Remodeling and Regenerative Properties of Fully Absorbable Meshes for Abdominal Wall Defect Repair: A Systematic Review and Meta-Analysis of Animal Studies.

Fully absorbable meshes can repair abdominal wall defects and effectively reduce the incidence of complications, but different types of fully absorbable meshes have different remodeling and regeneration effects. In order to investigate and compare the effects of different fully absorbable meshes on remodeling and regeneration in animals and reduce the biological risk of clinical translation, SYRCLE was adopted to evaluate the methodological quality of the included studies, and GRADE and ConQual were used to evaluate the quality of evidence. According to the inclusion and exclusion criteria, a total of 22 studies related to fully absorbable meshes were included in this systematic review. These results showed that fiber-based synthetic materials and fiber-based natural materials exhibited better restorative and regenerative effects indicated by infiltration and neovascularization, when compared with a porcine acellular dermal matrix. In addition, the human acellular dermal matrix was found to have a similar regenerative effect on the host extracellular matrix and scaffold degradation compared to the porcine acellular dermal matrix, porcine intestinal submucosa, and fiber-based natural materials, but it offered higher tensile strength than the other three. The quality of the evidence in this field was found to be poor. The reasons for downgrading were analyzed, and recommendations for future research included more rigor in study design, more transparency in result reporting, more standardization of animal models and follow-up time for better evaluation of the remodeling and regenerative performance of abdominal wall hernia repair meshes, and less biological risk in clinical translation.

Wireless flow-powered miniature robot capable of traversing tubular structures.

Wireless millimeter-scale robots capable of navigating through fluid-flowing tubular structures hold substantial potential for inspection, maintenance, or repair use in nuclear, industrial, and medical applications. However, prevalent reliance on external powering constrains these robots' operational range and applicable environments. Alternatives with onboard powering must trade off size, functionality, and operation duration. Here, we propose a wireless millimeter-scale wheeled robot capable of using environmental flows to power and actuate its long-distance locomotion through complex pipelines. The flow-powering module can convert flow energy into mechanical energy, achieving an impeller speed of up to 9595 revolutions per minute, accompanied by an output power density of 11.7 watts per cubic meter and an efficiency of 33.7%. A miniature gearbox module can further transmit the converted mechanical energy into the robot's locomotion system, allowing the robot to move against water flow at an average rate of up to 1.05 meters per second. The robot's motion status (moving against/with flow or pausing) can be switched using an external magnetic field or an onboard mechanical regulator, contingent on different proposed control designs. In addition, we designed kirigami-based soft wheels for adaptive locomotion. The robot can move against flows of various substances within pipes featuring complex geometries and diverse materials. Solely powered by flow, the robot can transport cylindrical payloads with a diameter of up to 55% of the pipe's diameter and carry devices such as an endoscopic camera for pipeline inspection, a wireless temperature sensor for environmental temperature monitoring, and a leak-stopper shell for infrastructure maintenance.

Undulatory Propulsion at Milliscale on Water Surface.

The oscillatory pitch motion at the leading edge of a millimeter-scale flexible sheet on the water surface can generate undulatory locomotion for swimming, similar to a honeybee vibrating its wings for propulsion. The influence of various parameters on such swimming strategy remains unexplored. This study uses magnetic milliswimmers to probe the propulsion mechanics and impact of different parameters. It is found that this undulatory propulsion is driven by capillary forces and added mass effects related to undulatory waves of the milliswimmers, along with radiation stress stemming from capillary waves at the interface. Modifying the parameters such as actuation frequency, pitch amplitude, bending stiffness, and hydrofoil length alters the body waveform, thus, affecting the propulsion speed and energy efficiency. Although undulatory motion is not a prerequisite for water surface propulsion, optimizing body stiffness to achieve a proper undulatory waveform is crucial for efficient swimming, balancing energy consumption, and speed. The study also reveals that the induced water flow is confined near the water surface, and the flow structures evolve with varying factors. These discoveries advance the understanding of undulatory water surface propulsion and have implications for the optimal design of small-scale swimming soft robots in the future.

Systemically functional characterization of regiospecific flavonoid O-methyltransferases from Glycine max.

