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Purpose: To simulate the advantages of anatomical resection, a new strategy of anatomical thermal ablation was proposed. The objective of this study was to evaluate the clinical value of anatomical thermal ablation (ATA) to treat subcapsular hepatocellular carcinoma by comparing it with anatomical resection (AR) and non-anatomical resection (NAR). Methods: This retrospective cohort study enrolled hepatocellular carcinoma patients with subcapsular tumor diameter ≤ 50 mm treated by ATA or surgical resection at our center from October 2015 to December 2018. ATA features ablation of the Glisson capsule, ablation of the liver parenchyma between the tumor and hepatic veins or inferior vena cava and then puncture from the surrounding part to the central part of the tumor. Outcome parameters were compared. Results: Seventy-six patients were grouped into ATA group, 95 patients into AR group and 41 patients into NAR group. The 1-, 2-, and 3-year local recurrence rates were 0.0%, 0.0%, 0.0% for ATA group, 0.0%, 1.4%, 1.4% for the AR group and 0.0%, 0.0%, and 0.0% for the NAR group, respectively (P = 0.449). The 1-, 2-, and 3-year progression-free survival rates were 90.6%, 80.9%, and 74.6% for ATA group, 91.5%, 80.2%, and 80.2% for the AR group and 82.9%, 73.8%, and 73.8% for the NAR group, respectively (P = 0.608). The 1-, 2-, and 3-year overall survival rates were 100.0%, 95.2%, and 95.2% for the ATA group, 96.8%, 95.6%, and 95.6% for the AR group and 97.6%, 95.0%, and 95.0% for the NAR group, respectively (P = 0.970). No difference was found in major complication rate among these groups (P = 0.091). Conclusion: For subcapsular hepatocellular carcinoma, ATA could be an alternative to surgical resection with its comparable treatment effect and safety. [ABSTRACT FROM AUTHOR]

Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry. The selective reduction of α, β-unsaturated carbonyls remains a challenge. Here the authors report a zinc-based catalyst for this reaction, converting α, β-unsaturated carbonyl compounds into unsaturated alcohols followed by hydrodeoxygenation to form alkenes. [ABSTRACT FROM AUTHOR]

Purpose: The automatic segmentation and detection of prostate cancer (PC) lesions throughout the body are extremely challenging due to the lesions' complexity and variability in appearance, shape, and location. In this study, we investigated the performance of a three-dimensional (3D) convolutional neural network (CNN) to automatically characterize metastatic lesions throughout the body in a dataset of PC patients with recurrence after radical prostatectomy. Methods: We retrospectively collected [68 Ga]Ga-PSMA-11 PET/CT images from 116 patients with metastatic PC at two centers: center 1 provided the data for fivefold cross validation (n = 78) and internal testing (n = 19), and center 2 provided the data for external testing (n = 19). PET and CT data were jointly input into a 3D U-Net to achieve whole-body segmentation and detection of PC lesions. The performance in both the segmentation and the detection of lesions throughout the body was evaluated using established metrics, including the Dice similarity coefficient (DSC) for segmentation and the recall, precision, and F1-score for detection. The correlation and consistency between tumor burdens (PSMA-TV and TL-PSMA) calculated from automatic segmentation and artificial ground truth were assessed by linear regression and Bland‒Altman plots. Results: On the internal test set, the DSC, precision, recall, and F1-score values were 0.631, 0.961, 0.721, and 0.824, respectively. On the external test set, the corresponding values were 0.596, 0.888, 0.792, and 0.837, respectively. Our approach outperformed previous studies in segmenting and detecting metastatic lesions throughout the body. Tumor burden indicators derived from deep learning and ground truth showed strong correlation (R2 ≥ 0.991, all P < 0.05) and consistency. Conclusion: Our 3D CNN accurately characterizes whole-body tumors in relapsed PC patients; its results are highly consistent with those of manual contouring. This automatic method is expected to improve work efficiency and to aid in the assessment of tumor burden. [ABSTRACT FROM AUTHOR]

