2D perfusion angiography: an alternative method to evaluate endovascular intervention for acute lower limb ischemia.

BACKGROUND: Despite advances in endovascular techniques to treat acute limb ischemia (ALI), evaluation of clinical outcomes for revascularization remains challenging, especially the accurate quantification of post-endovascular limb perfusion. This study aimed to investigate the accuracy and value of 2D perfusion angiography to evaluate endovascular intervention for ALI. METHODS: A total of 47 patients with ALI were retrospectively analyzed. The transcutaneous oxygen partial pressure (TcPO2) was obtained using laser Doppler blood perfusion monitoring. The ankle-brachial index (ABI) and angiographic images were obtained before and after endovascular intervention. iFlow imaging was used to obtain color-coded images. Regions of interest (ROIs) at the femoral head, knee joint, and ankle joint were selected to obtain the time to peak (TTP). The differences in the TTP between the knee and femoral head regions (TTP difference in the knee area) and between the ankle and knee regions (TTP difference in the ankle area) were observed. The TTP, ABI, and TcPO2 between the complete response (CR), partial response (PR), no response (NR), and amputation (AM) groups were compared. The correlation between TTP changes in the ankle area (ΔTTP) and changes in ABI (ΔABI)/changes in TcPO2 (ΔTcPO2) was analyzed. RESULTS: There was a significant increase in both TcPO2 and ABI compared with the pre-intervention values (27.75 ± 5.32 vs 40.92 ± 4.62, and 0.35 ± 0.16 vs 0.79 ± 0.15, respectively, all p < 0.01). The post-intervention TTP differences in the knee areas (5.12 ± 2.45 s) and ankle areas (6.93 ± 4.37 s) were significantly faster than pre-intervention TTP differences (7.03 ± 2.57 s and 10.66 ± 4.07 s, respectively, all p < 0.05). The post-operative TTP in the ankle area, post-operative TTP difference in the ankle area, and ΔTTP in the AM group were higher than the values in the CR and PR groups. The ΔTTP demonstrated strong correlation with ΔABI (r = -0.722, p < 0.01) and ΔTcPO2 (r = -0.734, p < 0.01). CONCLUSIONS: 2D perfusion angiography with enhanced visual and quantitative analysis exhibits great potential to evaluate the efficacy of endovascular intervention, and provides a quantitative and sensitive tool to evaluate post-endovascular limb perfusion for ALI patients.

Hepatic arterial infusion chemotherapy and sequential ablation treatment in large hepatocellular carcinoma.

AIM: To investigate the individualized survival benefit of hepatic arterial infusion chemotherapy (HAIC) and sequential ablation treatment in large hepatocellular carcinoma (HCC) patients. METHODS: Between February 2016 and December 2020, a total of 228 HCC patients (diameter > 5 cm) who underwent HAIC alone (HAIC group, n = 135) or HAIC and sequential ablation (HAIC-ablation group, n = 93) treatment were reviewed. We applied the inverse probability of treatment weighting (IPTW) to adjust for potential bias of two treatment groups. The overall survival (OS) and progression-free survival (PFS) were compared with Kaplan-Meier curves. The Cox regression model was used to identify independent prognostic factors. And a prediction nomogram based on these independent prognostic factors was built, aiming to make probabilistic survival predictions and estimate personalized ablation benefits. RESULTS: After a median follow-up of 17.9 months, HCC patients in the HAIC-ablation group have longer significantly OS and PFS than those in the HAIC alone group (median OS: 22.2 months vs. 14.5 months; median PFS: 8.5 months vs. 4.6 months; both, p < 0.001). The IPTW-adjusted analysis revealed similar findings (both, p < 0.001). Tumor size, tumor number, and treatment modality were identified as independent prognostic factors for OS. The nomogram based on these factors showed favorable discrimination and well calibration. CONCLUSIONS: HAIC and sequential ablation provided significant survival benefits in patients with large HCC. The nomogram could help predict individual survival probabilities and estimate personalized sequential ablation benefits.

The Ameliorative Effect of COST on Diet-Induced Lipid Metabolism Disorders by Regulating Intestinal Microbiota.