Plants produce diverse flavonoids for defense and stress resistance, most of which have health benefits and are widely used as food additives and medicines. Methylation of the free hydroxyl groups of flavonoids, catalyzed by S-adenosyl-l-methionine-dependent O-methyltransferases (OMTs), significantly affects their physicochemical properties and bioactivities. Soybeans (Glycine max) contain a rich pool of O-methylated flavonoids. However, the OMTs responsible for flavonoid methylation in G. max remain largely unknown. We screened the G. max genome and obtained 22 putative OMT-encoding genes that share a broad spectrum of amino acid identities (25-96%); among them, 19 OMTs were successfully cloned and heterologously expressed in Escherichia coli. We used the flavonoids containing the free 3, 5, 7, 8, 3', 4' hydroxyl group, such as flavones (luteolin and 7, 8-dihydroxyflavone), flavonols (kaempferol and quercetin), flavanones (naringenin and eriodictyol), isoflavonoids (daidzein and glycetein), and caffeic acid as substrates, and 15 OMTs were proven to catalyze at least one substrate. The methylation activities of these GmOMTs covered the 3, 7, 8, 3', 4'- hydroxyl of flavonoids and 7, 4'- hydroxyl of isoflavonoids. The systematic characterization of G. max flavonoid OMTs provides insights into the biosynthesis of methylated flavonoids in soybeans and OMT bioparts for the production of methylated flavonoids via synthetic biology.

Causal Relationship Between Sleep Traits and Hypothalamic-Pituitary-Target Gland Axis Function: A Mendelian Randomization Study.

Background: In recent years, multiple observational studies have confirmed the association between sleep traits and various human physiopathological states. However, the causal relationship between sleep traits and hypothalamic-pituitary-target gland axis (HPTGA) function remains unknown. Methods: We obtained summary statistics on sleep traits (insomnia, chronotype, and sleep duration (long and short)) from the UK Biobank database. Data related to the HPTGA functions were obtained from the publicly available database. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between different sleep traits and the HPTGA function. Reverse MR analysis was conducted to examine the direction of causality. Results: The MR analysis results suggested that chronotype is associated with decreased levels of six hormones in HPTGA. Sleep duration was causally associated with decreased levels of free thyroxine and progesterone. Both long and short sleep durations are detrimental to the secretion of prolactin-releasing peptide, somatostatin, and plasma cortisol, while short sleep duration can promote progesterone secretion. After gender stratification, we found that female reproductive function is more susceptible to the influence of unfavorable sleep traits. Conclusion: Our MR analysis indicated a significant causal association between chronotype and suppressed gonadal function in healthy adult humans, with no apparent gender-specific effect. Extreme sleep durations were also found to be detrimental to the maintenance of normal HPTGA secretion function. Compared to males, gonadal function in the female cohort is more susceptible to extreme sleep habits. Subsequent observational studies are urgently needed to confirm the underlying mechanisms.

Design and build of small-scale magnetic soft-bodied robots with multimodal locomotion.

Small-scale magnetic soft-bodied robots can be designed to operate based on different locomotion modes to navigate and function inside unstructured, confined and varying environments. These soft millirobots may be useful for medical applications where the robots are tasked with moving inside the human body. Here we cover the entire process of developing small-scale magnetic soft-bodied millirobots with multimodal locomotion capability, including robot design, material preparation, robot fabrication, locomotion control and locomotion optimization. We describe in detail the design, fabrication and control of a sheet-shaped soft millirobot with 12 different locomotion modes for traversing different terrains, an ephyra jellyfish-inspired soft millirobot that can manipulate objects in liquids through various swimming modes, a larval zebrafish-inspired soft millirobot that can adjust its body stiffness for efficient propulsion in different swimming speeds and a dual stimuli-responsive sheet-shaped soft millirobot that can switch its locomotion modes automatically by responding to changes in the environmental temperature. The procedure is aimed at users with basic expertise in soft robot development. The procedure requires from a few days to several weeks to complete, depending on the degree of characterization required.

The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

Cholesteric Liquid Crystal Polymeric Coatings for Colorful Artificial Muscles and Motile Humidity Sensor Skin Integrated with Magnetic Composites.

Structural colorful cholesterics show impressive susceptibility to external stimulation, leading to applications in electro/mechano-chromic devices. However, out-of-plane actuation of structural colorful actuators based on cholesterics and the integration with other stimulation remains underdeveloped. Herein, colorful actuators and motile humidity sensors are developed using humidity-responsive cholesteric liquid crystal networks (CLCNs) and magnetic composites. The developed colorful actuator can exhibit synergistic out-of-plane shape morphing and color change in response to humidity, with CLCNs as colorful artificial muscles. Through the integration with magnetic control, the motile sensor can be navigated to open and confined spaces with the aid of friction to detect local relative humidity. The integration of multi-stimulation actuation of cholesteric magnetic actuators will expand the research frontier of structural colorful actuators and motile sensors for confined spaces.

