Transcriptomic and metabolomic analyses reveal that lemon extract prolongs Drosophila lifespan by affecting metabolism.

Ageing is an evolutionarily conserved and irreversible biological process in different species. Numerous studies have reported that taking medicine is an effective approach to slow ageing. Lemon extract (LE) is a natural extract of lemon fruit that contains a variety of bioactive phytochemicals. Various forms of LE have been shown to play a role in anti-ageing and improving ageing-related diseases. However, studies on the molecular mechanism of LE in Drosophila ageing have not been reported. In this study, we found that 0.05 g/L LE could significantly extend Drosophila lifespan and greatly improve antioxidative and anti-heat stress abilities. Furthermore, transcriptome and metabolome analyses of 10 d flies between the LE-fed and control groups suggested that the differentially expressed gene ppo1 (Prophenoloxidase 1) and metabolite L-DOPA (Levodopa) were co-enriched in the tyrosine metabolism pathway. Overall, our results indicate that affecting metabolism was the main reason for LE extending Drosophila lifespan.

Protein expression patterns and metal metabolites in a protogynous hermaphrodite fish, the ricefield eel (Monopterus albus).

BACKGROUND: The ricefield eel Monopterus albus undergoes a natural sex change from female to male during its life cycle, and previous studies have shown the potential mechanisms of this transition at the transcriptional and protein levels. However, the changes in protein levels have not been fully explored, especially in the intersexual stage. RESULTS: In the present study, the protein expression patterns in the gonadal tissues from five different periods, the ovary (OV), early intersexual stage gonad (IE), middle intersexual stage gonad (IM), late intersexual stage gonad (IL), and testis (TE), were determined by untargeted proteomics sequencing. A total of 5125 proteins and 394 differentially expressed proteins (DEPs) were detected in the gonadal tissues. Of the 394 DEPs, there were 136 between the OV and IE groups, 20 between the IM and IE groups, 179 between the IL and IM groups, and 59 between the TE and IL groups. Three candidate proteins, insulin-like growth factor 2 mRNA-binding protein 3 isoform X1 (Igf2bp3), triosephosphate isomerase (Tpi), and Cu-Zn superoxide dismutase isoform X1 [(Cu-Zn) Sod1], were validated by western blotting to verify the reliability of the data. Furthermore, metal metabolite-related proteins were enriched in the IL vs. IM groups and TE vs. IL groups, which had close relationships with sex change, including Cu2+-, Ca2+-, Zn2+- and Fe2+/Fe3+-related proteins. Analysis of the combined transcriptome data revealed consistent protein/mRNA expression trends for two metal metabolite-related proteins/genes [LOC109953912 and calcium Binding Protein 39 Like (cab39l)]. Notably, we detected significantly higher levels of Cu2+ during the sex change process, suggesting that Cu2+ is a male-related metal metabolite that may have an important function in male reproductive development. CONCLUSIONS: In summary, we analyzed the protein profiles of ricefield eel gonadal tissues in five sexual stages (OV, IE, IM, IL, and TE) and verified the plausibility of the data. After preforming the functional enrichment of metal metabolite-related DEPs, we detected the contents of the metal metabolites Zn2+, Cu2+, Ca2+, and Fe2+/Fe3+ at these five stages and screened for (Cu-Zn) Sod1 and Mmp-9 as possible key proteins in the sex reversal process.

Population structure and adaptability analysis of Schizothorax o'connori based on whole-genome resequencing.

BACKGROUND: Schizothorax o'connori is an endemic fish distributed in the upper and lower reaches of the Yarlung Zangbo River in China. It has experienced a fourth round of whole gene replication events and is a good model for exploring the genetic differentiation and environmental adaptability of fish in the Qinghai-Tibet Plateau. The uplift of the Qinghai-Tibet Plateau has led to changes in the river system, thereby affecting gene exchange and population differentiation between fish populations. With the release of fish whole genome data, whole genome resequencing has been widely used in genetic evolutionary analysis and screening of selected genes in fish, which can better elucidate the genetic basis and molecular environmental adaptation mechanisms of fish. Therefore, our purpose of this study was to understand the population structure and adaptive characteristics of S. o'connori using the whole-genome resequencing method. RESULTS: The results showed that 23,602,746 SNPs were identified from seven populations, mostly distributed on chromosomes 2 and 23. There was no significant genetic differentiation between the populations, and the genetic diversity was relatively low. However, the Zangga population could be separated from the Bomi, Linzhi, and Milin populations in the cluster analysis. Based on historical dynamics analysis of the population, the size of the ancestral population of S. o'connori was affected by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Glacial Age. The selected sites were mostly enriched in pathways related to DNA repair and energy metabolism. CONCLUSION: Overall, the whole-genome resequencing analysis provides valuable insights into the population structure and adaptive characteristics of S. o'connori. There was no obvious genetic differentiation at the genome level between the S. o'connori populations upstream and downstream of the Yarlung Zangbo River. The current distribution pattern and genetic diversity are influenced by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Ice Age. The selected sites of S. o'connori are enriched in the energy metabolism and DNA repair pathways to adapt to the low temperature and strong ultraviolet radiation environment at high altitude.

