P1NP [115.50(72.64, 145.90) vs 36.45(30.45, 44.28) ng/ml, P < 0.01] and CTX than controls [1.12(0.79, 1.56) vs 0.37(0.30, 0.50) ng/ml, P < 0.01], and the bone remodelling index of acromegaly patients is significantly increase compared to healthy controls [4.27(1.31, 5.99) vs 0.03(-0.38, 0.63), P < 0.01]. Multivariate linear regression analysis revealed that serum insulin-like growth factor 1 (IGF-1) was an independent predictor for osteocalcin (r = 0.610, P = 0.000), P1NP (r = 0.601, P = 0.000) and CTX (r = 0.596, P = 0.000). After treatment, serum calcium and phosphorus decreased, while PTH increased in acromegalic patients. Serum levels of bone turnover markers osteocalcin, PINP, CTX and bone remodelling index were also significantly decreased after treatment (all P < 0.05). In patients with biochemical control after treatment, bone turnover markers and bone remodelling index almost decreased to normal level (all P > 0.05). Conclusion: Acromegalic patients exhibited PTH-independent calcium-phosphate alterations, enhanced bone turnover state and positive bone remodeling balance. The abnormal bone metabolism is reversible after biochemical control of acromegaly. [Key words]Acromegaly; Bone turnover markers; Bone remodelling index; Growth hormone; Insulin-like growth factor 1