Effects of 18 Months of Growth Hormone Replacement Therapy on Bone Mineral Density in Patients with Adult Growth Hormone Deficiency: A Retrospective Study.

Objective: The effect of physiological dose growth hormone (GH) replacement therapy on bone mineral density (BMD) in adults with growth hormone deficiency (GHD) is not well defined. We aimed to investigate the effects of 18 months of treatment with recombinant human growth hormone (rhGH) at physiological doses on BMD, body composition (BC), and quality of life (QoL). Methods: Sixty-eight patients diagnosed with adult growth hormone deficiency (AGHD) in our hospital were included in this retrospective study. All patients received individualized rhGH replacement to maintain normal serum insulin-like growth factor-1 (IGF-1) levels. BMD and BC measurements were performed by dual energy X-ray absorptiometry (DXA). Excluding those with incomplete follow-up data, we analyzed BMD in 68 patients, as well as BC and QoL in 36 of them. Results: Compared with the baseline, lumbar spine BMD decreased by 0.008 g/cm2 (P=0.006) and increased by 0.011 g/cm2 (P=0.045) at month 18, and total hip BMD decreased by 0.005 g/cm2 (P=0.008) and did not change significantly from the baseline at month 18. The changes in BMD did not differ by sex, and the increase in BMD was more pronounced in patients with low Z-scores at the baseline (lumbar spine: P=0.005 and total hip: P=0.018). The percentage change from the baseline in BMD was greater for the lumbar spine than for the total hip (P=0.003). Lean body mass (LBM) increased significantly (P=0.012), total body fat ratio (TBF%) decreased significantly (P=0.011), visceral adipose tissue (VAT) decreased significantly (P=0.016), and QoL improved significantly (P < 0.001). Conclusions: Within 18 months of treatment, bone resorption manifested first, BMD decreased to a nadir at month 6, and then it increased. The increase in BMD was greater in the lumbar spine than in the hip, and the increase was more pronounced in patients with low BMD. Eighteen months of rhGH replacement therapy significantly improved lumbar spine BMD and improved BC and QoL.

Effect of Umbilical Cord Mesenchymal Stem Cell Transplantation Under LIFPUS Pretreatment on Thyroid Function in EAT Rats.

BACKGROUND: A growing number of studies have demonstrated that mesenchymal stem cells (MSCs) can effectively regulate the progression of multiple autoimmune diseases and can respond positively to mechanical stimulation by ultrasound in an in vitro setting to improve transplantation efficacy. OBJECTIVE: The aim of this study was to activate hUC-MSCs by pretreatment with low-intensity focused pulsed ultrasound (LIFPUS) in an in vitro environment and transplant them into a rat model of EAT via tail vein. To investigate the efficacy and potential mechanism of action of hUC-MSCs in the treatment of EAT. METHODS: In this study, 40 female lewis rats were divided into control, EAT, hUC-MSCs treatment and LIFPUS pretreatment transplantation group. EAT models were established by subcutaneous multi-point injection of PTG+Freund's adjuvant, and the primary hUC-MSCs were treated with different gradients of LIFPUS irradiation or sham irradiation in an in vitro environment and screened by Western Blot (WB), flow cytology cycle analysis, and cellular immunofluorescence to find the optimal treatment parameters for LIFPUS to promote cell proliferation. After tail vein injection of different pretreatment groups of hUC-MSCs, Homing sites of hUC-MSCs in vivo, circulating autoantibody expression levels and local thyroid histopathological changes were assessed by enzyme-linked immunosorbent assay (ELISA), spleen index, tissue hematoxylin-eosin (HE) staining and immunohistochemistry. The expression levels of apoptotic proteins Bcl-2, Bax and endoplasmic reticulum stress-related proteins Chop and EIF2α in thyroid tissue were also examined by WB. RESULTS: LIFPUS can effectively stimulate hUC-MSCs in vitro to achieve the most optimal proliferative and secretory activity. In the EAT model, hUC-MSCs can effectively reduce thyroid cell apoptosis, improve thyroid function and reduce excessive accumulation of autoimmune antibodies in the body. in comparison, the LIFPUS pretreatment group showed a more favorable treatment outcome. Further experiments demonstrated that hUC-MSCs transplantation may effectively inhibit the apoptotic state of thyroid follicles and follicular epithelial cells by down-regulating the unfolded protein reaction (UPR) of the PERK pathway, thus providing a therapeutic effect for AIT. CONCLUSION: hUC-MSCs can effectively reverse the physiological function of EAT thyroid tissue and reduce the accumulation of circulating antibodies in the body. in comparison, hUC-MSCs under LIFPUS pretreatment showed more desirable therapeutic potential. hUC-MSCs transplanted under LIFPUS pretreatment may be a new class of safe therapeutic modality for the treatment of AIT.

