Worldwide burden and trends of diabetes among people aged 70 years and older, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Diabetes places a significant burden on personal and public health. However, a comprehensive assessment of the burden of diabetes in older adults is lacking. We aimed to estimate the global burden of diabetes and explore trends for the population aged ≥70 from 1990 to 2019. METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the prevalence, mortality, and disability-adjusted life-years (DALYs) of diabetes among people aged ≥70 were estimated by sex and age group in 2019. We also assessed the epidemiological trend of diabetes from 1990 to 2019. RESULTS: In 2019, 110.1 million (95% uncertainty interval [UI]: 101.2-119.4) people aged ≥70 years were living with diabetes (types 1 and 2 combined) with a global prevalence of 23.7% (21.8%-25.8%). Worldwide, 181.9 deaths (163.0-194.7) per 100,000 population and 4512.3 DALYs (3861.3-5264.2) per 100,000 population occurred due to diabetes. In 2019, minor sex-related disparities in the burden of diabetes were identified among specific age and sex groups. From 1990 to 2019, the prevalence of diabetes increased by 39.7% (37.7%-41.7%), and the related mortality and DALY rates also increased (16.4% [9.43%-22.9%] and 22.3% [17.2%-27.0%], respectively). CONCLUSION AND RELEVANCE: The global burden of diabetes in adults aged ≥70 has increased markedly from 1990 to 2019. As the population continues to age, there is an urgent need to combat the increasing disease burden.

Piezoresistive Porous Composites with Triply Periodic Minimal Surface Structures Prepared by Self-Resistance Electric Heating and 3D Printing.

Three-dimensional flexible piezoresistive porous sensors are of interest in health diagnosis and wearable devices. In this study, conductive porous sensors with complex triply periodic minimal surface (TPMS) structures were fabricated using the 3D printed sacrificial mold and enhancement of MWCNTs. A new curing routine by the self-resistance electric heating was implemented. The porous sensors were designed with different pore sizes and unit cell types of the TPMS (Diamond (D), Gyroid (G), and I-WP (I)). The impact of pore characteristics and the hybrid fabrication technique on the compressive properties and piezoresistive response of the developed porous sensors was studied. The results indicate that the porous sensors cured by the self-resistance electric heating could render a uniform temperature distribution in the composites and reduce the voids in the walls, exhibiting a higher elastic modulus and a better piezoresistive response. Among these specimens, the specimen with the D-based structure cured by self-resistance electric heating showed the highest responsive strain (61%), with a corresponding resistance response value of 0.97, which increased by 10.26% compared to the specimen heated by the external heat sources. This study provides a new perspective on design and fabrication of porous materials with piezoresistive functionalities, particularly in the realm of flexible and portable piezoresistive sensors.

Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway.

BACKGROUND: Gastric cancer is a serious malignant tumor associated with aberrant circular RNAs (circRNAs) expression. In this study, we aim to investigate the role and the underlying mechanism of circ_0000190, a circRNA in gastric cancer. METHODS: Circ_0000190 expression in vivo was examined in gastric cancer and adjacent normal tissues by RT-PCR. Circ_0000190 expression in gastric cancer cell lines was detected by FISH and RT-PCR. The role of the circRNA in gastric cancer cells was assessed by the analysis of cell viability, apoptosis, proliferation, cell cycle and migration. The potential effector of circ_0000190 was predicted by computational screen and validated by luciferase reporter assay. Furthermore, Mice model of human gastric cancer was established to observe the underlying mechanisms of circ_0000190. RESULTS: Circ_0000190 was down-regulated in gastric cancer tissues and cells, with a major location in cytoplasm. Circ_0000190 inhibited gastric cancer cell viability, proliferation and migration, and induced apoptosis and cell cycle arrest by regulating the expression of capase-3, p27 and cyclin D. In addition, the circRNA was validated as a sponge of miR-1252, which directly targeted PAK3. The effects of circ_0000190 on the cellular processes were blocked by miR-1252 mimics, which could be rescued after further overexpression of PAK3. CONCLUSIONS: Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway, employing circ_0000190 might be a promising therapeutic strategy for the treatment of gastric cancer.

