The correlation between HOMA-IR and cardiometabolic risk index among different metabolic adults: a cross-sectional study.

AIMS: This study aimed to explore the correlation between homeostasis model assessment of insulin resistance(HOMA-IR)and cardiometabolic risk index(CMRI) among different metabolic adults to evaluate the value of HOMA-IR in predicting cardiometabolic risk. METHODS: This cross-sectional study was conducted over 18 months (from August 1, 2020 to February 18, 2022) and included 1550 participants divided into non-metabolic syndrome (non-MetS) group (n = 628) and metabolic syndrome (MetS) group (n = 922) in three centers of China. Logistic regression analysis was employed to investigate the correlation between HOMA-IR, body fat percentage, BMI (body mass index), visceral fat index, waist-to-hip ratio, vitamin D, and CMRI. Further analysis was conducted to evaluate the ability of HOMA-IR in diagnosing high CMRI within different metabolic, gender, and age groups to predict the risk of cardiovascular disease (CVD). RESULTS: HOMA-IR was significantly higher in the MetS group compared with the non-MetS group (P < 0.05). CMRI was significantly higher in the MetS group compared to the non-MetS group (P < 0.05). According to ROC curve analysis, HOMA-IR can predict cardiovascular risk (CVR) in the general population, non-MetS individuals, and MetS people. Logistic regression analysis revealed that BMI, visceral fat index, waist-to-hip ratio, and HOMA-IR are independent risk indicators of high CVR, whereas vitamin D may exert a protective role. CONCLUSIONS: HOMA-IR was an independent risk factor for increased CVR in MetS patients. Moreover, HOMA-IR elevates the risk of CVD regardless of MetS and thus can be used for screening the general population. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry (Registration Number: ChiCTR2100054654).

One-year outcomes of a novel venous stent for symptomatic iliofemoral venous obstruction: prospective cohort study.

BACKGROUND: A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. METHODS: Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. RESULTS: Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14-4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93-95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (- 4.30 ± 3.66) and 12 months (- 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001). CONCLUSIONS: The 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.

Identifying acute mesenteric ischemia via mesenteric fractional flow reserve in patients with spontaneous isolated superior mesenteric artery dissection: case report.

There is no definitive approach for assessing mesenteric ischemia and determining the optimal timing for endovascular intervention in the management of spontaneous isolated dissection of the superior mesenteric artery (SISMAD). A 56-year-old male with acute abdominal pain was diagnosed with SISMAD. After evaluating mesenteric ischemia through mesenteric fractional flow reserve (FFR), FFR was 0.72, and the patient was recommended conservative treatment for SISMAD, which involves fasting, total parenteral nutrition, and anticoagulation. The patient's syndrome was relieved after conservative treatment for 14 days without stent implantation. Over the next 5 years, no recurrence of abdominal pain or worsening of SISMAD was observed in the patient. Assessing the severity of mesenteric ischemia can be done through mesenteric FFR. Upon confirmation of the exclusion of risks related to dilatation or rupture of SISMAD aneurysm, an approach in favor of conservative management for SISMAD may indeed be considered pragmatic when the FFR exceeds 0.72.

Medical treatments for abdominal aortic aneurysm: an overview of clinical trials.

INTRODUCTION: Abdominal aortic aneurysm is a progressive, segmental, abdominal aortic dilation associated with a high mortality rate. Abdominal aortic aneurysms with diameters larger than 55 mm are associated with a high risk of rupture, and the most effective treatment options are surgical repair. Close observation and lifestyle adjustments are recommended for smaller abdominal aortic aneurysms with lower rupture risk. The development of medical therapies that limit or prevent the progression, expansion, and eventual rupture of abdominal aortic aneurysms remains an unmet clinical need. AREAS COVERED: This review provides an overview of completed and ongoing clinical trials examining the efficacies of various drug classes, including antibiotics, antihypertensive drugs, hypolipidemic drugs, hypoglycemic drugs, and other potential therapies for abdominal aortic aneurysms. A search of PubMed, Web of Science, Clinical Trials, and another six clinical trial registries was conducted in January 2024. EXPERT OPINION: None of the drugs have enough evidence to indicate that they can effectively inhibit the dilation of abdominal aortic aneurysm. More clinical trial data is required to support the efficacy of propranolol. Future research should also explore different drug delivery mechanisms, such as nanoparticles, to elevate drug concentration at the aneurysm wall.

Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.

BACKGROUND: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. METHODS: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. RESULTS: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. CONCLUSIONS: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.

Tunable and fast-cured hyaluronic acid hydrogel inspired on catechol architecture for enhanced adhesion property.

Hyaluronic acid-based hydrogels have been broadly used in medical applications due to their remarkable properties such as biocompatibility, biodegradability, super hydroscopicity, non-immunogenic effect, etc. However, the inherent weak and hydrophilic polysaccharide structure of pure hyaluronic acid (HA) hydrogels has limited their potential use in muco-adhesiveness, wound dressing, and 3D printing. In this research, we developed in-situ forming of catechol-modified HA hydrogels with improved mechanical properties involving blue-light curing crosslinking reaction. The effect of catechol structure on the physicochemical properties of HA hydrogels was evaluated by varying the content (0-40 %). The as-synthesized hydrogel demonstrated rapid prototyping, excellent wetting adhesiveness, and good biocompatibility. Furthermore, an optimized hydrogel precursor solution was used as a blue light-cured bio-ink with high efficiency and good precision and successfully prototyped a microstructure that mimicked the human hepatic lobule by using DLP 3D printing method. This catechol-modified HA hydrogel with tunable physicochemical and rapid prototyping properties has excellent potential in biomedical engineering.

Internal loading regulates the phosphorus concentration in a diversion input shallow lake in the semi-humid region of North China: Differentiated processes in littoral wetland and open water areas.

Diversion input lakes usually have a low catchment area/lake area ratio and pulsing pollution input. Various pollutants might accumulate in the lake continuously owing to the concentration effect under high evaporation but low precipitation over the entire area, typically for sedimentary cyclic elements such as phosphorus (P). However, the detailed transportation, sedimentation, and internal release mechanisms of P in the diversion input lakes remain unclear. This study conducted a year-long investigation of the littoral wetlands and open water areas of the shallow Lake Hengshui in the semi-humid region of North China. Results revealed that the average total P concentrations in the water and surficial sediment reached as high as 0.202 mg L-1 and 878.21 mg kg-1 in summer. The high water P levels in the lake were mainly regulated by the high internal P loading during summer and autumn, with the internal P loading being approximately nine times the external P loading. The littoral wetland area serves as a higher sedimentation sink and release source of P than the open water area. The concentrated P was continuously transported to the littoral wetland area through detritus burial, coprecipitation, and deposition of suspended particles. The release of P was mainly controlled by the dissolution of redox-sensitive Fe-P and Org-P at high temperatures and organic matter mineralization in the sediment, accompanied by the potential release capacity of apatite P (Ca-P). Future management of eutrophication and P levels in similar diversion input lakes should pay more attention to the high internal P loading in the sediment and the differentiated sedimentation and release processes in the littoral wetland and open water areas.

NADPH and NAC synergistically inhibits chronic ocular hypertension-induced neurodegeneration and neuroinflammation through regulating p38/MAPK pathway and peroxidation.

Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by neurodegeneration and neuroinflammation with retinal NAD/NADP and GSH decline. Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADP) and glutathione (GSH) are two redox reducers in neuronal and glial metabolism. However, therapeutic strategies targeting NAD/NADP or GSH do not exert ideal effects, and the underlying mechanisms are still poorly understood. We assessed morphological changes in retinal ganglion cells (RGCs), the affected neurons in glaucoma, and Müller cells, the major glial cells in the retina, as well as the levels of phosphorylated p38 (p-p38) and Caspase-3 in glaucoma patients. We constructed a modified chronic ocular hypertensive rat model and an oxygen-glucose deprivation (OGD) cell model. After applying NADPH and N-acetylcysteine (NAC), a precursor to cysteine, the rate-limiting substrate in GSH biosynthesis, to cells, apoptosis, axonal damage and peroxidation were reduced in the RGCs of the NAC group and p-p38 levels were decreased in the RGCs of the NADPH group, while in stimulated Müller cells cultured individually or cocultured with RGCs, gliosis and p38/MAPK, rather than JNK/MAPK, activation were inhibited. The results were more synergistic in the rat model, where either NADPH or NAC showed crossover effects on inhibiting peroxidation and p38/MAPK pathway activation. Moreover, the combination of NADPH and NAC ameliorated RGC electrophysiological function and prevented Müller cell gliosis to the greatest extent. These data illustrated conjoined mechanisms in glaucomatous RGC injury and Müller cell gliosis and suggested that NADPH and NAC collaborate as a neuroprotective and anti-inflammatory combination treatment for glaucoma and other underlying human neurodegenerative diseases.

Rescuing zinc anode-electrolyte interface: mechanisms, theoretical simulations and in situ characterizations.

The research interest in aqueous zinc-ion batteries (AZIBs) has been surging due to the advantages of safety, abundance, and high electrochemical performance. However, some technique issues, such as dendrites, hydrogen evolution reaction, and corrosion, severely prohibit the development of AZIBs in practical utilizations. The underlying mechanisms regarding electrochemical performance deterioration and structure degradation are too complex to understand, especially when it comes to zinc metal anode-electrolyte interface. Recently, theoretical simulations and in situ characterizations have played a crucial role in AZIBs and are exploited to guide the research on electrolyte engineering and solid electrolyte interphase. Herein, we present a comprehensive review of the current state of the fundamental mechanisms involved in the zinc plating/stripping process and underscore the importance of theoretical simulations and in situ characterizations in mechanism research. Finally, we summarize the challenges and opportunities for AZIBs in practical applications, especially as a stationary energy storage and conversion device in a smart grid.

Targeting Fatty Acid Desaturase I Inhibits Renal Cancer Growth Via ATF3-mediated ER Stress Response.

Monounsaturated fatty acids (MUFAs) play a pivotal role in maintaining endoplasmic reticulum (ER) homeostasis, an emerging hallmark of cancer. However, the role of polyunsaturated fatty acid (PUFAs) desaturation in persistent ER stress driven by oncogenic abnormalities remains elusive. Fatty Acid Desaturase 1 (FADS1) is a rate-limiting enzyme controlling the bioproduction of long-chain PUFAs. Our previous research has demonstrated the significant role of FADS1 in cancer survival, especially in kidney cancers. We explored the underlying mechanism in this study. We found that pharmacological inhibition or knockdown of the expression of FADS1 effectively inhibits renal cancer cell proliferation and induces cell cycle arrest. The stable knockdown of FADS1 also significantly inhibits tumor formation in vivo. Mechanistically, we show that while FADS1 inhibition induces ER stress, its expression is also augmented by ER-stress inducers. Notably, FADS1-inhibition sensitized cellular response to ER stress inducers, providing evidence of FADS1's role in modulating the ER stress response in cancer cells. We show that, while FADS1 inhibition-induced ER stress leads to activation of ATF3, ATF3-knockdown rescues the FADS1 inhibition-induced ER stress and cell growth suppression. In addition, FADS1 inhibition results in the impaired biosynthesis of nucleotides and decreases the level of UPD-N-Acetylglucosamine, a critical mediator of the unfolded protein response. Our findings suggest that PUFA desaturation is crucial for rescuing cancer cells from persistent ER stress, supporting FADS1 as a new therapeutic target.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

Interfacial Engineering of Zn Metal via a Localized Conjugated Layer for Highly Reversible Aqueous Zinc Ion Battery.