Asymmetric Amination of Unstrained C(sp3)-C(sp3) Bonds.

The asymmetric functionalization of unstrained C(sp3)-C(sp3) bonds could be a powerful strategy to stereoselectively reconstruct the backbone of an organic compound, but such reactions are rare. Although allylic substitutions have been used frequently to construct C-C bonds by the cleavage of more reactive C-X bonds (X is usually an O atom of an ester) by transition metals, the reverse process that involves the replacement of a C-C bond with a C-heteroatom bond is rare and generally considered thermodynamically unfavorable. We show that an unstrained, inert allylic C-C σ bond can be converted to a C-N bond stereoselectively via a designed solubility-control strategy, which makes the thermodynamically unfavorable process possible. The C-C bond amination occurs with a range of amine nucleophiles and cleaves multiple classes of alkyl C-C bonds in good yields with high enantioselectivity. A novel resolution strategy is also reported that transforms racemic allylic amines to the corresponding optically active allylic amine by the sequential conversion of a C-N bond to a C-C bond and back to a C-N bond. Mechanistic studies show that formation of the C-N bond is the rate-limiting step and is driven by the low solubility of the salt formed from the cleaved alkyl group in a nonpolar solvent.

A gel-coated air-liquid-interface culture system with tunable substrate stiffness matching healthy and diseased lung tissues.

Since its invention in the late 1980s, the air-liquid-interface (ALI) culture system has been the standard in vitro model for studying human airway biology and pulmonary diseases. However, in a conventional ALI system, cells are cultured on a porous plastic membrane that is much stiffer than human airway tissues. Here, we develop a gel-ALI culture system by simply coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We determine the optimum gel thickness that does not impair the transport of nutrients and biomolecules essential to cell growth. We show that the gel-ALI system allows human bronchial epithelial cells (HBECs) to proliferate and differentiate into pseudostratified epithelium. Furthermore, we discover that HBECs migrate significantly faster on hydrogel substrates with stiffness matching that of fibrotic lung tissues, highlighting the importance of mechanical cues in human airway remodeling. The developed gel-ALI system provides a facile approach to studying the effects of mechanical cues in human airway biology and in modeling pulmonary diseases.NEW & NOTEWORTHY In a conventional ALI system, cells are cultured on a plastic membrane that is much stiffer than human airway tissues. We develop a gel-ALI system by coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We discover that human bronchial epithelial cells migrate significantly faster on hydrogel substrates with pathological stiffness, highlighting the importance of mechanical cues in human airway remodeling.

Exploration of Novel Meso-C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging.

The research on fluorescent rotors for viscosity has attracted extensive interest to better comprehend the close relationships of microviscosity variations with related diseases. Although scientists have made great efforts, fluorescent probes for cellular viscosity with both aggregation-induced emissions (AIEs) and large Stokes shifts to improve sensing properties have rarely been reported. Herein, we first report four new meso-C═N-substituted BODIPY-based rotors with large Stokes shifts, investigate their viscosity/AIE characteristics, and perform cellular imaging of the viscosity in subcellular organelles. Interestingly, the meso-C═N-phenyl group-substituted probe 6 showed an obvious 594 nm fluorescence enhancement in glycerol and a moderate 650 nm red AIE emission in water. Further, on attaching CF3 to the phenyl group, a similar phenomenon was observed for 7 with red-shifted emissions, attributed to the introduction of a phenyl group, which plays a key role in the red AIE emissions and large Stokes shifts. Comparatively, for phenyl-group-free probes, both the meso-C═N-trifluoroethyl group and thiazole-substituted probes (8 and 9) exhibited good viscosity-responsive properties, while no AIE was observed due to the absence of phenyl groups. For cellular experiments, 6 and 9 showed good lysosomal and mitochondrial targeting properties, respectively, and were further successfully used for imaging viscosity through the preincubation of monensin and lipopolysaccharide (LPS), indicating that C═N polar groups potentially work as rotatable moieties and organelle-targeting groups, and the targeting difference might be ascribed to increased charges of thiazole. Therefore, in this study, we investigated the structural relationships of four meso-C═N BODIPY-based rotors with respect to their viscosity/AIE characteristics, subcellular-targeting ability, and cellular imaging for viscosity, potentially serving as AIE fluorescent probes with large Stokes shifts for subcellular viscosity imaging.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Application status and optimization suggestions of tumor organoids and CAR-T cell co-culture models.