Novel Model Predicts Diabetic Nephropathy in Type 2 Diabetes.

BACKGROUND: Clinical indicators for accurately distinguishing diabetic nephropathy (DN) from non-diabetic renal disease in type 2 diabetes (T2D) are lacking. This study aimed to develop and validate a nomogram for predicting DN in T2D patients with kidney disease. METHODS: A total of 302 consecutive patients with T2D who underwent renal biopsy at China-Japan Friendship Hospital between January 2014 and June 2019 were included in the study. The data were randomly split into a training set containing 70% of the patients (n = 214) and a validation set containing the remaining 30% of patients (n = 88). Multivariable logistic regression analyses were applied to develop a prediction nomogram incorporating the candidates selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using a concordance index (C-index), calibration plot, and decision curve analysis. Both internal and external validations were assessed. RESULTS: A multivariable model that included gender, diabetes duration, diabetic retinopathy, hematuria, glycated hemoglobin A1c, anemia, blood pressure, urinary protein excretion, and estimated glomerular filtration rate was represented as the nomogram. The model demonstrated very good discrimination with a C-index of 0.934 (95% CI 0.904-0.964). The calibration plot diagram of predicted probabilities against observed DN rates indicated excellent concordance. The C-index value was 0.91 for internal validation and 0.875 for external validation. Decision curve analysis demonstrated that the novel nomogram was clinically useful. CONCLUSION: The novel model was very useful for predicting DN in patients with T2D and kidney disease, and thereby could be used by clinicians either in triage or as a replacement for biopsy.

Electroacupuncture Improves Cognition in Rats With Sepsis-Associated Encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common complication of sepsis. Although sepsis is effectively managed with the administration of antibiotics and source control, which may include surgical intervention, SAE usually leads to prolonged cognitive dysfunction affecting the quality of life of the patients. In this study, we investigated the possible effect of electroacupuncture (EA) on cognition in a model of SAE induced by cecal ligation and puncture (CLP). MATERIALS AND METHODS: The rats were randomly divided into four groups: the control group, the CLP group, the CLP with EA treatment group (CLP + EA), and the CLP with sham EA treatment group (CLP + sham EA). EA at DU20, LI11, and ST36 or sham EA was performed 30 min daily for 10 consecutive days starting from 2 days before CLP. Then cognitive function was examined by the Morris water maze test. On day 14 after CLP surgery, the synaptic injury, neuron loss, and oxidative stress were studied. RESULTS: Rats with EA treatment showed improved survival rate, spatial learning, and memory abilities. The dendritic spine density, the synaptic proteins, and the hippocampal neuron number were also increased after EA treatment. Furthermore, EA suppressed oxidative stress through regulating the level of malondialdehyde and superoxide dismutase and enhanced the expression of antioxidant nuclear factor erythroid-2-related factor-2 and hemeoxygenase-1. But sham EA did not have the same effect. CONCLUSIONS: EA may protect against SAE-induced cognitive dysfunction by inhibiting synaptic injury, neuronal loss, and oxidative stress, and the nuclear factor erythroid-2-related factor-2/hemeoxygenase-1 signaling pathway may be involved in this effect.

Activation mechanisms and multifaceted effects of mast cells in ischemia reperfusion injury.

Mast cells (MCs) are tissue resident effector cells that form an important part of the immune system's first-line of defence against various pathogenic challenges. They are well known for their roles in anaphylaxis and allergy; however, increasing evidence implicates MCs in a wide range of pathologies. Ischemia/reperfusion (I/R) injury elicits an inflammatory response and triggers the program of tissue damage and restoration, as well as immune regulation. MCs are uniquely distributed around microvasculature and potentially the first responders to early or specific aspects of IR pathogenesis through the release of preformed mediators of MC granule. Versatility and extreme heterogeneity are hallmarks of MCs, resulting from different adaptions acquired during phylogenesis; such plasticity is also highlighted during MC development. Thus, it is necessary to discuss the functions of the MC population that could differ depending on the tissue in which they reside, and various effects of MCs can be induced by stimuli during I/R. In this review, we primarily discuss the contribution of MC activation in I/R injuries of hepatic, pulmonary, myocardial, cerebral, renal, and intestinal organs or systems. A further understanding of the mechanisms underlying the role of MCs in I/R injuries would aid the development of specific MC-targeted therapeutics to protect against some specific injury, such as negating the proinflammatory roles of some specific MC mediators.