Aqueous zinc-ion batteries are regarded as promising and efficient energy storage systems owing to remarkable safety and satisfactory capacity. Nevertheless, the instability of zinc metal anodes, characterized by issues such as dendrite growth and parasitic side reactions, poses a significant barrier to widespread applications. Herein, we address this challenge by designing a localized conjugated structure comprising a cyclic polyacrylonitrile polymer (CPANZ), induced by a Zn2+-based Lewis acid (zinc trifluoromethylsulfonate) at a temperature of 120 °C. The CPANZ layer on the Zn anode, enriched with appropriate pyridine nitrogen-rich groups (conjugated cyclic -C=N-), exhibits a notable affinity for Zn2+ with ample deposition sites. This zincophilic skeleton not only serves as a protective layer to guide the deposition of Zn2+ but also functions as proton channel blocker, regulating the proton flux to mitigate the hydrogen evolution. Additionally, the strong adhesion strength of the CPANZ layer guarantees its sustained protection to the Zn metal during long-term cycling. As a result, the modified zinc electrode demonstrates long cycle life and high durability in both half-cell and pouch cells. These findings present a feasible approach to designing high performance aqueous anodes by introducing a localized conjugated layer.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

The intervention of cannabinoid receptor in chronic and acute kidney disease animal models: a systematic review and meta-analysis.

AIM: Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease. METHODS: PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE's RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury. RESULTS: The blockade or knockout of CB1 could significantly reduce blood urea nitrogen [SMD,- 1.67 (95% CI - 2.27 to - 1.07)], serum creatinine [SMD, - 1.88 (95% CI - 2.91 to - 0.85)], and albuminuria [SMD, - 1.60 (95% CI - 2.16 to - 1.04)] in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine [SMD, - 0.97 (95% CI - 1.83 to - 0.11)] and albuminuria [SMD, - 2.43 (95% CI - 4.63 to - 0.23)] in renal dysfunction animals compared with the control group. CONCLUSIONS: The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.

IRF5 governs macrophage adventitial infiltration to fuel abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.

Preoperative supine time for adrenal venous sampling: a prospective randomized controlled trial.

BACKGROUND: Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17-23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking. METHODS/DESIGN: This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation). DISCUSSION: P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.

Stabilizing Anode-Electrolyte Interface for Dendrite-Free Zn-Ion Batteries Through Orientational Plating with Zinc Aspartate Additive.

The stability of aqueous Zn-ion batteries (AZIBs) is detrimentally influenced by the formation of Zn dendrites and the occurrence of parasitic side reactions at the Zn metal anode (ZMA)-electrolyte interface. The strategic manipulation of the preferential crystal orientation during Zn2+ plating serves as an essential approach to mitigate this issue. Here, Zn aspartate (Zn-Asp), an electrolyte additive for AZIBs, is introduced not only to optimize the solvation structure of Zn2+ , but also to crucially promote preferential Zn2+ plating on the (002) crystal plane of ZMA. As a result, both side reactions and Zn dendrites are effectively inhibited, ensuring an anode surface free of both dendrites and by-products. The implementation of Zn-Asp leads to significant enhancements in both Zn||Zn symmetric and Zn||Ti batteries, which demonstrate robust cyclability of over 3200 h and high Coulombic efficiency of 99.29%, respectively. Additionally, the Zn||NaV3 O8 ·1.5H2 O full battery exhibits remarkable rate capability, realizing a high capacity of 240.77 mA h g-1 at 5 A g-1 , and retains 92.7% of its initial capacity after 1000 cycles. This research underscores the vital role of electrolyte additives in regulating the preferential crystal orientation of ZMA, thereby contributing to the development of high-performing AZIBs.