Background: To systematically evaluate the diagnostic efficacy of urinary Dickkopf-Related Protein 3 (DKK-3) in acute kidney injury and to explore the clinical application value of urinary DKK-3. Method: English databases (PubMed, Embase, Cochrane, and WOS) and Chinese databases (VIP, WanFang data, and China National Knowledge Internet) were screened for relevant papers published before March 12, 2023. After literature screening and data extraction, quality assessment was performed according to the QUADAS-2 scoring system. Then, the combined diagnostic and predictive parameters were calculated using a bivariate mixed effect meta-analysis model. Deek's funnel plot asymmetry test assessed publication bias, and Fagan's nomogram plot was used to verify its clinical utility. Result: A total of 5 studies involving 2787 patients were included in this meta-analysis, of which 4 focused on contrast-induced acute kidney injury (CI-AKI) and 1 focused on AKI associated with cardiac surgery. The analysis showed that urine Dickkopf-3 has high diagnostic accuracy for AKI, with a sensitivity of 0.55 (95% CI [0.41, 0.68]), specificity of 0.80 (95% CI [0.70, 0.87]), positive likelihood ratio (PLR) of 2.7 [1.8, 4.1], negative likelihood ratio (NLR) of 0.56 [0.42, 0.75], diagnostic odds ratio (DOR) of 5 [3, 9], and AUC of 0.74 [0.70–0.77]. We did not perform subgroup analyses for predictive value due to the small number of included studies. Conclusion: Urinary DKK3 may have limited predictive ability for acute kidney injury, especially for AKI associated with cardiac surgery. Therefore, urinary DKK3 may serve as a potential predictor for AKI. However, clinical studies with larger samples are still needed for validation. [ABSTRACT FROM AUTHOR]

Controversial evidence exists on the relationship between body mass index (BMI) and suicide attempts (SA) in patients with major depressive disorder (MDD). This cross-sectional study aimed to explore the association between BMI and SA in first-episode drug-naïve (FEDN) MDD patients in China. The study was conducted from 2016 to 2018 in Taiyuan, China. Univariate and multivariate logistic regression analyzed the BMI–SA association, with subgroup analysis for gender. Threshold effects were examined using two-piecewise regression. In males, BMI was significantly associated with SA (OR = 0.84, 95% CI 0.74–0.94, P = 0.003) after full adjustment, but not in females (OR = 0.97, 95% CI 0.89–1.06, P = 0.541). The interaction with gender was significant (P for interaction < 0.05). Smoothing plots revealed an L-shaped BMI–SA relationship in both genders, with BMI inflection points at 27.3 kg/m2 in males and 21.4 kg/m2 in females. Below the inflection points, BMI is negatively associated with SA in males (OR = 0.75, 95% CI 0.66–0.86, P < 0.001) and females (OR = 0.48, 95% CI 0.32–0.72, P < 0.001). Above the inflection points, no association existed for both genders (all P > 0.05). Results showed an L-shaped nonlinear BMI–SA relationship in FEDN MDD patients but differing BMI inflection points between genders, thus contributing to effective prevention programs for suicide. [ABSTRACT FROM AUTHOR]

Subgrade filling materials affect the settlement in expressway widening projects with a soft soil foundation. On-site monitoring and finite element simulation are used to analyze and compare the settlement and lateral displacement of a lime soil subgrade and mixed gravel and lime soil subgrade. The results show that the trends of the foundation surface settlement, the lateral displacement of the new subgrade foundation at the slope foot, and the newly widened subgrade layered settlement are the same for the two subgrade types. However, the settlement and lateral displacement values are larger for the mixed gravel and lime soil subgrade than for the lime soil subgrade. Moreover, the foundation surface settlement difference between the two subgrade types increases with the distance from the slope foot of the new subgrade. The lateral displacement difference changes during the post-construction period with the depth from the foundation surface and operation time, and the subgrade layered settlement difference changes with the subgrade's longitudinal depth and lateral position. The research results provide information on the subgrade settlement during expressway widening projects. [ABSTRACT FROM AUTHOR]