FOXO1: Another avenue for treating digestive malignancy?

Digestive malignancies are the leading cause of mortality among all neoplasms, contributing to estimated 3 million deaths in 2012 worldwide. The mortality rate hassurpassed lung cancer and prostate cancer in recent years. The transcription factor Forkhead Box O1 (FOXO1) is a key member of Forkhead Box family, regulating diverse cellular functions during tumor initiation, progression and metastasis. In this review, we focus on recent studies investigating the antineoplastic role of FOXO1 in digestive malignancy. This review aims to serve as a guide for further research and implicate FOXO1 as a potent therapeutic target in digestive malignancy.

The development of methods for primary mast cells in vitro and ex vivo: An historical review.

Mast cells (MCs) are tissue-based stationary effector cells that form the immune system's first-line defense against various challenges. They are developed from the bone marrow-derived progenitors to complete their differentiation and maturation in the tissues where they eventually establish residence. MCs have been implicated in many diseases, such as allergy, parasitic infection, and neoplastic disorders. Immortalized MC lines, such as RBL-2H3, HMC-1, and LAD-2, are useful for investigating the biological functions of MC only to some extents due to the restriction of degranulation evaluation, in vivo injection and other factors. Over the past few decades, technologies for acquiring primarily MCs have been continually optimized, and novel protocols have been proposed. However, no relevant publications have analyzed and summarized these techniques. In this review, the classical approaches for extracting MCs are generalized, and new methods with potential values are introduced. We also evaluate the advantages and applicability of diverse MC models. Since MCs exhibit substantial plasticity and functional diversity due to different origins, it is both necessary and urgent to select a reliable and suitable source of MCs for a particular study.

Clinical feasibility and safety of third space robotic and endoscopic cooperative surgery for gastric gastrointestinal stromal tumors dissection : A new surgical technique for treating gastric GISTs.

BACKGROUND: Surgical management of gastric gastrointestinal stromal tumors (GISTs) has evolved towards minimal invasiveness. Laparoscopic wedge resection and laparoscopic and endoscopic cooperative surgery had been considered as standard surgical treatments for gastric GISTs > 2 cm. However, stomach deformation and the full-thickness gastric defect caused by these procedures may increase the risk of morbidity. To address these problems, we developed a novel technique, third space robotic and endoscopic cooperative surgery (TS-RECS), which could dissect the tumor entirely while preserving the intact mucosal layer. Here we performed a prospective evaluation of the feasibility and safety of TS-RECS. METHODS: Patients with gastric GISTs were recruited between April 2018 and April 2019. During the operation, the gastric GIST was located by endoscopic view firstly and the submucosal injection was performed. The tumor was then dissected through robotic surgery. Clinicopathological characteristics, operative data, adverse events, and follow-ups were prospectively collected and analyzed. RESULTS: A total of 20 patients with gastric GISTs received TS-RECS. The mean tumor size was 33.0 ± 7.3 mm. R0 resection was achieved in all patients with a median operation time of 115 min and a median blood loss of 20 ml. The integrity of mucosal layer was maintained in 95% (19/20) of the patients. All patients started oral diet on postoperative day 1 or 2, staying in the hospital for a median of 6 days after surgery. There were no major adverse events. Local or distant recurrences were not observed during a median follow-up period of 10 months. CONCLUSIONS: Our study suggests that TS-RECS appears to be a feasible and safe technique which could be an alternative method for resecting gastric GISTs > 2 cm. CLINICAL TRIALS: ClinicalTrials.gov NCT03804762.