Deep learning methods may not outperform other machine learning methods on analyzing genomic studies.

Deep Learning (DL) has been broadly applied to solve big data problems in biomedical fields, which is most successful in image processing. Recently, many DL methods have been applied to analyze genomic studies. However, genomic data usually has too small a sample size to fit a complex network. They do not have common structural patterns like images to utilize pre-trained networks or take advantage of convolution layers. The concern of overusing DL methods motivates us to evaluate DL methods' performance versus popular non-deep Machine Learning (ML) methods for analyzing genomic data with a wide range of sample sizes. In this paper, we conduct a benchmark study using the UK Biobank data and its many random subsets with different sample sizes. The original UK Biobank data has about 500k participants. Each patient has comprehensive patient characteristics, disease histories, and genomic information, i.e., the genotypes of millions of Single-Nucleotide Polymorphism (SNPs). We are interested in predicting the risk of three lung diseases: asthma, COPD, and lung cancer. There are 205,238 participants have recorded disease outcomes for these three diseases. Five prediction models are investigated in this benchmark study, including three non-deep machine learning methods (Elastic Net, XGBoost, and SVM) and two deep learning methods (DNN and LSTM). Besides the most popular performance metrics, such as the F1-score, we promote the hit curve, a visual tool to describe the performance of predicting rare events. We discovered that DL methods frequently fail to outperform non-deep ML in analyzing genomic data, even in large datasets with over 200k samples. The experiment results suggest not overusing DL methods in genomic studies, even with biobank-level sample sizes. The performance differences between DL and non-deep ML decrease as the sample size of data increases. This suggests when the sample size of data is significant, further increasing sample sizes leads to more performance gain in DL methods. Hence, DL methods could be better if we analyze genomic data bigger than this study.

Magnetically actuated gearbox for the wireless control of millimeter-scale robots.

The limited force or torque outputs of miniature magnetic actuators constrain the locomotion performances and functionalities of magnetic millimeter-scale robots. Here, we present a magnetically actuated gearbox with a maximum size of 3 millimeters for driving wireless millirobots. The gearbox is assembled using microgears that have reference diameters down to 270 micrometers and are made of aluminum-filled epoxy resins through casting. With a magnetic disk attached to the input shaft, the gearbox can be driven by a rotating external magnetic field, which is not more than 6.8 millitesla, to produce torque of up to 0.182 millinewton meters at 40 hertz. The corresponding torque and power densities are 12.15 micronewton meters per cubic millimeter and 8.93 microwatt per cubic millimeter, respectively. The transmission efficiency of the gearbox in the air is between 25.1 and 29.2% at actuation frequencies ranging from 1 to 40 hertz, and it lowers when the gearbox is actuated in viscous liquids. This miniature gearbox can be accessed wirelessly and integrated with various functional modules to repeatedly generate large actuation forces, strains, and speeds; store energy in elastic components; and lock up mechanical linkages. These characteristics enable us to achieve a peristaltic robot that can crawl on a flat substrate or inside a tube, a jumping robot with a tunable jumping height, a clamping robot that can sample solid objects by grasping, a needle-puncture robot that can take samples from the inside of the target, and a syringe robot that can collect or release liquids.

Soft-robotic ciliated epidermis for reconfigurable coordinated fluid manipulation.

