Association of prognostic nutritional index with peripheral artery disease in US adults: a cross-sectional study.

BACKGROUND: The objective of this study was to investigate the relationship between the prognostic nutritional index (PNI) and peripheral artery disease (PAD). METHODS: The present study is a cross-sectional study based on the National Health and Nutrition Survey (1999-2004). The laboratory-calculated PNI was divided into four groups based on quartiles(Q1:PNI ≤ 50.00; Q2: 50.01-53.00; Q3:53.01-56.00; Q4: > 56.00). PAD was defined as an ankle brachial pressure index (ABPI) ≤ 0.9 on the left or right. The relationship between PNI and PAD was examined using multifactor weighted logistic regression analysis, as well as subgroup analysis. Subgroup analyses were conducted based on demographic and clinical variables. RESULTS: A total of 5,447 individuals were included in our final analysis. The age of the participants was 59.56 ± 13.10 years, and males accounted for 52.8% (n = 2820). The prevalence of PAD was 6.7% (n = 363). After adjusting for all factors, participants with Q1 still had an increased risk of PAD, with an OR value of 1.593 and a 95% CI of 1.232-1.991. Subgroup analysis showed no significant interaction among multiple factors. CONCLUSIONS: In summary, we report that lower PNI are associated with a higher risk of PAD in US adults. It is hoped that this discovery can provide a reference for the prevention of PAD.

Safety and Efficacy of Excimer Laser Atherectomy Combined with a Drug-Coated Balloon in De Novo Femoral Popliteal Artery Disease: A Retrospective Study.

BACKGROUND: The effectiveness of excimer laser atherectomy (ELA) combined with drug-coated balloon (DCB) for de novo femoropopliteal artery disease (FPAD) is currently unknown. This case series evaluated the clinical outcomes of ELA combined with DCB in de novo FPAD from a real-world clinical perspective. METHODS: We conducted a retrospective study of patients treated with ELA + DCB for de novo FPAD between November 2016 and January 2020. The primary efficacy endpoint was the initial patency rate; secondary endpoints included target lesion revascularization without clinically driven target lesion revascularization (CD-TLR) and technical success. Primary safety endpoints included all-cause death, unplanned major amputation, and postoperative complications. RESULTS: The mean follow-up was 37.8 ± 25.3 months and included 56 consecutive patients (68.23 ± 8.01 years, 41 men). Forty-three patients had lifestyle-restricted claudication, and 13 patients had critical limb-threatening ischemia. The mean length of the lesion was 178.41 mm in all patients. The total lesion occlusion rate was 48.2 (n = 27), and the overall technical success rate was 100%. The 12-month, 24-month, 36-month, and 48-month primary patency rates of the ELA + DCB group were 75%, 66.1%, 58.9%, and 42.8%, respectively. Freedom from CD-TLR at 12, 24, 36, and 48 months was 83.9%, 80.3%, 76.8%, and 57.1%, respectively. CONCLUSIONS: In real-world clinical practice, ELA + DCB appears to be a safe and effective endovascular treatment for de novo FPAD, with a low rate of freedom from CD-TLR and a good patency rate.

The efficacy of atherectomy combined with percutaneous transluminal angioplasty (PTA)/drug-coated balloon (DCB) compared with PTA/DCB for infrapopliteal arterial diseases: A systematic review and meta-analysis.