High-Dose RAI Therapy Justified by Pathological N1a Disease Revealed by Prophylactic Central Neck Dissection for cN0 Papillary Thyroid Cancer Patients: Is it Superior to Low-Dose RAI Therapy?

OBJECTIVE: One of the presumed advantages of prophylactic central neck dissection (pCND) is offering staging basis for more aggressive radioactive iodine (RAI) therapy, which postulates the necessity of high dose for treatment efficacy. The present study aims to compare the effectiveness between low-dose and high-dose RAI in a select cohort of cN0 papillary thyroid cancer (PTC) patients with pathological N1a (pN1a) disease revealed by pCND in terms of ablation rate and response to therapy. The frequency of short-term adverse effects between the two groups was also compared. PATIENTS AND METHODS: From January 2014 to April 2016, cN0 PTC patients with pN1a disease revealed by pCND in our hospital were retrospectively reviewed. Patients with other indications for high-dose RAI, such as the presence of extrathyroidal extension, vascular invasion or suspicions of distant metastasis, were excluded. For the included patients, high dose (3700 MBq) was administered between January 2014 and August 2015 and low dose (1110 MBq) between August 2015 and April 2016. Ablation assessment was performed 6 months after RAI therapy. Response evaluation after RAI therapy was performed after 46.3 ± 9.5 months for high-dose group and 29.1 ± 2.6 months for low-dose group. All patients were also evaluated for short-term adverse effects 24 and 72 hours after RAI administration. RESULTS: A total of 84 patients were enrolled. Among them, 42 were in the high-dose group and the other 42 in the low-dose group. There was no significant difference in ablation rate (P = 0.7707) and response to RAI therapy (P = 0.6454) between the two groups. Twenty-four hours after RAI administration, neck pain and swelling (33.3% VS. 11.9%; P = 0.0372) and gastrointestinal discomfort (45.2% vs. 21.4%; P = 0.0373) were significantly more frequent in the high-dose group. CONCLUSION: High-dose RAI therapy, with higher frequency of short-term adverse effects, appears to be not superior to low-dose RAI therapy for cN0 PTC patients with pN1a disease revealed by pCND to achieve better response to therapy. Further randomized studies with larger series of patients and longer follow-up duration, especially with the low-dose group, are needed to validate our results.

Diagnostic Performance of Retinopathy in the Detection of Diabetic Nephropathy in Type 2 Diabetes: A Systematic Review and Meta-Analysis of 45 Studies.

AIMS: To conduct an evidence-based evaluation of diabetic retinopathy (DR) for the diagnosis of diabetic nephropathy (DN) in type 2 diabetics with kidney disease. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library from inception to June 27, 2018, including the reference lists of identified primary studies. A study was included if it (1) used DR as a diagnostic test for DN; and (2) used histological evaluation of renal tissues as the reference standard. RESULTS: The analysis included 45 studies (4,561 patients). A bivariate analysis yielded a sensitivity of 0.67 (95% CI 0.61-0.74) and a specificity of 0.78 (95% CI 0.73-0.82). The summary receiver operating characteristic curve analysis provided an area under the curve (AUC) of 0.79 (95% CI 0.76-0.83). In a setting of 41% prevalence of DN, the probability of DN would be 68% if the test of DR was positive, and the probability of DN would be 23% if it was negative. In addition, although the mean specificity of proliferative DR for the detection of DN was 0.99 (95% CI 0.45-1.00), the mean sensitivity was 0.34 (95% CI 0.24-0.44), and the AUC was 0.58 (95% CI 0.53-0.62). CONCLUSIONS: DR is helpful in diagnosing DN in persons with type 2 diabetes and kidney disease, but the severity of DR may not parallel the presence of DN.

In Vivo Mitigation of Amyloidogenesis through Functional-Pathogenic Double-Protein Coronae.