The fluid manipulation capabilities of current artificial cilia are severely handicapped by the inability to reconfigure near-surface flow on various static or dynamically deforming three-dimensional (3D) substrates. To overcome this challenge, we propose an electrically driven soft-robotic ciliated epidermis with multiple independently controlled polypyrrole bending actuators. The beating kinematics and the coordination of multiple actuators can be dynamically reconfigured to control the strength and direction of fluid transportation. We achieve fluid transportation along and perpendicular to the beating directions of the actuator arrays, and toward or away from the substrate. The ciliated epidermises are bendable and stretchable and can be deployed on various static or dynamically deforming 3D surfaces. They enable previously difficult to obtain fluid manipulation functionalities, such as transporting fluid in tubular structures or enhancing fluid transportation near dynamically bending and expanding surfaces.

On-demand anchoring of wireless soft miniature robots on soft surfaces.

Untethered soft miniature robots capable of accessing hard-to-reach regions can enable new, disruptive, and minimally invasive medical procedures. However, once the control input is removed, these robots easily move from their target location because of the dynamic motion of body tissues or fluids, thereby restricting their use in many long-term medical applications. To overcome this, we propose a wireless spring-preloaded barbed needle release mechanism, which can provide up to 1.6 N of force to drive a barbed needle into soft tissues to allow robust on-demand anchoring on three-dimensional (3D) surfaces. The mechanism is wirelessly triggered using radio-frequency remote heating and can be easily integrated into existing untethered soft robotic platforms without sacrificing their mobility. Design guidelines aimed at maximizing anchoring over the range of the most biological tissues (kPa range) and extending the operating depth of the device inside the body (up to 75%) are also presented. Enabled by these advances, we achieve robust anchoring on a variety of ex vivo tissues and demonstrate the usage of such a device when integrated with existing soft robotic platforms and medical imaging. Moreover, by simply changing the needle, we demonstrate additional functionalities such as controlled detachment and subsurface drug delivery into 3D cancer spheroids. Given these capabilities, our proposed mechanism could enable the development of a new class of biomedical-related functionalities, such as local drug delivery, disease monitoring, and hyperthermia for future untethered soft medical robots.

Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells.

Palytoxin (PLTX) is a polyether marine toxin isolated from sea anemones. It is one of the most toxic nonprotein substances, causing many people to be poisoned every year and to die in severe cases. Despite its known impact on Na+,K+-ATPase, much still remains unclear about PLTX's mechanism of action. Here, we tested different concentrations of PLTX on HaCaT cells and studied its distributions in cells, its impact on gene expression, and the associated pathways via proteomics combined with bioinformatics tools. We found that PLTX could cause ferroptosis in HaCaT cells, a new type of programmed cell death, by up-regulating the expression of VDAC3, ACSL4 and NCOA4, which lead to the occurrence of ferroptosis. PLTX also acts on the MAPK pathway, which is related to cell apoptosis, proliferation, division and differentiation. Different from its effect on ferroptosis, PLTX down-regulates the expression of ERK, and, as a result, the expressions of MAPK1, MAP2K1 and MAP2K2 are also lower, affecting cell proliferation. The genes from these two mechanisms showed interactions, but we did not find overlap genes between the two. Both ferroptosis and MAPK pathways can be used as anticancer targets, so PLTX may become an anticancer drug with appropriate modification.

Creating three-dimensional magnetic functional microdevices via molding-integrated direct laser writing.

Magnetically driven wireless miniature devices have become promising recently in healthcare, information technology, and many other fields. However, they lack advanced fabrication methods to go down to micrometer length scales with heterogeneous functional materials, complex three-dimensional (3D) geometries, and 3D programmable magnetization profiles. To fill this gap, we propose a molding-integrated direct laser writing-based microfabrication approach in this study and showcase its advanced enabling capabilities with various proof-of-concept functional microdevice prototypes. Unique motions and functionalities, such as metachronal coordinated motion, fluid mixing, function reprogramming, geometrical reconfiguring, multiple degrees-of-freedom rotation, and wireless stiffness tuning are exemplary demonstrations of the versatility of this fabrication method. Such facile fabrication strategy can be applied toward building next-generation smart microsystems in healthcare, robotics, metamaterials, microfluidics, and programmable matter.

Effect of GLP-1R rs2254336 and rs3765467 polymorphisms on gastrointestinal adverse reactions in type 2 diabetes patients treated with liraglutide.