BACKGROUND: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders. METHODS: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation. CONCLUSIONS: intestinal microbiota plays a key role in COST inhibition of lipid metabolism disorder induced by a high fat and high sugar diet. In particular, COST may play a central regulatory role in microbiota, including Bacteroides, Akkermansia, and Desulfovibrio. Taken together, our work suggests that COST may improve the composition of gut microbes, increase the abundance of beneficial bacteria, improve lipid metabolism disorders, and inhibit the development of metabolic disorders.

The Microstructure, Antibacterial and Antitumor Activities of Chitosan Oligosaccharides and Derivatives.

Chitosan obtained from abundant marine resources has been proven to have a variety of biological activities. However, due to its poor water solubility, chitosan application is limited, and the degradation products of chitosan oligosaccharides are better than chitosan regarding performance. Chitosan oligosaccharides have two kinds of active groups, amino and hydroxyl groups, which can form a variety of derivatives, and the properties of these derivatives can be further improved. In this review, the key structures of chitosan oligosaccharides and recent studies on chitosan oligosaccharide derivatives, including their synthesis methods, are described. Finally, the antimicrobial and antitumor applications of chitosan oligosaccharides and their derivatives are discussed.

Identification of novel genetic variants for type 2 diabetes, childhood obesity, and their pleiotropic loci.

Obesity has result in increased prevalence of type 2 diabetes (T2D) in children. The genetic mechanisms underlying their relationship, however, are not fully understood. Here, we aim to identify novel SNPs associated with T2D and childhood obesity (CO), especially their pleiotropic loci. We integrated the summary statistics for two independent GWASs of T2D (n = 149,821) and childhood body mass index (CBMI) (n = 35,668) using the pleiotropy-informed conditional false discovery rate (cFDR) method. By leveraging the information of different levels of association for CBMI, we observed a strong enrichment of genetic variants associated with T2D. We identified 139 T2D-associated SNPs with 125 novel ones (cFDR < 0.05). Conditioned on T2D, we identified 37 significant SNPs for CBMI (cFDR < 0.05), including 25 novel ones. The conjunctional cFDR (ccFDR) analysis showed ten novel pleiotropic loci for T2D and CBMI (ccFDR < 0.05). Interestingly, the novel SNP rs1996023 is located at protein coding gene GNPDA2 (ccFDR = 1.28E-02), which has been reported to influence the risk of T2D and CO through central nervous system. Our findings may help to explain a greater proportion of the heritability for human traits and advance the understanding of the common pathophysiology between T2D and CO.

Perfusion imaging with 320-slice spiral computed tomography and color-coded digital subtraction angiography for assessing acute skeletal muscle ischemia-reperfusion injury in a rabbit model.

BACKGROUND: In recent years, skeletal muscle-related ischemia-reperfusion injury (IRI) has become more common. IRI can lead to severe limb injuries, multiple organ failure, and even death in some cases. However, there is still a lack of rapid and sensitive detection methods for IRI in skeletal muscle. This study aims to explore the value of computed tomography perfusion imaging (CTPI) and color-coded digital subtraction angiography (DSA) in assessing acute IRI of skeletal muscle in a rabbit model. METHODS: Fifty New Zealand white rabbits were randomly assigned to the ischemia-reperfusion (IR) group (n = 40) or sham group (n = 10). After 3 h of surgically-induced hindlimb ischemia, the IR group underwent reperfusion and CTPI and color-coded DSA were taken to assess the skeletal muscle at 0, 6, 12, or 24 h post-reperfusion. The data from CTPI and DSA in the right and left hindlimbs, blood flow (AF-R/L), blood volume (BV-R/L), contrast clearance rate (C-R/L) and the maximum contrast enhancement values (peak-R/L) were obtained. Serum superoxide dismutase (SOD), creatine kinase (CK), lactic dehydrogenase (LDH) and malondialdehyde (MDA) were measured. The statistical correlation between the above parameters (CTPI, color-coded DSA, and biochemical markers) was analyzed. RESULTS: The mean value of AF-R/L, BV-R/L, C-R/L and peak-R/L decreased linearly from 1.07 ± 0.08 to 0.75 ± 0.11, 1.03 ± 0.06 to 0.85 ± 0.14, 0.93 ± 0.15 to 0.71 ± 0.18, and 1.07 ± 0.01 to 0.47 ± 0.04, respectively. The correlation coefficients between AF-R/L and SOD, CK, LDH and MDA were 0.57, - 0.44, - 0.60, and - 0.62, respectively (p < 0.001). The correlation coefficients between Peak-R/L and SOD, CK, LDH, MDA were 0.59, 0.68, 0.71 and 0.66, respectively (p < 0.001). The correlation coefficient between AF-R/L and Peak-R/L was 0.70 (p < 0.001). CONCLUSION: Both CTPI and color-coded DSA could dynamically assess skeletal muscle IRI in rabbits.