OBJECTIVES: With the development of endovascular therapies, some studies have indicated a therapeutic potential for infrapopliteal arterial revascularization with atherectomy (AT). This study was designed to perform a meta-analysis to investigate the efficacy of AT combined with percutaneous transluminal angioplasty (PTA) or drug-coated balloon (DCB) compared with PTA or DCB for infrapopliteal arterial diseases. METHODS: This is a systematic review and meta-analysis. The Pubmed, Web of Science, and Cochrane Library were systematically searched for articles published up to November 2022, reporting using atherectomy devices for infrapopliteal arterial patients. Randomized controlled trials and retrospective studies were included, and clinical characteristic outcomes were extracted and pooled. Then, we analyzed the efficacies of the AT (AT + PTA or DCB) group and the non-AT (DCB or PTA) group for infrapopliteal arterial patients. RESULTS: We identified 6 studies with 1269 patients included in this meta-analysis. The risk ratios (RRs) of primary patency for patients treated with atherectomy group compared to non-atherectomy group at 6 months was 1.03 (95% confidence intervals (CIs) 0.86-1.23, p = .74), at 12 months was 1.05 (95% CIs 0.84-1.30, p = .66), in the subgroup analysis between AT combined with DCB and DCB alone, the RRs of primary patency was 1.56 (95% CIs 1.02-2.39, p = .04). The RRs of freedom from target lesion revascularization (TLR) at 6 months was 1.04 (95% CIs 0.93-1.17, p = .45), at 12 months was 1.20 (95% CIs 0.83-1.75, p = .33). The RRs of mortality at 6 months was 0.57 (95% CIs 0.29-1.11, p = .10), and at 12 months was 0.79 (95% CI 0.50-1.25, p = .31). The RRs of limb salvage at 12 months was 0.99 (95% CIs 0.92-1.07, p = .87). The standardized mean difference (SMD) of (Ankle-brachial index) ABI at 12 months was 0.16 (95% CIs 0.06-0.26, p = .001). CONCLUSIONS: According to this systematic review and meta-analysis, no significant advantages were found with the addition of atherectomy to balloon angioplasty in the below-the-knee segment. Only in the analysis of a small subgroup of atherectomy + DCB versus DCB alone was the primary patency rate at six months significantly higher when adding atherectomy. No further significant differences were found related to 12 months of primary patency, TLR, limb salvage, and mortality among groups.

Efficacy and Safety of Atherectomy Combined With Balloon Angioplasty vs Balloon Angioplasty Alone in Patients With Femoro-Popliteal Lesions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Balloon angioplasty (BA), including drug-coated balloons (DCBs) and percutaneous transluminal angioplasty (PTA), has traditionally been used to treat femoral-popliteal lesions. However, in recent years, atherectomy (ATH) has been proposed as a complementary approach. To assess the effectiveness of ATH compared with BA alone in patients with femoral-popliteal artery lesions, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We included RCTs that focused on patients with femoral-popliteal artery lesions and reported data on the use of ATH and BA therapy. Two reviewers conducted a literature search, refined the data, and assessed the risk of bias. RESULTS: We included a total of 6 RCTs involving 399 patients with femoral-popliteal artery lesions. The use of ATH in combination with BA appeared to improve the patency rate at 12 months (odds ratio [OR]=2.04, 95% confidence interval [CI]=1.14-3.62). In addition, ATH with BA was associated with lower major amputation rates (MD=2.01, 95% CI=0.06-0.77, p=0.02) and a decreased likelihood of bailout stenting (OR=0.07, 95% CI=0.02-0.25, p=0.001). However, there were no statistically significant differences between the groups in terms of target lesion revascularization (TLR) at 12 months, major adverse cardiovascular events (MACEs), and distal embolization events. In addition, we performed subgroup analysis for different ATH devices and BA types. CONCLUSIONS: Based on this meta-analysis, it can be concluded that the use of ATH in combination with BA is a safe and effective method for treating femoral-popliteal artery lesions. In addition, the patency rate at 1 year is superior to treatment with BA alone. Atherectomy also reduces the likelihood of amputation and bailout stenting. Clinicians should consider these findings when designing future RCTs and developing clinical practice guidelines. CLINICAL IMPACT: This meta-analysis summarises a number of existing studies to advance understanding of the atherectomy devices and to reveal its potential. This new technique, when compared with drug coated balloon, shows the possibility of obtaining better clinical outcomes in femoro-popliteal lesions than drug-coated balloon alone, such as higher 12-month primary patency rates as shown in some studies. Currently, it is important to consider the appropriate technology applicable for individualised treatment. atherectomy devices seem to provide clinicians with additional options in clinical practice and to benefit patients in the future. This requires more high quality studies to explore the role and benefits of atherectomy devices in femoro-popliteal lesions.

Triphlorethol-A attenuates U251 human glioma cancer cell proliferation and ameliorates apoptosis through JAK2/STAT3 and p38 MAPK/ERK signaling pathways.