Amyloid diseases are global epidemics with no cure available. Herein, we report a first demonstration of in vivo mitigation of amyloidogenesis using biomimetic nanotechnology. Specifically, the amyloid fragments (ba) of ß-lactoglobulin, a whey protein, were deposited onto the surfaces of carbon nanotubes (baCNT), which subsequently sequestered human islet amyloid polypeptide (IAPP) through functional-pathogenic double-protein coronae. Conformational changes at the ba-IAPP interface were studied by Fourier transform infrared, circular dichroism, and X-ray scattering spectroscopies. baCNT eliminated the toxic IAPP species from zebrafish embryos, as evidenced by the assays of embryonic development, cell morphology, hatching, and survival as well as suppression of oxidative stress. In addition to IAPP, baCNT also displayed high potency against the toxicity of amyloid-ß, thereby demonstrating the broad applicability of this biomimetic nanotechnology and the use of an embryonic zebrafish model for the high-throughput screening of a range of amyloidogenesis and their inhibitors in vivo.

The structure of denitrifying microbial communities in constructed mangrove wetlands in response to fluctuating salinities.

In this study, the experimental vertical-flow constructed wetland (CW) systems planted with the salt-tolerant mangrove species Kandelia candel were established to investigate the influence of salinity fluctuations on the denitrification performance and denitrifying microbial community structure of the CWs. The high-throughput sequencing analysis showed that 10-13 genera aerobic microbes had been enriched in the upper layer of wetland matrix in the depth of 10-25 cm, with the relative abundance accounting for 19.1 ±â€¯7.9%. Although the ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) were inhibited significantly in the CW systems with salinity levels in the range of 0.9-1.8%, the aerobic denitrifying (AD) bacteria including Pseudomonas, Acinetobacter and Aeromonas, removed 99% of ammonia nitrogen from the influent by heterotrophic nitrification (HN) functions, and conducted denitrification at the same time to remove 90% of the TN in the system, indicating that the wetland test system successfully enriched a variety of aerobic denitrifying bacterial communities under different salinity conditions. Not only the nitrogen removal efficiency but also the adaptability of the wetland system to salinity fluctuations had been improved by the enriched HN-AD bacteria. In addition, HN-AD bacterial communities can conduct both nitrification and denitrification in the middle and upper layers of the vertical flow wetland, hereby saving the reaction space of the constructed wetland and reducing the construction cost.

Identification of serum proteins AHSG, FGA and APOA-I as diagnostic biomarkers for gastric cancer.

BACKGROUND: The development of clinically accessible biomarkers is critical for the early diagnosis of gastric cancer (GC) in patients. High-throughput proteomics techniques could not only effectively generate a serum peptide profile but also provide a new approach to identify potentially diagnostic and prognostic biomarkers for cancer patients. METHODS: In this study, we aim to identify potentially discriminating serum biomarkers for GC. In the discovery cohort, we screened potential biomarkers using magnetic-bead-based purification and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in 64 samples from 32 GC patients that were taken both pre- and post-operatively and 30 healthy volunteers that served as controls. In the validation cohort, the expression patterns and diagnostic values of serum FGA, AHSG and APOA-I were further confirmed by ELISA in 42 paired GC patients (pre- and post-operative samples from 16 patients with pathologic stage I/II and 26 with stage III/IV), 30 colorectal cancer patients, 30 hepatocellular carcinoma patients, and 28 healthy volunteers. RESULTS: ClinProTools software was used and annotated 107 peptides, 12 of which were differentially expressed among three groups (P < 0.0001, fold > 1.5). These 12 peptide peaks were further identified as FGA, AHSG, APOA-I, HBB, TXNRD1, GSPT2 and CAKP5. ELISA data suggested that the serum levels of FGA, AHSG and APOA-I in GC patients were significantly different compared with healthy controls and had favorable diagnostic values for GC patients. Moreover, we found that the serum levels of these three proteins were associated with TNM stages and could reflect tumor burden. CONCLUSION: Our findings suggested that FGA, AHSG and APOA-I might be potential serum biomarkers for GC diagnosis.

Degranulation of gastrointestinal mast cells contributes to hepatic ischemia-reperfusion injury in mice.