Tumor organoids, especially patient-derived organoids (PDOs) exhibit marked similarities in histopathological morphology, genomic alterations, and specific marker expression profiles to those of primary tumour tissues. They are applied in various fields including drug screening, gene editing, and identification of oncogenes. However, CAR-T therapy in the treatment of solid tumours is still at an exploratory stage. Tumour organoids offer unique advantages over other preclinical models commonly used for CAR-T therapy research, which the preservation of the biological characteristics of primary tumour tissue is critical for the study of early-stage solid tumour CAR-T therapies. Although some investigators have used this co-culture model to validate newly targeted CAR-T cells, optimise existing CAR-T cells and explore combination therapy strategies, there is still untapped potential in the co-culture models used today. This review introduces the current status of the application of tumour organoid and CAR-T cell co-culture models in recent years and commented on the limitations of the current co-cultivation model. Meanwhile, we compared the tumour organoid model with two pre-clinical models commonly used in CAR-T therapy research. Eventually, combined with the new progress of organoid technologies, optimization suggestions were proposed for the co-culture model from five perspectives: preserving or reconstructing the tumor microenvironment, systematization, vascularization, standardized culture procedures, and expanding the tumor organoids resource library, aimed at assisting related researchers to better utilize co-culture models.

Experimental Generation of Spin-Photon Entanglement in Silicon Carbide.

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

Stereoselective Synthesis of Polysubstituted Dihydropyrroles via 1,5-Addition and N-1,4-Addition Cascade.

An unprecedented 1,5-addition/N-1,4-addition cascade reaction is established via palladium hydride catalysis. A variety of polysubstituted dihydropyrrole skeletons are constructed in high yield and with exclusively >20 : 1 diastereoselectivity. An enantioselective protocol of this design is also developed to provide a novel access to enantioenriched dihydropyrroles.

Auranofin inhibits the occurrence of colorectal cancer by promoting mTOR-dependent autophagy and inhibiting epithelial-mesenchymal transformation.

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.

Effect of different working periods on missed diagnosis of colorectal polyps in colonoscopy.

BACKGROUND: To investigate the effect of different working periods on missed diagnoses in patients with colorectal polyps in colonoscopy. METHODS: We conducted a retrospective analysis of patients who were diagnosed with colorectal polyps during colonoscopy in an outpatient department between July and December 2022. These patients were subsequently hospitalized for resection during this period. Patients with missed diagnoses were those who had newly discovered polyps in a second colonoscopy. The working periods were categorized as work, near the end of work, and delayed work, respectively, in the morning and afternoon. RESULTS: A total of 482 patients were included, and the miss rate of diagnosis was 48.1% (232/482), mainly in the transverse colon (25%), and the ascending colon (23%). Patient age was a risk factor for the miss rate of diagnosis (OR = 1.025, 95%CI: 1.009-1.042, P = 0.003) and was also associated with the number of polyps detected for the first colonoscopy (χ2 = 18.196, P = 0.001). The different working periods had no statistical effect on the missed rate of diagnosis (χ2 = 1.998, P = 0.849). However, there was an increasing trend in miss rates towards the end of work and delayed work periods, both in the morning and afternoon. The highest miss rate (60.0%) was observed during delayed work in the afternoon. Additionally, poor bowel preparation was significantly more common during delayed work in the afternoon. CONCLUSIONS: The increasing trend in miss rates towards the end of work and delayed work periods deserves clinical attention. Endoscopists cannot always stay in good condition under heavy workloads.

