The regulation and its application of the charge decay rate in triboelectric nanogenerator.

The decay rate of charge in the friction layer is one of the key factors affecting the output performance of triboelectric nanogenerators (TENG). Reducing the decay rate of the triboelectric charge can increase the charge-carrying capacity of the friction layer and improve the output current and voltage of the TENG. This makes a friction generator more suitable for discontinuous driving environments. In contrast, increasing the decay rate of the charge in the friction layer can greatly improve the recovery time of the device, although it reduces the output performance of the generator. This is conducive to the application of friction generator in the field of sensors. In this study, polystyrene (PS) and carbon nanotubes (CNTs) were added to polyvinylidene fluoride (PVDF) nanofibers to adjust the charge decay time in the friction layer, thereby regulating the output performance of the friction generator and sensor. When the amount of added PS in the PVDF nanofiber reached 20%, the charge density on the friction surface increased by 1.9 times, and the charge decay time decreased by 64 times; when 0.1 wt% CNTs were added in the PVDF nanofiber, the charge decay time increased by more than 10 times. The former is more conducive to improving the power generation performance of the TENG, and the latter significantly improves the stability and repeatability of TENG-based sensors. .

The cell death-related genes machine learning model for precise therapy and clinical drug selection in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the prevailing subtype of hepatocellular malignancy. While previous investigations have evidenced a robust link with programmed cell death (PCD) and tumorigenesis, a comprehensive inquiry targeting the relationship between multiple PCDs and HCC remains scant. Our aim was to develop a predictive model for different PCD patterns in order to investigate their impact on survival rates, prognosis and drug response rates in HCC patients. We performed functional annotation and pathway analysis on identified PCD-related genes (PCDRGs) using multiple bioinformatics tools. The prognostic value of these PCDRGs was verified through a dataset obtained from GEO. Consensus clustering analysis was utilized to elucidate the correlation between diverse PCD clusters and pertinent clinical characteristics. To comprehensively uncover the distinct PCD regulatory patterns, our analysis integrated gene expression profiling, immune cell infiltration and enrichment analysis. To predict survival differences in HCC patients, we established a PCD model. To enhance the clinical applicability for the model, we developed a highly accurate nomogram. To address the treatment of HCC, we identified several promising chemotherapeutic agents and novel targeted drugs. These drugs may be effective in treating HCC and could improve patient outcomes. To develop a cell death feature for HCC patients, we conducted an analysis of 12 different PCD mechanisms using eligible data obtained from public databases. Through this analysis, we were able to identify 1254 PCDRGs likely to contribute to cell death on HCC. Further analysis of 1254 PCDRGs identified 37 genes with prognostic value in HCC patients. These genes were then categorized into two PCD clusters A and B. The categorization was based on the expression patterns of the genes in the different clusters. Patients in PCD cluster B had better survival probabilities. This suggests that PCD mechanisms, as represented by the genes in cluster B, may have a protective effect against HCC progression. Furthermore, the expression of PCDRGs was significantly higher in PCD cluster A, indicating that this cluster may be more closely associated with PCD mechanisms. Furthermore, our observations indicate that patients exhibiting elevated tumour mutation burden (TMB) are at an augmented risk of mortality, in comparison to those displaying low TMB and low-risk statuses, who are more likely to experience prolonged survival. In addition, we have investigated the potential distinctions in the susceptibility of diverse risk cohorts towards emerging targeted therapies, designed for the treatment of HCC. Moreover, our investigation has shown that AZD2014, SB505124, LJI308 and OSI-207 show a greater efficacy in patients in the low-risk category. Conversely, for the high-risk group patients, PD173074, ZM447439 and CZC24832 exhibit a stronger response. Our findings suggest that the identification of risk groups and personalized treatment selection could lead to better clinical outcomes for patients with HCC. Furthermore, significant heterogeneity in clinical response to ICI therapy was observed among HCC patients with varying PCD expression patterns. This novel discovery underscores the prospective usefulness of these expression patterns as prognostic indicators for HCC patients and may aid in tailoring targeted treatment for those of distinct risk strata. Our investigation introduces a novel prognostic model for HCC that integrates diverse PCD expression patterns. This innovative model provides a novel approach for forecasting prognosis and assessing drug sensitivity in HCC patients, driving a more personalized and efficacious treatment paradigm, elevating clinical outcomes. Nonetheless, additional research endeavours are required to confirm the model's precision and assess its potential to inform clinical decision-making for HCC patients.