The pathological changes following liver damage, including those caused by ischemia and reperfusion (I/R), are closely related to gastrointestinal dysregulation. Mast cells (MCs) are tissue-resident immune cells abundant in the gastrointestinal system that play diverse roles. In view of the characteristic localization of MCs around the microvasculature, we hypothesized that a stimulus-specific set of mediators released through degranulation of gastrointestinal MCs, which are enriched in hepatic sinusoids via the hepatic system, subsequently participate in associated pathological development within the liver. To elucidate the biological role of gastrointestinal MC granules in liver damage, we employed an experimental liver I/R model that allows conditional ablation of MCs. Marked degranulation was detected during I/R, which showed a significant positive correlation with liver damage. Our experiments further disclosed that MC degranulation primarily enhanced the cycle of inflammatory damage in I/R liver consisting of liver sinusoidal endothelial cell death, neutrophil infiltration, and formation of a neutrophil extracellular trap, with a concomitant increase in adhesion molecules, inflammatory cytokines, chemokines, and oxidative stress. Based on the collective results, we propose that suppression of activity or number of MCs may present an effective strategy for protection against hepatic I/R injury.

Increased Local Sympathetic Nerve Activity During Pathogenesis of Ventricular Arrhythmias Originating from the Right Ventricular Outflow Tract.

BACKGROUND The contribution of local sympathetic nerves to ventricular arrhythmia (VA) originating from the right ventricular outflow tract (RVOT) has not been elucidated. This study used a canine model to investigate the anatomical changes of the RVOT associated with VA, and the distribution of local sympathetic nerves. MATERIAL AND METHODS The RVOT-VA canine model (6 dogs) was induced with a circular catheter and high-frequency stimulation (100 Hz) in the middle of the pulmonary artery trunk. Six dogs who were not given stimulation served as the control group. The serum levels of neurotransmitters, the extent of myocardial extension, and the sympathetic nerve density of the RVOT were also analyzed. RESULTS Ventricular arrhythmias, including premature ventricular contractions, were induced in the experimental group after high-frequency stimulation. Dogs from the RVOT-VA group showed enhanced myocardial extension and sympathetic nerve density in the septal wall as compared with those of the free wall of the RVOT. In the RVOT-VA dogs, serum norepinephrine and neuropeptide Y and the sympathetic nerve density were significantly higher compared with the control group. CONCLUSIONS Stimulation of the pulmonary artery could activate local sympathetic nerves and enhance myocardial extension, which may be the foundation of RVOT-VA. The RVOT voltage transitional zone positively correlated with myocardial extension, which may serve as an important target for the radiofrequency catheter ablation of RVOT-VA clinically.

DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice.

Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages.

Integrated Multi-omics Analyses Identify CDCA5 as a Novel Biomarker Associated with Alternative Splicing, Tumor Microenvironment, and Cell Proliferation in Colon Cancer Via Pan-cancer Analysis.

Background: CDCA5 has been reported as a gene involved in the cell cycle, however current research provides little details. Our goal was to figure out its functions and probable mechanisms in pan-cancer. Methods: Pan-cancer bulk sequencing data and web-based analysis tools were applied to analyze CDCA5's correlations with the gene expression, clinical prognosis, genetic alterations, promoter methylation, alternative splicing, immune checkpoints, tumor microenvironment and enrichment. Real­time PCR, cell clone formation assay, CCK-8 assay, cell proliferation assay, migration assay, invasion assay and apoptosis assay were used to evaluate the effect of CDCA5 silencing on colon cancer cell lines. Results: CDCA5 is highly expressed in most tumors, which has been linked to a poor prognosis. Immune checkpoints analysis revealed that CDCA5 was associated with the immune gene CD276 in various tumors. Single-cell analysis showed that CDCA5 correlated with proliferating T cell infiltration in COAD. Enrichment analysis demonstrated that CDCA5 may modify cell cycle genes to influence p53 signaling. The examination of DLD1 cells revealed that CDCA5 increased the proliferation and blocked cell apoptosis. Conclusion: This study contributes to the knowledge of the role of CDCA5 in carcinogenesis, highlighting the prognostic potential and carcinogenic involvement of CDCA5 in pan-cancer.