Microplastics as an emerging vector of Cr(VI) in water: Correlation of aging properties and adsorption behavior.

Microplastics (MPs) are emerging contaminants with growing concerns due to their potential adverse effects on the environment. However, understanding the aging properties and adsorption behavior of MPs is still limited. In this study, we investigated the correlation between the adsorption capacity, aging stages, and aging properties of polyethylene MPs using a correlation equation. Our results revealed that the trends of O/C ratio and contact angle of polyethylene MPs with aging time were fitted to be linear under xenon lamp accelerated aging conditions. Conversely, the trends of other properties such as particle size, crystallinity, and molecular weight with time were fitted to conform to the Boltzmann equation. Moreover, the aging curve data for carbonyl index and molecular weight (Mw) perfectly matched, confirming Mw play a crucial role in verifying the aging process. Additionally, the adsorption amount of polyethylene MPs increased sharply with the increase of aging ages, reaching up to 1.850 mg/g. The adsorption data fit well to the pseudo-second-order kinetics and Langmuir model, suggesting that the adsorption process is dominated by chemisorption. The low pH and low salt concentration is beneficial to the adsorption capacity of MPs onto Cr(VI). Further, a relationship equation was established to predict adsorption risk at different aging stages. These findings provide new insights into the impact of aging on pollutants transport and the fate of MPs, enabling the prediction of adsorption risk of MPs at different aging stages in water environments.

Surface structures changes and biofilm communities development of degradable plastics during aging in coastal seawater.

Biodegradable plastics (BPs) are a suitable alternative to conventional plastics. Still, their excessive or unplanned use may disrupt the abundance and community structure of the microbial population. To this end, a 58-day experiment in which biodegradable plastic objects, such as bags and boxes, were exposed to near-coastal seawater was conducted. They also assessed how they affected the diversity and organization of bacterial populations in seawater and on the surface of BPs products. It is evident that after the exposure time, both BP's bag and box products deteriorate in the ocean to varying degrees. The results of high-throughput sequencing of bacterial communities in seawater and those colonized on BPs products reveal significant differences in microbial community structures between seawater and BPs plastic samples. These suggest that the degradation of biodegradable plastics is shadowed by microorganisms and exposure time, while BP products influence the structural characteristics of microbial communities.

Toxicity evaluation of silica nanoparticles for delivery applications.

Silica nanoparticles (SiNPs) are being explored as nanocarriers for therapeutics delivery, which can address a number of intrinsic drawbacks of therapeutics. To translate laboratory innovation into clinical application, their potential toxicity has been of great concern. This review attempts to comprehensively summarize the existing literature on the toxicity assessment of SiNPs. The current data suggest that the composition of SiNPs, their physicochemical properties, their administration route, their frequency and duration of administration, and the sex of animal models are related to their tissue and blood toxicity, immunotoxicity, and genotoxicity. However, the correlation between in vitro and in vivo toxicity has not been well established, mainly because both the in vitro and the in vivo-dosed quantities are unrealistic. This article also discusses important factors to consider in the toxicology of SiNPs and current approaches to reducing their toxicity. The aim is to give readers a better understanding of the toxicology of silica nanoparticles and to help identify key gaps in knowledge and techniques.

Clinical characteristics and acute complication of COVID-19 patients with diabetes: a multicenter, retrospective study in Southern China.