Glioma is the foremost recurrent type of brain tumor in humans; in particular, glioblastoma (GBM) is the main form of brain tumor (GBM) that is highly proliferative and impervious to apoptosis. Triphlorethol-A (TA), a phlorotannin isolated from Ecklonia cava, exhibited cytoprotective, antioxidant, and anticancer properties. However, the exact molecular action of TA in the U251 human GBM cells remains unknown. This may be the first report on the antiproliferative and apoptotic mechanisms of TA on GBM. The cytotoxicity, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), and cell apoptosis activity of TA have been evaluated by the MTT assay and by DCFH-DA, Rh-123, AO/EB, and western blot analysis. The results obtained showed that TA abridged the viability of U251 cells, while MMP increased apoptosis by increasing the ROS levels in a time-dependent manner. The results showed that a reduction in U251 cell proliferation was associated with the regulation of JAK2/STAT3 and p38 MAPK/ERK signaling pathways. TA was found to suppress pJAK, pSTAT3, p38 MAPK, and pERK phosphorylation, thereby causing Bax/Bcl-2 imbalance, activating the caspase cascade and cytochrome c, and inducing apoptosis. Our findings showed that the suppression of JAK2/STAT3 and p38 MAPK/ERK signaling by TA results in cell growth arrest and stimulation of apoptosis in GBM cells. These studies justify the protective remedy of TA against GBM.

Biological small-calibre tissue engineered blood vessels developed by electrospinning and in-body tissue architecture.

There are no suitable methods to develop the small-calibre tissue-engineered blood vessels (TEBVs) that can be widely used in the clinic. In this study, we developed a new method that combines electrospinning and in-body tissue architecture(iBTA) to develop small-calibre TEBVs. Electrospinning imparted mechanical properties to the TEBVs, and the iBTA imparted biological properties to the TEBVs. The hybrid fibres of PLCL (poly(L-lactic-co-ε-caprolactone) and PU (Polyurethane) were obtained by electrospinning, and the fibre scaffolds were then implanted subcutaneously in the abdominal area of the rabbit (as an in vivo bioreactor). The biotubes were harvested after four weeks. The mechanical properties of the biotubes were most similar to those of the native rabbit aorta. Biotubes and the PLCL/PU vascular scaffolds were implanted into the rabbit carotid artery. The biotube exhibited a better patency rate and certain remodelling ability in the rabbit model, which indicated the potential use of this hybridization method to develop small-calibre TEBVs. Sketch map of developing the biotube. The vascular scaffolds were prepared by electrospinning (A). Silicone tube was used as the core, and the vascular scaffold was used as the shell (B). The vascular scaffold and silicone tube were implanted subcutaneously in the abdominal area of the rabbit (C). The biotube was extruded from the silicone tube after 4 weeks ofembedding (D). The biotube was implanted for the rabbit carotid artery (E).

Identification of key genes and pathways involved in abdominal aortic aneurysm initiation and progression.

OBJECTIVE: The study aimed to assess the gene expression profile of biopsies obtained from the neck of human abdominal aortic aneurysm (AAA) and the main site of AAA dilatation and to investigate the molecular mechanism underlying the development of AAA. METHODS: The microarray profile of GSE47472 and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database. The GSE47472 was a microarray dataset of tissues from the aortic neck of AAA patients versus normal controls. The GSE57691 was a microarray dataset including the tissues from main site of AAA dilatation versus normal controls. Differentially expressed genes (DEGs) were chosen using the R package and annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). The hub genes were identified in the protein-protein interaction (PPI) network. RESULTS: 342 upregulated DEGs and 949 downregulated DEGs were obtained from GSE47472. The upregulated DEGs were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein binding (ontology: MF), and the downregulated genes were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein blinding (ontology: MF). In the KEGG enrichment analysis, the DEGs mainly involved glycosaminoglycan degradation, vasopressin-regulated water reabsorption, and pyruvate metabolism. The hub genes in GSE47472 mainly include VAMP8, PTPRC, DYNLL1, RPL38, RPS4X, HNRNPA1, PRMT1, TGOLN2, PA2G4, and CUL2. From GSE57691, 248 upregulated DEGs and 1120 downregulated DEGs were selected. The upregulated DEGs of GSE57691 were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein binding (ontology: MF), and the downregulated genes were mainly enriched in metabolic process (ontology: BP), the membrane (ontology: CC), and protein blinding (ontology: MF). In the KEGG enrichment analysis, the DEGs mainly involved the mitochondrial respiratory, respiratory chain complex, and respiratory chain. RPS15A, RPS5, RPL23, RPL27A, RPS24, RPL35A, RPS4X, RPL7, RPS25, and RPL21 were identified as the hub genes. CONCLUSION: At the early stage of AAA, the current study indicated the importance of glycosaminoglycan degradation and anaerobic metabolism. We also identified several hub genes closely related to AAA (VAMP8, PTPRC, DYNLL1, etc.). At the progression of the AAA, the dysfunctional mitochondria played a critical role in AAA formation and the RPS15A, RPS5, RPL23, etc., were identified as the hub genes.