A prognostic nomogram integrating carcinoembryonic antigen levels for predicting overall survival in elderly patients with stage II-III colorectal cancer.

Background: With the aging of the population, colorectal surgeons will have to face more elderly colorectal cancer (CRC) patients in the future. We aim to analyze independent risk factors affecting overall survival in elderly (age ≥65 years) patients with stage II-III CRC and construct a nomogram to predict patient survival. Methods: A total of 3,016 elderly CRC patients with stage II-III were obtained from the SEER database. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen independent prognostic factors, and a survival prediction nomogram was constructed based on the results. The consistency index (C-index), decision curve analysis (DCA), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were used to compare the predictive ability between the nomogram and tumor-node-metastasis (TNM) stage system. All patients were classified into high-risk and low-risk groups based on risk scores calculated by nomogram. The Kaplan-Meier method was used to compare the survival differences between two groups. Results: The 3- and 5-year area under the curve (AUC) values of the prediction nomogram model were 76.6% and 74.8%, respectively. The AIC, BIC, and C-index values of the nomogram model were 6,032.502, 15,728.72, and 0.707, respectively, which were better than the TNM staging system. Kaplan-Meier survival analysis showed a significant survival difference between high-risk and low-risk groups (P<0.0001). Conclusions: We constructed a prediction nomogram for stage II-III elderly CRC patients by combining pre-treatment carcinoembryonic antigen (CEA) levels, which can accurately predict patient survival. This facilitates clinicians to accurately assess patient prognosis and identify high-risk patients to adopt more aggressive and effective treatment strategies.

Unraveling the interplay of ferroptosis and immune dysregulation in diabetic kidney disease: a comprehensive molecular analysis.

BACKGROUND: Diabetic kidney disease (DKD) is a primary microvascular complication of diabetes with limited therapeutic effects. Delving into the pathogenic mechanisms of DKD and identifying new therapeutic targets is crucial. Emerging studies reveal the implication of ferroptosis and immune dysregulation in the pathogenesis of DKD, however, the precise relationship between them remains not fully elucidated. Investigating their interplay is pivotal to unraveling the pathogenesis of diabetic kidney disease, offering insights crucial for targeted interventions and improved patient outcomes. METHODS: Integrated analysis, Consensus clustering, Machine learning including Generalized Linear Models (GLM), RandomForest (RF), Support Vector Machine (SVM) and Extreme Gradient Boosting (xGB), Artificial neural network (ANN) methods of DKD glomerular mRNA sequencing were performed to screen DKD-related ferroptosis genes.CIBERSORT, ESTIMATE and ssGSEA algorithm were used to assess the infiltration of immune cells between DKD and control groups and in two distinct ferroptosis phenotypes. The ferroptosis hub genes were verified in patients with DKD and in the db/db spontaneous type 2 diabetes mouse model via immunohistochemical and Western blotting analyses in mouse podocyte MPC5 and mesangial SV40-MES-13 cells under high-glucose (HG) conditions. RESULTS: We obtained 16 differentially expressed ferroptosis related genes and patients with DKD were clustered into two subgroups by consensus clustering. Five ferroptosis genes (DUSP1,ZFP36,PDK4,CD44 and RGS4) were identified to construct a diagnostic model with a good diagnosis performance in external validation. Analysis of immune infiltration revealed immune heterogeneity between DKD patients and controls.Moreover, a notable differentiation in immune landscape, comprised of Immune cells, ESTIMATE Score, Immune Score and Stromal Score was observed between two FRG clusters. GSVA analysis indicated that autophagy, apoptosis and complement activation can participate in the regulation of ferroptosis phenotypes. Experiment results showed that ZFP36 was significantly overexpressed in both tissue and cells while CD44 was on the contrary.Meanwhile,spearman analysis showed both ZFP36 and CD44 has a strong correlation with different immune cells,especially macrophage. CONCLUSION: The regulation of the immune landscape in DKD is significantly influenced by the focal point on ferroptosis. Newly identified ferroptosis markers, CD44 and ZFP36, are poised to play essential roles through their interactions with macrophages, adding substantial value to this regulatory landscape.