Aims: This study aims to describe the clinical characteristics, laboratory data and complications of hospitalized COVID-19 patients with type 2 diabetes mellitus (T2DM) since epidemic prevention and control optimization was adjusted in December 2022 in China. Methods: This retrospective multicenter study included 298 patients with confirmed type 2 diabetes mellitus with or without COVID-19. We collected data from the first wave of the pandemic in The Fifth Affiliated Hospital of Guangzhou Medical University, Loudi Central Hospital and The First People's Hospital of Xiangtan from December 1, 2022 to February 1, 2023. We extracted baseline data, clinical symptoms, acute complications, laboratory findings, treatment and outcome data of each patient from electronic medical records. Results: For among 298 hospitalized patients with type 2 diabetes, 136 (45.6%) were COVID-19 uninfected, and 162 (54.4%) were COVID-19 infected. We found that the incidence of cough, fatigue, fever, muscle soreness, sore throat, shortness of breath, hyposmia, hypogeusia and polyphagia (all p<0.01) were significantly higher in the exposure group. They showed higher levels of ketone (p=0.04), creatinine (p<0.01), blood potassium (p=0.01) and more diabetic ketoacidosis (p<0.01). Patients with COVID-19 less use of metformin (p<0.01), thiazolidinediones (p<0.01) and SGLT2 (p<0.01) compared with patients without COVID-19. Conclusion: COVID-19 patients with diabetes showed more severe respiratory and constitutional symptoms and an increased proportion of hyposmia and hypogeusia. Moreover, COVID-19 patients with diabetes have a higher incidence of acute complications, are more prone to worsening renal function, and are more cautious about the use of antidiabetic drugs.

The Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity.

Intestinal environment disorder is a potential pathological mechanism of obesity. There is increasing evidence that disorders in the homeostasis of the intestinal environment can affect various metabolic organs, such as fat and liver, and lead to metabolic diseases. However, there are few therapeutic approaches for obesity targeting the intestinal environment. In this review, on the one hand, we discuss how intestinal microbial metabolites SCFA regulate intestinal function to improve obesity and the possible mechanisms and pathways related to obesity-related pathological processes (depending on SCFA-related receptors such as GPCRs, MCT and SMCT, and through epigenetic processes). On the other hand, we discuss dietary management strategies to enrich SCFA-producing bacteria and target specific SCFA-producing bacteria and whether fecal bacteria transplantation therapy to restore the composition of the gut microbiota to regulate SCFA can help prevent or improve obesity. Finally, we believe that it will be of great significance to establish a working model of gut- SCFA- metabolic disease development in the future for the improvement this human health concern.

A new perspective on NAFLD: Focusing on the crosstalk between peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR).

Nonalcoholic fatty liver disease (NAFLD) is primarily caused by abnormal lipid metabolism and the accumulation of triglycerides in the liver. NAFLD is also associated with hepatic steatosis and nutritional and energy imbalances and is a chronic liver disease associated with a number of factors. Nuclear receptors play a key role in balancing energy and nutrient metabolism, and the peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR) regulate lipid metabolism genes, controlling hepatocyte lipid utilization and regulating bile acid (BA) synthesis and transport. They play an important role in lipid metabolism and BA homeostasis. At present, PPARα and FXR are the most promising targets for the treatment of NAFLD among nuclear receptors. This review focuses on the crosstalk mechanisms and transcriptional regulation of PPARα and FXR in the pathogenesis of NAFLD and summarizes PPARα and FXR drugs in clinical trials, laying a theoretical foundation for the targeted treatment of NAFLD and the development of novel therapeutic strategies.

Predictive value of baseline metabolic tumor burden on 18F-FDG PET/CT for brain metastases in patients with locally advanced non-small-cell lung cancer.

Objectives: Brain metastases (BMs) are a major cause leading to the failure of treatment management for non-small-cell lung cancer (NSCLC) patients. The purpose of this study was to evaluate the predictive value of baseline metabolic tumor burden on 18F-FDG PET/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for brain metastases (BMs) development in patients with locally advanced non-small-cell lung cancer (NSCLC) after treatment. Methods: Forty-seven patients with stage IIB-IIIC NSCLC who underwent baseline 18F-FDG PET/CT examinations were retrospectively reviewed. The maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor (SUVmaxT, MTVT, and TLGT), metastatic lymph nodes (SUVmaxN, MTVN, and TLGN), and whole-body tumors (SUVmaxWB, MTVWB, and TLGWB) were measured. The optimal cut-off values of PET parameters to predict brain metastasis-free survival were obtained using Receiver operating characteristic (ROC) analysis, and the predictive value of clinical variables and PET parameters were evaluated using Cox proportional hazards regression analysis. Results: The median follow-up duration was 25.0 months for surviving patients, and 13 patients (27.7%) developed BM. The optimal cut-off values were 21.1 mL and 150.0 g for MTVT and TLGT, 20.0, 10.9 mL and 55.6 g for SUVmaxN, MTVN and TLGN, and 27.9, 27.4 mL and 161.0 g for SUVmaxWB, MTVWB and TLGWB, respectively. In the Cox proportional hazards models, the risk of BM was significantly associated with MTVN and MTVWB or TLGN and TLGWB after adjusting for histological cell type, N stage, SUVmaxN, and SUVmaxWB. Conclusions: Baseline metabolic tumor burden (MTV and TLG) evaluated from the level of metastatic lymph nodes and whole-body tumors are significant predictive factors for BM development in patients with locally advanced NSCLC.