Vanillin oxime inhibits lung cancer cell proliferation and activates apoptosis through JNK/ERK-CHOP pathway.

Lung cancer despite advancement in the medical field continues to be a major threat to human lives and accounts for a high proportion of fatalities caused by cancers globally. The current study investigated vanillin oxime, a derivative of vanillin, against lung cancer cells for development of treatment and explored the mechanism. Cell viability changes by vanillin oxime were measured using MTT assay. Vanillin oxime-mediated apoptosis was detected in A549 and NCI-H2170 cells at 48 h of exposure by flow cytometry. The CEBP homologous protein (CHOP) and death receptor 5 (DR5) levels were analysed by RT-PCR and protein levels by Western blotting. Vanillin oxime in concentration-dependent way suppressed A549 and NCI-H2170 cell viabilities. On exposure to 12.5 and 15 µM concentrations of vanillin oxime elevated Bax, caspase-3, and -9 levels in A549 and NCI-H2170 cells were observed. Vanillin oxime exposure suppressed levels of Bcl-2, survivin, Bcl-xL, cFLIP, and IAPs proteins in A549 and NCI-H2170 cells. It stimulated significant elevation in DR4 and DR5 levels in A549 and NCI-H2170 cells. In A549 and NCI-H2170 cells vanillin oxime exposure caused significant (p < 0.05) enhancement in CHOP and DR5 mRNA expression. Vanillin oxime exposure of A549 and NCI-H2170 cells led to significant (p < 0.05) enhancement in levels of phosphorylated extracellular-signal-regulated kinase and c-Jun N-terminal kinase. Thus, vanillin oxime inhibits pulmonary cell proliferation via induction of apoptosis through tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated pathway. Therefore, vanillin oxime may be studied further to develop a treatment for lung cancer.

Decellularized, Heparinized Small-Caliber Tissue-Engineered "Biological Tubes" for Allograft Vascular Grafts.

There remains a lack of small-caliber tissue-engineered blood vessels (TEBVs) with wide clinical use. Biotubes were developed by electrospinning and in-body tissue architecture (iBTA) technology to prepare small-caliber TEBVs with promising applications. Different ratios of hybrid fibers of poly(l-lactic-co-ε-caprolactone) (PLCL) and polyurethane (PU) were obtained by electrospinning, and the electrospun tubes were then implanted subcutaneously in the abdominal area of a rabbit (as an in vivo bioreactor). The biotubes were harvested after 4 weeks. They were then decellularized and cross-linked with heparin. PLCL/PU electrospun vascular tubes, decellularized biotubes (D-biotubes), and heparinized combined decellularized biotubes (H + D-biotubes) underwent carotid artery allograft transplantation in a rabbit model. Vascular ultrasound follow-up and histological observation revealed that the biotubes developed based on electrospinning and iBTA technology, after decellularization and heparinization cross-linking, showed a better patency rate, adequate mechanical properties, and remodeling ability in the rabbit model. IBTA technology caused a higher patency, and the heparinization cross-linking process gave the biotubes stronger mechanical properties.

Association of the controlling nutritional status score with all-cause mortality and cancer mortality risk in patients with type 2 diabetes: NHANES 1999-2018.