PURPOSE: Gastrointestinal adverse reactions (GIARs) to liraglutide exhibit significant individual differences in type 2 diabetes. This study investigated the association between glucagon-like peptide-1 receptor (GLP-1R) single-nucleotide polymorphisms (SNPs) and GIARs. METHODS: Adverse events of liraglutide were observed in 376 T2DM patients. Seven tag SNPs at GLP-1R were sequenced in 152 participants. The influencing factors of GIARs and the genetic model of tag SNPs were examined by logistic regression analysis. The relationship between the tag SNPs and GIARs was determined by the chi-square test and cochran-armitage trend test. Multifactor dimensionality reduction (MDR) analysis was used to explore interactive analysis in GIARs risk. RESULTS: Twenty-nine percent of subjects had side effects, mainly GIARs. Nausea was the most common GIARs. Compared with males, females were more likely to develop GIARs (P = 0.043, OR = 1.895, 95% CI: 1.021-3.517). The T allele at GLP-1R rs2254336 (P = 0.028) and the A allele at GLP-1R rs3765467 (P = 0.007) were associated with GIARs of liraglutide. As the number of rs2254336 T alleles (P = 0.014) or rs3765467 A alleles (P = 0.008) increased, the subjects tended to develop GIARs. MDR analysis identified that there were no significant interactions among rs2254336, rs3765467 and sex. CONCLUSION: Our results suggest that female sex, the T allele at GLP-1R rs2254336 and the A allele at GLP-1R rs3765467 could be predictors of GIARs with liraglutide in T2DM patients.

Identification of prognostic metabolic genes in adrenocortical carcinoma and establishment of a prognostic nomogram: A bioinformatic study.

ABSTRACT: Adrenocortical carcinoma is an invasive malignancy with poor prognosis, high recurrence rate and limited therapeutic options. Therefore, it is necessary to establish an effective method to diagnose and evaluate the prognosis of patients, so as to realize individualized treatment and improve their survival rate.This study investigated metabolic genes that may be potential therapeutic targets for Adrenocortical carcinoma (ACC). Level 3 gene expression data from the ACC cohort and the relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. To verify, other ACC datasets (GSE76021, GSE19750) were downloaded from the Gene Expression Omnibus (GEO) database. The ACC datasets from TCGA and GEO were used to screen metabolic genes through the Molecular Signatures Database using gene set enrichment analysis. Then, the overlapping metabolic genes of the 2 datasets were identified.A signature of five metabolic genes (CYP11B1, GSTM2, IRF9, RPL31, and UBE2C) was identified in patients with ACC. The signature could be used to divide the patients with ACC into high- and low-risk groups based on their median risk score. Multivariate Cox regression analysis was performed to determine the independent prognostic factors of ACC. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to assess the prediction accuracy of the prognostic signature. Last, a nomogram was established to assess the individualized prognosis prediction model.The results indicated that the signature of 5 metabolic genes had excellent predictive value for ACC. These findings might help improve personalized treatment and medical decisions.

Association between Growth Differentiation Factor-15 and Risk of Cardiovascular Diseases in Patients with Adult Growth Hormone Deficiency.

OBJECTIVE: Patients with adult growth hormone deficiency (AGHD) confer a heightened risk of cardiovascular disease and increased mortality because of metabolic disorders. Growth differentiation factor-15 (GDF-15) plays an important role in predicting metabolic abnormalities. We sought to investigate the correlation between GDF-15 and cardiovascular risk in AGHD patients. METHODS: The study enrolled 80 AGHD patients and 80 healthy subjects. We analyzed the association between GDF-15 and some major biochemical indicators. The potential association between GDF-15 and cardiovascular disease risk was analyzed. RESULTS: The AGHD group exhibited increased waist-hip ratio and high-sensitivity C-reactive protein (hs-CRP) and lipid levels compared with the healthy control group. Serum GDF-15 levels in AGHD group were elevated significantly compared with the control group (P < 0.001). GDF-15 levels were negatively associated with insulin-like growth factor-1 in AGHD group (P=0.006) and positively correlated with waist-to-hip ratio (P=0.018), triglycerides (P=0.007), and hs-CRP (P=0.046). In addition, GDF-15 was positively correlated with Framingham risk score significantly after adjustment for other factors (r = 0.497, P < 0.001). Moreover, GDF-15 was an independent risk factor for cardiovascular disease in AGHD patients after adjusting for traditional cardiovascular risk factors. CONCLUSION: Elevated GDF-15 levels were significantly associated with cardiovascular risk factors and can be considered as a predictive biomarker of cardiovascular risk in AGHD patients.