Daily versus three-times-weekly azithromycin in Chinese patients with non-cystic fibrosis bronchiectasis: protocol for a prospective, open-label and randomised controlled trial.

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) brought a heavy healthcare burden worldwide. Macrolide maintenance therapy was proved to be helpful in reducing exacerbation of NCFB. However, the optimal dosing regimens of macrolides have not been determined, and its efficacy in Chinese NCFB population has not been validated. This protocol describes a head-to-head clinical trial designed to compare the efficacy of two dosing regimens of azithromycin in Chinese NCFB population. METHODS AND ANALYSIS: This prospective, open-label and randomised controlled trial will be conducted in the First People's Hospital of Jiashan, China. Eligible patients with high-resolution CT defined NCFB will be randomly divided into three groups, which will receive either 250 mg daily azithromycin, or 500 mg three-times-weekly azithromycin or no treatment for 6 months. They will be followed up for another 6 months without treatment. The primary outcome is the mean rate of protocol-defined pulmonary exacerbation at 6 months. ETHICS AND DISSEMINATION: Ethical approval was obtained from the First People's Hospital of Jiashan Ethics Committee. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100052906.

Adsorption-desorption behavior of methylene blue onto aged polyethylene microplastics in aqueous environments.

In this study, polyethylene microplastics were artificially photoaged by xenon light. Experiments were then performed with methylene blue (MB) dye to compare the changes in the structure, properties, and adsorption-desorption behaviors of the aged and virgin polyethylene microplastics. The results showed that the aged polyethylene microplastics were hydrophilic with oxygen-containing functional groups, which enhanced the adsorption capacity of polyethylene for MB from 0.63 mg·g-1 to 8.12 mg·g-1. The adsorption isotherms changed from the Henry model (virgin polyethylene microplastics) to the Langmuir model (aged polyethylene microplastics), indicating that the partitioning function was gradually replaced by a single-layer covering during the adsorption process. In addition, 7% and 17.8% of the MB loaded onto the aged polyethylene microplastics was desorbed into water and a simulated intestinal fluid, respectively. These findings reveal that aged polyethylene microplastics can accumulate MB, thus posing potential risks to aqueous environments and biological tissues.

Application of relay puncture technique in treating patients with complicated lower extremity arterial diseases.

OBJECTIVE: This study aimed to introduce and evaluate the safety and efficacy of the relay puncture technique in patients with complicated lower extremity arterial diseases. METHODS: A total of 21 patients (16 male and five female patients; median age: 68.5 years old), who had suffered from lower extremity arterial diseases between December 2014 and July 2017, were retrospectively collected. For all patients, the contralateral femoral artery was not available for puncture access, and the length of the devices was too short for the brachial artery approach. Therefore, the relay puncture technique, in which the first puncture was performed on the brachial artery, followed by an antegrade puncture on the femoral artery, was used to accomplish the endovascular therapy. Percutaneous transluminal angioplasty and/or percutaneous transluminal stenting were/was used to assess the efficacy of the relay puncture technique. The ankle-brachial index (ABI) and Rutherford clinical classification were used to evaluate the improvement of symptoms after treatment. Patients were followed up for 1, 3, 6, and 12 months, and annually (mean: 16.6 months) after discharge. RESULTS: The relay puncture treatment had a 100% technical success rate, and immediately decreased the ischemic symptoms of patients after the procedure. The ABI significantly increased from 0.33 ± 0.18 to 0.75 ± 0.21 at the 1-year follow-up time point (P < 0.05). No serious complications occurred during the follow-up period. The 1-year primary patency rate was 71.43%. CONCLUSION: The relay puncture technique is a feasible technique in the hands of experienced and skilled equipment operators for the treatment of lower extremity arterial diseases, when the contralateral femoral artery is not available for puncture, and the length of the device is too short to treat the distal lesion of the femoral artery and popliteal artery through the brachial artery approach.