OBJECTIVE: There are studies on the nutritional status of type 2 diabetes (T2D), but there are no large cohort studies on the prognosis of Controlling Nutritional Status (CONUT) score for T2D. The aim of this study was to examine the association between CONUT score and all-cause mortality as well as cancer mortality in adults with T2D. METHODS: For this study, we analyzed a total of 3763 adult patients with T2D who were part of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Mortality outcomes were determined by linking to the National Death Index records as of December 31, 2019. Cox proportional risk models were used to estimate risk ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cancer deaths. RESULTS: During the mean follow-up of 8.17 years, there were 823 deaths from all causes and 155 deaths from cancer. After adjusting for multiple variables, the risk of all-cause mortality was higher in patients with a Mild (CONUT score ≥ 2), compared with patients with a Normal (CONUT score of 0-1). All-cause mortality risk was 39% higher, and cancer mortality risk was 45% higher. Consistent results were observed when stratified by age, sex, race, BMI, smoking status, and glycated hemoglobin levels. CONCLUSIONS: In a nationally representative sample of American adults with T2D, we found an association between CONUT score and all-cause mortality and cancer mortality.

Impact of geriatric nutritional risk index on prognosis in peripheral artery disease patients undergoing endovascular therapy.

The prevalence of peripheral artery disease continues to rise, with major amputations and mortality remaining prominent. Frailty is a significant risk factor for adverse outcomes in the management of the vascular disease. The geriatric nutritional risk index has been used to predict adverse outcomes in lower extremity peripheral artery disease and is a nutrition-based surrogate for frailty. The authors recruited 126 patients with peripheral artery disease who underwent endovascular stent implantation. As in previous reports, malnutrition was diagnosed by the geriatric nutritional risk index. The authors used Kaplan-Meier and multivariate Cox proportional hazards regression analyses to analyze the risk of major adverse limb events, which included mortality, major amputation, and target limb revascularization. There were 67 major adverse limb events during a median follow-up of 480 days. Malnutrition on the basis of the geriatric nutritional risk index was present in 31% of patients. Cox regression analysis showed that malnutrition based on the geriatric nutritional risk index was an independent predictor of major adverse limb events. Kaplan-Meier analysis showed that major adverse limb events increased with worsening malnutrition. Our single-center, retrospective evaluation of geriatric nutritional risk index (as a synonym for body health) correlates with an increased risk of major adverse limb events. Future directions should focus not only on identifying these patients but also on modifying risk factors to optimize long-term outcomes.

Association of prognostic nutritional index with the risk of all-cause mortality and cardiovascular mortality in patients with type 2 diabetes: NHANES 1999-2018.

INTRODUCTION: There is little bulk clinical evidence on nutritional status and mortality in patients with diabetes. The purpose of this study was to examine the relationship between prognostic nutritional index (PNI) and all-cause mortality and cardiovascular mortality in adults with diabetes. RESEARCH DESIGN AND METHODS: This study included 5916 adult patients with diabetes from the National Health and Nutrition Examination Survey 1999-2018. Cox proportional risk models were used to estimate risk ratios (HRs) and 95% CIs for all-cause mortality, cardiovascular disease (CVD) mortality. RESULTS: During a mean follow-up of 8.17 years, there were 1248 deaths from all causes and 370 deaths from CVD. After multivariate adjustment, the risk of all-cause mortality was reduced by 24%, 38%, and 28% in Q2 (49.0-52.99), Q3 (53.0-57.99), and Q4 (≥58.0), respectively, compared with Q1 (PNI<49.0). The risk of cardiovascular mortality was reduced by 30%, 27%, and 26%, respectively. Consistent results were observed in the subgroup analysis. CONCLUSIONS: Lower serum PNI levels were significantly associated with higher all-cause and CVD mortality. These findings suggest that maintaining an appropriate range of serum PNI status may reduce the risk of death in patients with diabetes.

Pharmacotherapy in Clinical Trials for Abdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis.