Decoding the roles of heat shock proteins in liver cancer.

Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies, characterized by insidious onset and high propensity for metastasis and recurrence. Apart from surgical resection, there are no effective curative methods for HCC in recent years, due to resistance to radiotherapy and chemotherapy. Heat shock proteins (HSP) play a crucial role in maintaining cellular homeostasis and normal organism development as molecular chaperones for intracellular proteins. Both basic research and clinical data have shown that HSPs are crucial participants in the HCC microenvironment, as well as the occurrence, development, metastasis, and resistance to radiotherapy and chemotherapy in various malignancies, particularly liver cancer. This review aims to discuss the molecular mechanisms and potential clinical value of HSPs in HCC, which may provide new insights for HSP-based therapeutic interventions for HCC.

The impact of liver abscess formation on prognosis of patients with malignant liver tumors after transarterial chemoembolization.

Purpose: Liver abscess is a rare and serious complication after transarterial chemoembolization (TACE) for liver cancer; however, its impact on the prognosis is unclear. This retrospective study examined the outcomes of patients with liver abscess formation following TACE for malignant liver tumors to elucidate the impact of liver abscess formation on the prognosis of these patients. Methods: From January 2017 to January 2022, 1,387 patients with malignant tumors underwent 3,341 sessions of TACE at our hospital. Clinical characteristics of patients at baseline and follow-up were examined, including treatment and outcome of liver abscess, tumor response to the TACE leading to liver abscess, and overall survival time. Results: Of 1,387 patients, 15 (1.1%) patients with liver abscess complications after TACE resulted in a total of 16 (0.5%) cases of liver abscess after 3,341 TACE sessions (including one patient with two events). After antibiotic or percutaneous catheter drainage (PCD) treatment, all the infections associated with liver abscesses were controlled. In the PCD group, eight patients died before drainage tube removal, one retained the drainage tube until the end of follow-up, and five underwent drainage tube removal; the mean drainage tube removal time was 149.17 ± 134.19 days. The efficacy of TACE leading to liver abscess was evaluated as partial response (18.75%), stable disease (37.5%), and progressive disease (43.75%). Eleven patients died during the follow-up period owing to causes unrelated to infections caused by liver abscesses. The survival rates at 3 months, 6 months, 1 year, and 5 years were 86.7%, 50.9%, 25.5%, and 17%, respectively. Conclusion: Patients with liver abscess formation following TACE for malignant liver tumors experienced prolonged drainage tube removal time after PCD; while this condition did not directly cause death, it indirectly contributed to a poor prognosis in these patients.

LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis: A protective mechanism in the pathogenesis of atherosclerosis.

Atherosclerosis (AS), a metabolic disorder, is usually caused by chronic inflammation. LETM1 Domain-Containing Protein 1 (LETMD1) is a mitochondrial outer membrane protein required for mitochondrial structure. This study aims to evaluate the functional role of LETMD1 in endothelial pathogenesis of AS. Oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) and high-fat diet apolipoprotein E-deficient (ApoE-/-) mice were used to establish in vitro and in vivo models, respectively. Recombinant adenovirus vectors were constructed to investigate the role of LETMD1 in AS. mRNA sequencing was used to explore the effect of LETMD1 overexpression on gene expression in ox-LDL-induced HUVECs. A dual-luciferase reporting assay and chromatin immunoprecipitation (ChIP)-PCR were further conducted to verify the relationship between KLF4 and LETMD1. Results showed that LETMD1 was highly expressed in the aortas of atherosclerotic animals. LETMD1 overexpression reduced the expression of inflammatory factors, pyroptosis, ROS production, and NF-κB activation in ox-LDL-induced HUVECs, whereas LETMD1 knockdown had the opposite impact. LETMD1 overexpression was involved in regulating gene expression in ox-LDL-induced HUVECs. Overexpression of LETMD1 in mice reduced serum lipid levels as well as atherosclerotic lesions in the aortic roots. Furthermore, LETMD1 overexpression suppressed inflammatory reactions, cell pyroptosis, nuclear p65 protein level, cell apoptosis, and ROS generation in the aortas of AS mice. KLF4 (Krüppel-like factor 4) was found to be the transcriptional regulator of LETMD1. In conclusion, LETMD1, a target of KLF4, hinders endothelial inflammation and pyroptosis, which is a mechanism inhibiting the development of atherosclerosis.