This study aimed to explore sex differences in the relationship between thyroid function indicators and suicide attempts in first-episode and drug-naïve young major depressive disorder (MDD) patients with comorbid anxiety (MDA). A total of 917 MDD patients (aged 18–35 years) were recruited. The Hamilton depression rating scale (HAMD-17), Hamilton anxiety rating scale (HAMA), positive and negative syndrome scale (PANSS) positive subscale and clinical global impression of severity scale (CGI-S) were used. 467 patients were classified as MDA. The prevalence of suicide attempts was 31.3% in MDA patients, which was significantly higher than that (7.3%) in MDD patients without anxiety. Compared with MDA patients without suicide attempts, MDA patients with suicide attempts were older, had a later age of onset, higher HAMD-17, HAMA, and PANSS positive symptom subscale scores, as well as higher TSH, TgAb and TPOAb levels. For male patients, TSH and TPOAb levels were independently associated with suicide attempts. For female patients, HAMA, PANSS positive symptom scores, CGI-S score and TPOAb levels were independently associated with suicide attempts. Our results suggest that the indicators of thyroid function which can predict suicide attempts in male and female MDA patients have sex differences. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of surgical procedures (transoral laser microsurgery (TLM) and open partial laryngectomy (OPL)) on the prognosis of patients with early laryngeal cancer. Methods: A total of 760 patients diagnosed with early laryngeal cancer (T1-2N0M0) and treated with TLM (n = 416) or OPL (n = 344) between 2004 and 2015 were abstracted from the SEER database. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (SIPTW) were performed to obtain comparable cohorts. The survival rates were estimated by the Kaplan–Meier method, and compared using the log-rank test. Univariate and multivariate Cox regression analyses with a false discovery rate (FDR) correction were applied to contrast the association between two surgical approaches and overall survival (OS) and disease-specific survival (DSS). Results: The 5-year OS for the TLM group was 79.5% versus 77.7% for the OPL group (P = 0.619). Similar results were revealed for the comparison of 5-year DSS rates (91.1% versus 91.5%, P = 0.891). After PSM and SIPTW balance the confounding factors, no significant difference was observed in the OS and DSS of patients treated with TLM compared to patients treated with OPL. The consistent results were still yielded (all P > 0.05), when stratified by gender, age, year of diagnosis, residence, household income, tumor site, T stage, differentiation, and adjuvant therapy. Conclusion: This study provides strong evidence that there is no significant difference in the prognosis of early laryngeal carcinoma between the treatment of TLM and OPL, which may be helpful to guide the clinical decision-making of these patients. [ABSTRACT FROM AUTHOR]

Dolomite genesis is a century-old mystery in sedimentology. To reveal the mechanism of dolomite genesis, two core problems need to be addressed. The first is the origin and migration mechanism of Mg2+-rich fluids during the dolomitization process. The second is the kinetic barrier caused by Mg2+ hydration during dolomite precipitation at low temperatures. To address these problems, our study, based on detailed petrological, sedimentological, geochemical (major and trace elements), and isotopic (C-O-Mg) analysis, clarified the source and migration of Mg2+-rich fluids and the kinetic barrier mechanism of low-temperature dolomite precipitation in the Upper Sinian Qigebulake Formation and the Lower Cambrian Xiaoerbulake Formation in the Tarim Basin. First, we found that the Mg2+-rich fluids required for the dolomitization of dolomite in the Xiaoerbulake Formation were primarily derived from the Early Cambrian marine fluid. At the interface of the sedimentary cycle, δ26Mg values fluctuated considerably, indicating that the sequence interface was the starting point and channel for the migration of dolomitized fluids. Sea level variation plays a major role in controlling the dolomitization process of the Xiaoerbulake Formation. Second, the Qigebulake Formation contains low-temperature dolomite with Mg2+-rich fluids supplied by seawater, microorganisms, and sedimentary organic matter. Comprehensive analysis shows that the dolomite of the Qigebulake Formation was formed by microbial induction by anaerobic methane bacteria. Finally, the properties and sources of dolomitization fluids and the formation process of dolomite were the reasons for the difference in the Mg isotope composition of dolomite during the Sinian-Cambrian transition. This study reveals the genetic mechanism of the Sinian-Cambrian dolomite in the Tarim Basin and establishes a new method to explain the genesis of microbial dolomite by C-O-Mg isotopes, providing a reference for the reconstruction of the formation and evolution of dolomites. [ABSTRACT FROM AUTHOR]

Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies1–7. However, CAR-T cell therapy currently has several limitations8–12. Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR–Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell non-Hodgkin lymphoma (ClinicalTrials.gov, ), we observed a high rate (87.5%) of complete remission and durable responses without serious adverse events in eight patients. Notably, these enhanced CAR-T cells were effective even at a low infusion dose and with a low percentage of CAR+ cells. Single-cell analysis showed that the electroporation method resulted in a high percentage of memory T cells in infusion products, and PD1 interference enhanced anti-tumour immune functions, further validating the advantages of non-viral, PD1-integrated CAR-T cells. Collectively, our results demonstrate the high safety and efficacy of non-viral, gene-specific integrated CAR-T cells, thus providing an innovative technology for CAR-T cell therapy.Non-viral CAR-T cells with gene-specific targeted integration are safe and effective in patients with lymphoma. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infected about 296 million people worldwidely, while clinical useful therapeutic agents were still limited. Capsid assembly modulators (CAM) have been validated as efficient anti-HBV virus agents with the potential to achieve functional cure, therefore piqued much attention in recent years. There are various novel scaffold agents been developed and more than ten CAM candidates have been progressed into clinical trials with efficient anti-HBV activities. Herein, we summarised the SAR-based development of CAMs with various scaffolds, including heteroaryldihydropyrimidines (HAPs), phenylacrylamides (PPAs), sulfamoylbenzamides (SBAs), pyridazinone, bis-heterocycle, arylformamides, aminothiazoles, and others, which may provide new suggestions for the further development of CAMs. [ABSTRACT FROM AUTHOR]

Utilizing a decade-long observation from the spaceborne dual-frequency precipitation radar, this study investigates the seasonal variations and microphysical characteristics of precipitation in North China. The results elucidate that the mean storm top height (STH) attains its zenith during the summer, potentially linked to the pronounced strong evaporation and convection. An upsurge in STH is frequently correlated with the evolution of precipitation particles of greater dimensions for both convective and stratiform precipitation. This investigation further discerns that the predominant microphysical mechanisms underlying precipitation during the process from altitudes of 3 km to 1 km exhibit significant seasonal variations and are contingent upon the precipitation types. Collision and coalescence processes are identified as the predominant contributors to precipitation formation, whereas evaporative processes and particle size sorting are less significant. For the coalescence process, the lowest is from summer (29.24%) to autumn (38.01%), spring (50.84%) and winter (58.43%). Additionally, this study observes that the altitude of the melting layer in North China(3–4 km) is relatively lower than that in East China and Yangtze-Huai River Valley region(4.5 km), which may be ascribed to the higher latitude, resulting in comparatively lower temperatures aloft and thus a reduced height for the melting layer. [ABSTRACT FROM AUTHOR]

The closure temperature refers to the temperature at which a structure forms an overall constrained structural system, also called the initial temperature. A reasonable closure temperature can avoid large additional stresses caused by excessive air temperature changes in large-span structures. To study the thermal action of the closure temperature on a structure, a probability distribution function of uniform temperature action is proposed. The effect of closure temperature is studied by introducing an adjustment coefficient. The partial factor and combination value coefficient of thermal action are presented, and their reliabilities are verified by the first-order second-moment method. The results show that with increasing adjustment coefficient, the probability distribution of thermal action tends to be uniformly divergent, the partial factor of thermal action increases, and the combination value coefficient decreases. The optimal closure temperature times are in March, April, October, and November for six cities in China. In this case, an adjustment coefficient of 0.3, a partial factor of 1.5, and the combination value coefficient of 0.45 are recommended. In addition, the partial factor of 1.5 and the combination value coefficient of 0.45 can be verified by reliability verification, which is more economical and reasonable with regard to ensuring safety. [ABSTRACT FROM AUTHOR]

Designing heterogeneous solid surface frustrated Lewis pair (ssFLP) catalyst for hydrogenation is a new challenge in catalysis and no research has been reported on the construction of ssFLP on boehmite (AlOOH) surfaces up to now as far as we know. Herein, AlOOH with a layer structure is prepared and it is found that the Lewis basic OHv site (one H removed from OH) and an adjacent Lewis acidic unsaturated Al site (Al3+unsatur.) proximal to a surface OHv (OH vacancy) on AlOOH layers could form the ssFLP. The layered structure of AlOOH and its abundant OH defects over the surface result in a high concentration of OHv/Al3+unsatur. FLPs, which are conducive to highly efficient hydrogen activation for hydrogenation of olefins and alkynes with low H-H bond dissociates activation energy of 0.16 eV under mild conditions (T = 80°C and P(H2) = 2.0 MPa). This work develops a new kind of hydrogenation catalyst and provides a new perspective for creating solid surface FLP. Designing heterogeneous solid surface frustrated Lewis pair (ssFLP) catalyst for hydrogenation is a new challenge in catalysis. Here, the authors show the ssFLP can be constructed on layered AlOOH for hydrogenation reactions under mild conditions. [ABSTRACT FROM AUTHOR]