OBJECTIVE: There is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the efficacy of pharmacotherapy in limiting AAA growth and AAA-related events. METHODS: A systematic literature search was performed to examine the efficacy of pharmacotherapy in reducing AAA growth and AAA-related events. Pubmed, Embase (Excerpta Medica Database), and the Cochrane library were searched from March, 1999 to March 29, 2022. AAA growth (mm/year) in the intervention and control groups was expressed as mean and standard deviation (SD). The results of AAA growth were expressed as mean difference (MD) and its 95% confidence interval (95% CI). Odds ratios (ORs) were calculated for the AAA-related events.Heterogeneity was quantified using the I2 statistic. Forest plots were created to show the pooled results of each outcome. OUTCOMES: A total of 1373 articles were found in different databases according to the search strategy, and 10 articles were identified by hand searching. A total of 26 articles were included in our systematic review after the screening. For the studies of metformin, the meta-analysis demonstrated that metformin use was associated with a lower AAA growth rate (MD: -0.81 mm/y, 95% CI: -1.19 to -0.42, P < 0.0001, I2 = 87%), Metformin use also was related to the lower rates of AAA-related events (OR: 0.53, 95% CI: 0.36 to 0.76, P = 0.0007, I2 = 60%). The hypotensive drugs of the studies mainly included angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), and propranolol. The overall meta-analysis of blood pressure-lowering drugs reported no significant effect in limiting the AAA growth (MD: 0.31mm/year, 95%CI: -0.03 to 0.65, P = 0.07, I2 = 66%) and AAA-related events (OR: 1.33, 95%CI: 0.76 to 2.32, P = 0.32, I2 = 98%), In the subgroup analysis of the hypotensive drugs, the ACEI/ARB and propranolol also showed no significant in reducing the AAA growth and AAA-related events. The meta-analysis of the antibiotics demonstrated that the antibiotics were not associated with a lower AAA growth rate (MD: -0.27 mm/y, 95% CI: -0.88 to 0.34, P = 0.39, I2 = 77%) and AAA-related events (OR: 0.94, 95%CI: 0.65 to 1.35, P = 0.72, I2 = 0%). The results of statins also showed no significant effect in limiting AAA growth (MD: -1.11mm/year, 95%CI: -2.38 to 0.16, P = 0.09, I2 = 96%) and AAA-related events (OR: 0.53, 95%CI: 0.26 to 1.06, P = 0.07, I2 = 92%). CONCLUSION: In conclusion, effective pharmacotherapy for AAA was still lacking. Although the meta-analysis showed that metformin use was associated with lower AAA growth and AAA-related events, all of the included studies about metformin were cohort studies or case-control studies. More randomized controlled trials (RCTs) are needed for further verification.

Identification of hub genes and regulatory networks in histologically unstable carotid atherosclerotic plaque by bioinformatics analysis.

OBJECTIVE: This study identified underlying genetic molecules associated with histologically unstable carotid atherosclerotic plaques through bioinformatics analysis that may be potential biomarkers and therapeutic targets. METHODS: Three transcriptome datasets (GSE41571, GSE120521 and E-MTAB-2055) and one non-coding RNA dataset (GSE111794) that met histological grouping criteria of unstable plaque were downloaded. The common differentially expressed genes (co-DEGs) of unstable plaques identified from three mRNA datasets were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). A protein-protein interaction (PPI) network was constructed to present the interaction between co-DEGs and screen out hub genes. MiRNet database and GSE111794 dataset were used to identify the miRNAs targeting hub genes. Associated transcription factors (TFs) and drugs were also predicted. These predicted results were used to construct miRNA/TFs-hub gene and drug-hub gene regulatory networks. RESULTS: A total of 105 co-DEGs were identified, including 42 up-regulated genes and 63 down-regulated genes, which were mainly enriched in collagen-containing extracellular matrix, focal adhesion, actin filament bundle, chemokine signaling pathway and regulates of actin cytoskeleton. Ten hub genes (up-regulated: HCK, C1QC, CD14, FCER1G, LCP1 and RAC2; down-regulated: TPM1, MYH10, PLS3 and FMOD) were screened. HCK and RAC2 were involved in chemokine signaling pathway, MYH10 and RAC2 were involved in regulation of actin cytoskeleton. We also predicted 12 miRNAs, top5 TFs and 25 drugs targeting hub genes. In the miRNA/TF-hub gene regulatory network, PLS3 was the most connected hub genes and was targeted by six miRNAs and all five screened TFs. In the drug-hub gene regulatory network, HCK was targeted by 20 drugs including 10 inhibitors. CONCLUSIONS: We screened 10 hub genes and predicted miRNAs and TFs targeting them. These molecules may play a crucial role in the progression of histologically unstable carotid plaques and serve as potential biomarkers and therapeutic targets.

The efficacy and safety of different endovascular modalities for infrapopliteal arteries lesions: A network meta-analysis of randomized controlled trials.