Postoperative pancytopenia in a patient with giant parathyroid adenoma and brown tumor: a case report.

BACKGROUND: Parathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies. CASE PRESENTATION: We present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal. CONCLUSIONS: Pancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

Water compression induced ionic negative differential resistance in nanopores.

The mass transport behavior through nanoscale channels, greatly influenced by the structures and dynamics of nanoconfined water, plays an essential role in many biophysical processes. However, the dynamics of nanoconfined water under an external field and its effects are still not fully understood. Here, on the basis of molecular dynamics simulations, we theoretically show that the ionic current of [Bmim][PF6] through narrow pores in graphene membrane exhibits an ionic negative differential resistance effect-the ionic current decreases as the voltage increases over a certain threshold. This effect arises from the violation of traditional fluid dynamics as the assumption of continuity and homogeneity of fluids is no longer effective in ultrathin nanopores. The gradient of electric field around the atomic-thin layer produces a strong gradient force on the polarized water inside the nanopore. This dielectrophoretically compressed water leads to a hydrostatic force that repels ions from entering the nanopore. Our findings may advance the understanding of hydrostatic mechanism, which governs ion transport through nanopores.

Application Value of CYFRA21-1 Combined with NSE, CEA, and SCC-Ag in Lung Cancer.

BACKGROUND: This study aims to investigate the application value of serum cytokeratin 19 fragment (CYFRA21-1) combined with nerve-specific enolase (NSE), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) in the diagnosis of lung cancer (LC). METHODS: A total of 831 cases of LC, 360 cases of benign lung disease (BLD) and 102 healthy controls, were enrolled. The data were processed using SPSS, GraphPad Prism, and MedCalc software. RESULTS: The tumor marker (TM) levels in the LC and BLD groups were significantly higher than those in the control group; the CYFRA21-1, NSE, and CEA levels in the patients with LC were higher than in those with BLD. In particular, the increase was predominantly observed for the levels of CEA and CYFRA21-1 in adenocarcinoma (LUAD), CYFRA21-1 and SCC-Ag in squamous cell carcinoma (LUSC), and NSE in small cell carcinoma (SCLC). The CYFRA21-1, NSE, and CEA levels were significantly higher in stage IV than in other stages in LC. Univariate binary logistic analysis showed that increased levels of all four TMs were risk factors for BLD and LC. The area under the curve (AUC) of CYFRA21-1 was most effective in distinguishing patients with BLD or LC from the controls and in distinguishing patients with BLD and LC. The AUCs of combined CYFRA21-1, NSE, and CEA were increased to 0.755, 0.922, and 0.783, respectively, with no significant difference with the AUC of the four combined tests. In the histological classification, the best predictors were CEA, for LUAD, CYFRA21-1 for LUSC, and NSE for SCLC. Moreover, the expression levels of CYFRA21-1, NSE, and CEA significantly decreased after each treatment course. CONCLUSIONS: The combined assay of CYFRA21-1, NSE, and CEA addresses the aspects of accuracy, sensitivity, specificity, and economic cost and should be considered as a potential diagnostic test in LC.

Analysis of influencing factors of HPV vaccination willingness of female sex workers in urban entertainment venues based on the IMB model in Guangxi, China.

OBJECTIVE: Understanding HPV vaccination willingness and its influencing factors among female sex workers (FSWs) in entertainment venues in an urban area of Guangxi, China. METHODS: From 15 August to 15 October 2022, FSWs in entertainment venues with commercial sex trade in an urban area of Guangxi were selected as the study subjects for the questionnaire survey using the method of intentional sampling. The questionnaire based on the information-motivation-behavior (IMB) skills model was used to collect the basic characteristics, HPV and HPV vaccine-related information and cognition, motivation to vaccinate, behavioral skills and willingness to vaccinate from the research targets. A multifactor logistic regression model was used to analyze the factors influencing the research targets' willingness to receive HPV vaccination. RESULTS: Of the 921 research targets, 712 (77.31%) were willing to receive HPV vaccination. The higher the level of knowledge regarding HPV and HPV vaccine-related information, the higher the motivation for HPV vaccination. In addition, the higher the behavioral skills score, the higher the willingness of FSWs in entertainment venues to receive HPV vaccination (P<0.001). FSWs in entertainment venues with lower venue grades [OR(95% CI)=0.693 (0.539, 0.891), P=0.004] were more reluctant to receive HPV vaccination. Those who favored the effectiveness of the vaccine in preventing the disease [OR(95% CI)=2.144 (1.449, 3.174), P<0.001] and those who had heard of HPV vaccine [OR(95% CI)=2.105 (1.451, 3.054), P<0.001], were able to perceive the benefits of HPV vaccination [OR(95% CI)=1.134 (1.045, 1.230), P=0.002]. These individuals acquired greater behavioral skills i.e., self-decision making for HPV vaccination [OR(95% CI)=1.130 (1.008, 1.267), P=0.036] and self-efficacy [OR(95% CI)=1.135 (1.081, 1.191), P<0.001] and they were more willing to receive HPV vaccine. CONCLUSIONS: There was a relatively high HPV vaccination willingness among FSWs in entertainment venues in an urban area of Guangxi, China. Attention should be focused on introducing the benefits of primary prevention measures such as the HPV vaccine for individuals and behavioral skills for HPV vaccination in order to increase their willingness to be vaccinated thus increasing their HPV vaccination rate.

Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients.

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.

The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.

Application of fecal collection device in Intensive Care Unit Patients with fecal incontinence Receiving Extracorporeal Membrane Oxygenation: A Comparison Cohort Study.

Objective: The objective of this study was to assess the effectiveness of fecal collection devices in preventing incontinence-associated dermatitis (IAD) and reducing skin care time in ICU patients with fecal incontinence undergoing Extracorporeal Membrane Oxygenation (ECMO). Methods: A nonrandomized comparison cohort (quasi-experimental) study with pre-post comparison was carried out in a general intensive care unit. 85 bedridden patients receiving ECMO with fecal incontinence (FI) in a general intensive care unit between June 2017 and May 2022 participated in the study and separated into two groups according to the fecal collection device they received. 40 were assigned to the Control group (structured IAD preventive care protocol alone) and 45 to the Intervention group (structured IAD preventive care protocol plus application of fecal collection device). The status of IAD was assessed using the Incontinence Associated Dermatitis Intervention Tool (IAD-IT). Fecal consistency was evaluated via the Bristol Stool Scale. Outcome measures included the nursing time for skin care and the incidence of IAD, and bleeding complications between the two groups during the period. Results: Participants in the Intervention group had fewer IAD occurrences than participants in the Control group (13.33% vs. 52.50%, P < .05). The patients in the Intervention group significantly reduced skincare time (63.30±14.09 min in the Control group versus 28.44±2.04 min in the Intervention group, P < .01). There was 3 turning complications for bleeding in the Intervention group and 11 in the Control group and had a significant reduction in urning complications(3 vs.11, P = .022). Conclusions: Applying a fecal collection device may reduce skincare time and reduce occurrences of IAD and bleeding related to turning position for skin care in ICU patients with FI associated with diarrhea receiving ECMO Support.This study offers a more efficient way to use the fecal collection device in ECMO patients.Future research needs to focus on the perianal skin in ECMO patients regarding fecal collection devices connected to continuous low-negative-pressure suction devices.

The DDD score outperforms the RENAL score in predicting high-grade renal cell carcinoma.

OBJECTIVES: To explore the relationship between Fuhrman grade of renal cell carcinoma (RCC) and the DDD score. METHODS: We reviewed the records of 527 nonmetastatic RCC patients. Demographic, clinical, and pathologic characteristics were reviewed. Binary logistic regression was used to explore the independent risk factors for high-grade RCC (HGRCC). RESULTS: Sex, BMI (Body Mass Index), RNS, and DDD score were significantly correlated with HGRCC. Based on these independent risk factors, we constructed two predictive models integrating the RNS and DDD scores with sex and BMI to predict tumor grade. The calibration curves of the predictive model showed good agreement between the observations and predictions. The concordance indexes (C-indexes) of the predictive models were 0.768 (95% CI, 0.713-0.824), and 0.809 (95% CI, 0.759-0.859). Receiver operating characteristic (ROC) curves were performed to compare the predictive power of the nomograms, and the prediction model including the DDD score had better prognostic ability (p = 0.01). CONCLUSIONS: This study found that RNS, DDD score, BMI, and sex were independent predictors of HGRCC. We developed effective nomograms integrating the above risk factors to predict HGRCC. Of note, the nomogram including the DDD score achieves better prediction ability for HGRCC.