With the advent of information era, the issues on video copyright continue to emerge. In the grey industrial chain of piracy, the film industry is suffering a major disaster area. The current protection schemes for video copyright are inefficient and costly so that video industry still has to face the infringement. To address poor robustness, weak imperceptibility and difficulty in traceability of the current protection schemes for video copyright, this paper proposes a novel zero-watermarking scheme based on NSCT-SVD and blockchain for video copyright. In addition, we research the feasibility and reason of combining zero-watermarking with blockchain. The designed zero-watermarking algorithm is based on NSCT-SVD, Arnold Transform and key-frames extraction algorithm which is based on distance threshold clustering. The results show the extracted features from video are stable and secure than DWT-SVD based and the past non-blocking. The performance of the blockchain scheme designed for video copyright practices well. Comparatively, the discussion and results showed that the proposed scheme has been verified more credible and efficient in authoritative traceability compared to trusted third party based. The registration information cannot be tampered and be more suitable for copyright protection. [ABSTRACT FROM AUTHOR]

Although base editors are useful tools for precise genome editing, current base editors can only convert either adenines or cytosines. We developed a dual adenine and cytosine base editor (A&C-BEmax) by fusing both deaminases with a Cas9 nickase to achieve C-to-T and A-to-G conversions at the same target site. Compared to single base editors, A&C-BEmax's activity on adenines is slightly reduced, whereas activity on cytosines is higher and RNA off-target activity is substantially decreased. Base editors that modify both adenine and cytosine broaden the potential applications of base editing. [ABSTRACT FROM AUTHOR]

Base editor technology, which uses CRISPR–Cas9 to direct cytidine deaminase enzymatic activity to specific genomic loci, enables the highly efficient introduction of precise cytidine-to-thymidine DNA alterations. However, existing base editors create unwanted C-to-T alterations when more than one C is present in the enzyme's five-base-pair editing window. Here we describe a strategy for reducing bystander mutations using an engineered human APOBEC3A (eA3A) domain, which preferentially deaminates cytidines in specific motifs according to a TCR>TCY>VCN hierarchy. In direct comparisons with the widely used base editor 3 (BE3) fusion in human cells, our eA3A-BE3 fusion exhibits similar activities on cytidines in TC motifs but greatly reduced editing on cytidines in other sequence contexts. eA3A-BE3 corrects a human β-thalassemia promoter mutation with much higher (>40-fold) precision than BE3. We also demonstrate that eA3A-BE3 shows reduced mutation frequencies on known off-target sites of BE3, even when targeting promiscuous homopolymeric sites. [ABSTRACT FROM AUTHOR]

We previously reported that loss of Nrdp1 contributes to human glioma progression by reducing apoptosis. However, the role of Nrdp1 in glioma migration and invasion has not been investigated. Here, we report that ErbB3, a substrate of Nrdp1, is undetectable in normal brain tissues and grade II/III glioma tissues, but is abundant in a certain percentage of grade IV glioma tissues and is associated with the loss of Nrdp1. This suggests that Nrdp1 may be involved in glioma migration and invasion by regulating ErbB3. Thus, the role of Nrdp1/ErbB3 signaling in glioma cell migration and invasion was investigated using Nrdp1 loss- and gain-of-function. The results show that down-regulation of Nrdp1 by use of short hairpin RNA promoted glioma cell migration and invasion. In contrast, overexpression of Nrdp1 significantly inhibited glioma cell migration and invasion. Further investigation on molecular targets revealed that Nrdp1 decreased the level of ErbB3, which resulted in decreasing p-AKT thereby reducing cytoplasmic p27. Taken together, these findings suggest that Nrdp1-mediated ErbB3 degradation suppresses glioma migration and invasion and that loss of Nrdp1 may amplify ErbB3 signaling to contribute to glioma migration and invasion. These findings suggest that Nrdp1 may be a target for glioma therapy. [ABSTRACT FROM AUTHOR]