Background: Endovascular treatment has become the first-line therapy for infrapopliteal artery occlusive disease (IPOD), while the optimal endovascular method remains to be determined. We performed a network meta-analysis (NWM) of randomized controlled trials (RCTs) to simultaneously compare the outcomes of different endovascular modalities for IPOD. Methods and results: The Pubmed, Embase, and Cochrane databases were used as data sources. The NWM approach used random-effects models based on the frequentist framework. In total, 22 eligible RCTs (44 study arms; 1,348 patients) involving nine endovascular modalities or combinations [balloon angioplasty (BA), drug-coated balloon (DCB), drug-eluting stent (DES), atherectomy device + BA (AD + BA), AD + DCB, balloon-expandable bare metal stent (BMS), self-expanding stent (SES), absorbable metal stents (AMS), and inorganics-coated stent (ICS)] were included. BA had a lower 12-month primary patency rate than DCB (RR 0.50, CI 0.27, 0.93) and AD + DCB (RR 0.34, CI 0.12, 0.93). AD + DCB decreased 6-month TLR compared with AMS (RR 0.15, CI 0.03, 0.90), and DES decreased it compared with BMS (RR 0.25, CI 0.09, 0.71). DCB had a lower 6-month TLR rate than AMS (RR 0.26, CI 0.08, 0.86) and BA (RR 0.51, CI 0.30, 0.89). BA had a higher 12-month TLR rate than DCB (RR 1.76, CI 1.07, 2.90). According to the value of the surface under the cumulative ranking curve (SUCRA), AD + DCB was considered the best treatment in terms of primary patency at 6 months (SUCRA = 87.5) and 12 months (SURCA = 91). AD + BA was considered the best treatment in terms of 6-month TLR (SUCRA = 83.1), 12-month TLR (SURCA = 75.8), and 12-month all-cause mortality (SUCRA = 92.5). In terms of 12-month major amputation, DES was considered the best treatment (SUCRA = 78.6), while AD + DCB was considered the worst treatment (SUCRA = 28.8). Moreover, AD + BA always ranks higher than AD + DCB in the comparison including these two combinations. Subgroup analyses of modalities without stenting did not significantly change the primary outcomes. Conclusion: ADs showed noteworthy advantages in multiple terms for IPOD except for 12-month major amputation. AD + BA may be a better method for IPOD than AD + DCB. The efficacy and safety of ADs are worthy of further investigation. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022331626].

Exosome-Mediated Transfer of Long Noncoding RNA HOTAIR Regulates Temozolomide Resistance by miR-519a-3p/RRM1 Axis in Glioblastoma.

Background: Chemoresistance obstructs the treatment of glioblastoma (GB). Exosome-mediated transfer of long noncoding RNAs (lncRNAs) was reported to regulate chemoresistance in diverse cancers. The authors aimed to investigate the underlying mechanism of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) in regulating temozolomide (TMZ) resistance in GB. Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to check TMZ resistance and cell proliferation. The abilities of cell migration and invasion were evaluated by transwell assay. The protein levels of E-cadherin, N-cadherin, Vimentin, CD63, CD81, and ribonucleoside-diphosphate reductase subunit M1 (RRM1) were measured by western blot. Quantitative real-time polymerase chain reaction was conducted to detect the levels of HOTAIR, microRNA (miR)-519a-3p, and RRM1. The starBase was hired to predict the target sites between miR-519a-3p and HOTAIR or RRM1 and the dual-luciferase reporter assay was performed to verify the interaction. Xenograft tumor model was established to investigate the biological role of HOTAIR in vivo. Results: The high abilities of cell viability and metastasis were observed in TMZ-resistant GB cells. LncRNA HOTAIR was significantly upregulated in TMZ-resistant GB cells and its downregulation inhibited proliferation, migration, invasion, and epithelial/mesenchymal transition in TMZ-resistant GB cells. Further analysis indicated that exosomal lncRNA HOTAIR induced TMZ resistance and modulated TMZ resistance through miR-519a-3p/RRM1 axis. Besides, serum exosomal lncRNA HOTAIR was stable and had diagnostic value. Moreover, knockdown of lncRNA HOTAIR reduced TMZ resistance in vivo. Conclusions: Exosomal lncRNA HOTAIR mediated TMZ resistance through miR-519a-3p/RRM1 axis in GB.

Unique twisted ribbons generated by self-assembly of oligo(p-phenylene ethylene) bearing dimeric bile acid pendant groups.