Comprehensive bioinformatics analysis revealed potential key genes and pathways underlying abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a permanent, asymptomatic segmental dilatation of the abdominal aorta, with a high mortality risk upon rupture. Identification of potential key genes and pathways may help to develop curative drugs for AAA. We conducted RNA-seq on abdominal aortic tissues from both AAA patients and normal individuals as a control group. Integrated bioinformatic analysis was subsequently performed to comprehensively reveal potential key genes and pathways. A total of 1148 differential expressed genes (DEGs) (631 up-regulated and 517 down-regulated) were identified in our study. Gene Ontology (GO) analysis revealed enrichment in terms related to extracellular matrix organization, while KEGG analysis indicated enrichment in hematopoietic cell lineage and ECM-receptor interaction. Protein-protein interaction (PPI) network analysis revealed several candidate key genes, and differential expression of 6 key genes (CXCL8, CCL2, PTGS2, SELL, CCR7, and CXCL1) was validated by Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic curve (ROC) analysis demonstrated these genes' high discriminatory ability between AAA and normal tissues. Immunohistochemistry indicated that several key genes were highly expressed in AAA tissues. Single-cell RNA sequencing revealed differential distribution patterns of these identified key genes among various cell types. 26 potential drugs linked to our key genes were found through DGIdb. Overall, our study provides a comprehensive evaluation of potential key genes and pathways in AAA, which could pave the way for the development of curative pharmacological therapies.

Gastrointestinal adverse events of tirzepatide in the treatment of type 2 diabetes mellitus: A meta-analysis and trials sequential analysis.

BACKGROUND: Tirzepatide (TZP) is a novel drug for type 2 diabetes mellitus (T2DM), but the gastrointestinal (GI) adverse events (AEs) is a limiting factor in clinical application. Therefore, this study systematically evaluated the GI AEs of TZP for T2DM. METHODS: Clinical trials of TZP for T2DM were retrieved from eight databases published only from the establishment of the database to February 2023. Revman5.3 and TSA0.9.5.10 Beta were used for meta-analysis and trials sequential analysis (TSA). RESULTS: Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05). TSA showed that the differences in total GI AEs, nausea, decreased appetite and constipation were conclusive. Compared with insulin, nausea, diarrhea, vomiting and decreased appetite were significantly increased in all doses of TZP (P < .05), and dyspepsia was significantly increased with TZP 15 mg (P < .05). TSA showed that these differences were all conclusive. Compared with GLP-1 RA, decreased appetite was significantly higher with TZP 5 mg, total GI AEs, decreased appetite and diarrhea were significantly higher with TZP 10 mg (P < .05), while nausea, vomiting, dyspepsia and constipation were significantly different in all dose groups, abdominal pain were not significantly different (P < .05) and TSA showed no conclusive results in this group. CONCLUSION: The GI AEs of TZP were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA. Nausea, diarrhea and decreased appetite are very common GI AEs of TZP, and the incidence is positively correlated with dose. GI AEs of TZP decrease gradually over time, so long-term steady medication may be expected to reduce GI AEs.

Analysis of potential biomarkers for diabetic kidney disease based on single-cell RNA-sequencing integrated with a single-cell sequencing assay for transposase-accessible chromatin.

Diabetic kidney disease (DKD) is a renal microvascular disease caused by hyperglycemia that involves metabolic remodeling, oxidative stress, inflammation, and other factors. The mechanism is complex and not fully unraveled. We performed an integrated single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) analyses of kidneys from db/db and db/m mice to identify differential open chromatin regions and gene expression, particularly in genes related to proximal tubular reabsorption and secretion. We identified 9,776 differentially expressed genes (DEGs) and 884 cell type-specific transcription factors (TFs) across 15 cell types. Glucose and lipid transporters, and TFs related to the circadian rhythm in the proximal tubules had significantly higher expression in db/db mice than in db/m mice (P<0.01). Crosstalk between podocytes and tubular cells in the proximal tubules was enhanced, and renal inflammation, oxidative stress, and fibrosis pathways were activated in db/db mice. Western blotting and immunohistochemical staining results showed that Wfdc2 expression in the urine and kidneys of DKD patients was higher than that in non-diabetic kidney disease (NDKD) controls. The revealed landscape of chromatin accessibility and transcriptional profiles in db/db mice provide insights into the pathological mechanism of DKD.