Spermatogonial stem cells (SSCs) can produce numerous male gametes after transplantation into recipient testes, presenting a valuable approach for gene therapy and continuous production of gene-modified animals. However, successful genetic manipulation of SSCs has been limited, partially due to complexity and low efficiency of currently available genetic editing techniques. Here, we show that efficient genetic modifications can be introduced into SSCs using the CRISPR-Cas9 system. We used the CRISPR-Cas9 system to mutate an EGFP transgene or the endogenous Crygc gene in SCCs. The mutated SSCs underwent spermatogenesis after transplantation into the seminiferous tubules of infertile mouse testes. Round spermatids were generated and, after injection into mature oocytes, supported the production of heterozygous offspring displaying the corresponding mutant phenotypes. Furthermore, a disease-causing mutation in Crygc (Crygc−/−) that pre-existed in SSCs could be readily repaired by CRISPR-Cas9-induced nonhomologous end joining (NHEJ) or homology-directed repair (HDR), resulting in SSC lines carrying the corrected gene with no evidence of off-target modifications as shown by whole-genome sequencing. Fertilization using round spermatids generated from these lines gave rise to offspring with the corrected phenotype at an efficiency of 100%. Our results demonstrate efficient gene editing in mouse SSCs by the CRISPR-Cas9 system, and provide the proof of principle of curing a genetic disease via gene correction in SSCs. [ABSTRACT FROM AUTHOR]

This study aims to investigate whether the expression of heat shock protein 90 (HSP90) is associated with the malignant pheochromocytoma (PHEO) and the effects of 17-allylamino-17-demethoxygeldanamcyin (17-AAG) on the expression of vascular endothelial growth factor (VEGF) in PHEO cell line PC12. The expression of HSP90 was investigated in 38 paraffin-embedded samples of PHEO patients using immunohistochemistry. The time and concentration effects of 17-AAG were investigated in PHEO PC12 cells. Cell proliferation was measured by MTT assay and cell counting. Apoptosis was detected by flow cytometry. Positive staining for HSP90 was found in 14 of 17 malignant (82.35 %) and in 5 of 21 (23.81 %) benign PHEOs. There existed a significant statistical difference between the malignant group and the benign ones ( P < 0.001). 17-AAG inhibited the proliferation of HCC cells in a time- and concentration-dependent manner. The apoptosis rates of PC12 cells after treatment with 0.1 μmol/L for 6, 12, 24, and 48 h were significantly higher than that in blank control group. 17-AAG significantly downregulated VEGF-165 protein level in PC12 cells. This study has confirmed that the specific HSP90 inhibitor 17-AAG can play a therapeutic role in malignant PHEO treatment, and HSP90 qualifies as a promising new target in malignant PHEO. [ABSTRACT FROM AUTHOR]

Background: The objective of the present study was twofold: to demonstrate our experience with unilateral adrenalectomy in the treatment of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) caused by bilateral adrenocortical hyperplasias, and to evaluate the long-term results as evidenced by the main laboratory and clinical findings. Methods: From February 2000 to August 2009, unilateral adrenalectomy was performed on 27 patients with ACTH-independent CS and bilateral adrenocortical hyperplasias, including 14 patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH) and 13 patients with primary pigmented nodular adrenocortical disease (PPNAD). Signs and symptoms of CS, endocrine examinations, and radiographic imaging were evaluated preoperatively and postoperatively. Results: At a median follow-up of 69 months (range: 23-120 months) for AIMAH and 47 months (range: 16-113 months) for PPNAD, 25 patients were cured by unilateral adrenalectomy. Serum cortisol level, daily urinary free cortisol (UFC), and plasma ACTH regained the normal range in both AIMAH and PPNAD patients at monthly follow-up visits; the circadian serum cortisol rhythm returned to normal, and a normal responsiveness to overnight low-dose dexamethasone administration (LDDST) became obvious. Both systolic and diastolic blood pressure (BP) levels were significantly reduced: 85 % of patients recovered normal BP levels, and the remaining patients need antihypertensive drugs, but at a reduced dose. No surgery-related morbidity occurred, and there was no sign of further enlargement of the residual adrenal gland after successful unilateral adrenalectomy. One patient with PPNAD and another patient with AIMAH with similar weights and sizes of the bilateral adrenals needed contralateral adrenalectomy. Conclusions: Unilateral adrenalectomy may be the suitable treatment for selected patients with AIMAH and PPNAD. It can achieve long-term remission of CS and improve glycemic control and BP values. [ABSTRACT FROM AUTHOR]