Let's twist again! Remarkable broad and twisted ribbons were generated from the self-assembly of oligo(p- phenylene ethylene) (OPE) bearing dimeric deoxycholic acid pendant groups (see graphic). Varying the bile acid led to nanostructures with drastically different morphologies. The distinctive aggregate shapes of these steroid-OPE conjugates are attributed to the subtle differences in their molecular structures.A series of novel oligo(p-phenylene ethynylene) (OPE) derivatives bearing dimeric cholic acid (OPE1), deoxycholic acid (OPE2) and lithocholic acid (OPE3) was synthesized. The self-assembly behavior of these derivatives were systematically studied and compared in a THF/water solvent mixture. The addition of water to THF can induce the helical stacking of oligo(p-phenylene ethylene) bearing dimeric deoxycholic acid end groups, which leads to highly interesting twisted assemblies. Variation of the bile acid group led to nanostructures with drastically different morphologies. The application of spectroscopy in combination with X-ray diffraction techniques provided a reasonable view of the final self-assembled structures. The observed distinctive aggregate shapes and the preference in the type of molecular packing of these steroid-OPE conjugates are attributed to the subtle differences in their molecular features.

Non-small cell lung cancer leptomeningeal metastases treated with intrathecal therapy plus osimertinib and temozolomide and whole-brain radiation therapy: a case report.

RATIONALE: Leptomeningeal metastasis (LM) is an important cause of mortality in patients with non-small cell lung cancer (NSCLC). As the symptoms of LM and its early clinical manifestations are nonspecific, early diagnosis of LM is difficult. However, there are few treatment options for LM, which leads to a poor prognosis; thus, increased clinical attention is necessary. The effects of most systemic chemotherapies on metastatic brain tumors (brain metastases and LMs) are limited as they cannot pass the blood-brain barrier; therefore, whole-brain radiation therapy is a therapeutic option. Osimertinib is a potent and irreversible third-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It binds to EGFR with high affinity when the EGFR T790M mutation is present together with sensitizing mutations. The clinical efficacy of osimertinib in NSCLC patients carrying the T790M mutation has been demonstrated in clinical trial NCT02468661. Intrathecal injection of chemotherapeutic drugs can be directed to a specific lesion. Temozolomide is one such drug, and its effect has been confirmed. PATIENT AND INTERVENTIONS: We treated a 38-year-old patient with NSCLC who carried the EGFR L858R mutation. We administered a combination of oral osimertinib and oral temozolomide plus an intrathecal injection of cytarabine and whole-brain radiation therapy for symptomatic multiple brain metastases. OUTCOMES: The patient showed a marked response to this combination therapy. To date (after ~18 months), no recurrence or new lesions have been observed and he is asymptomatic. His disease-free survival surpasses that achieved with any monotherapy for LM. LESSONS: This is the first report to demonstrate the response to combination therapy in an NSCLC patient with LM. These findings indicate the potential utility of chemotherapy combined with radiotherapy combined with targeted therapy combined with local treatment, as each treatment acts via a different mechanism, enhancing their therapeutic effects.

[Relationship between oxidative stress and depression in patients with acute leukemia].

This study was aimed to investigate the relationships between oxidative stress and depression in patients with acute leukemia. Ninety two cases of acute leukemia were randomly enrolled in the study. Depressive disorder was assessed by self-rating depression scales (SDS) and multiple items questionaires. The total anti-oxidation capability (T-AOC), reactive oxygen species (ROS) and superoxide dismutase (SOD) activities, as well as malondialdehyde (MDA) and nitric oxide (NO) levels were measured in pre-treatment periods. Meanwhile, the steady state level of human 8-hydroxyguanine glycosylase (hOGG1) mRNA transcript was monitored by quantitative real-time PCR. The results showed that the defence of antioxidant system was impaired in patients with acute leukemia. The incidence of depression was 47.83% in 92 cases. T-AOC and SOD activities were significantly decreased in patients with depression, while ROS, NO, MDA levels and hOGG1 mRNA expression were reverse of the former. It revealed that depression positively correlated with course of disease and hOGG1, and negatively correlated with T-AOC. It is concluded that oxidative damage occurs in patients with acute leukemia, moreover, lower antioxidant defences exist in depressive patients. These results underscore the notion that oxidative stress may promote the development of depression.