KPNA2 Silencing, Regulated by E3 Ubiquitin Ligase FBXW7, Alleviates Endothelial Dysfunction and Inflammation Through Inhibiting the Nuclear Translocation of p65 and IRF3: A Possible Therapeutic Approach for Atherosclerosis.

Atherosclerosis (AS), characterized by a maladaptive inflammatory response, is one of the most common causes of death among the elderly. Karyopherin subunit alpha 2 (KPNA2), a member of the nuclear transport protein family, has been reported to play a pro-inflammatory role in various pathological processes by regulating the nuclear translocation of pro-inflammatory transcription factors. However, the function of KPNA2 in AS remains unknown. ApoE-/- mice were fed high-fat diets for 12 weeks to establish an AS mice model. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish an AS cell model. We found that KPNA2 was upregulated in the aortic roots of atherosclerotic mice and LPS-stimulated cells. KPNA2 knockdown inhibited LPS-induced secretion of pro-inflammatory factors and monocyte-endothelial adhesion in HUVECs, whereas KPNA2 overexpression exerted the opposite effects. p65 and interferon regulatory factor 3 (IRF3), the transcription factors known to regulate the transcription of pro-inflammatory genes, interacted with KPNA2, and their nuclear translocations were blocked following KPNA2 silencing. Furthermore, we found that KPNA2 protein level was decreased by E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBXW7), which was downregulated in the atherosclerotic mice. FBXW7 overexpression induced ubiquitination with subsequent proteasomal degradation of KPNA2. Meanwhile, the effects of KPNA2 deficiency on atherosclerotic lesions were further confirmed by in vivo experiments. Taken together, our study indicates that KPNA2 downregulation, regulated by FBXW7, may alleviate endothelial dysfunction and related inflammation in the progression of AS by suppressing the nuclear translocation of p65 and IRF3.

Systematic Review and Meta-Analysis of Drug-Coated Balloon Angioplasty for In-Stent Restenosis in Femoropopliteal Artery Disease.

PURPOSE: The present meta-analysis evaluated the role of drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR) in femoropopliteal artery disease. MATERIALS AND METHODS: Cochrane Library, Embase, and PubMed were searched without language restrictions from inception to May 10, 2020. The endpoints included target lesion revascularization (TLR), recurrent ISR, clinical improvement, ankle-brachial index (ABI), and death. There were 5 randomized controlled trials with 425 patients (218 with DCB angioplasty and 207 with plain old balloon angioplasty [POBA]) were included in the meta-analysis. RESULTS: Compared with POBA, DCB angioplasty was associated with lower risk of TLR (odds ratio [OR], 0.21; 95% confidence interval [CI]: 0.09-0.49, P < .001 at 6 months and OR, 0.15; 95% CI, 0.08-0.30; P < .001 at 12 months) and recurrent ISR (OR, 0.22; 95% CI, 0.13-0.38; P < .001 at 6 months and OR, 0.31; 95% CI, 0.16-0.61; P < .001 at 12 months), and superior clinical improvement (OR, 1.98; 95% CI, 1.07-3.65; P = .03 at 6 months and OR, 2.84; 95% CI: 1.50-5.35; P = .001 at 12 months). There were no significant differences between groups in ABI and death. Subgroup analysis for patients with DCB angioplasty showed similar rates of TLR, recurrent ISR, clinical improvement, and death between the short lesion (<15 cm) and long lesion group (≥15 cm) (P > .05). CONCLUSIONS: The current meta-analysis suggests that DCB angioplasty is an improvement over POBA for femoropopliteal ISR. Future studies about the effect of lesion length on DCB performance are still needed.

Feasibility of low-dose contrast media in run-off CT angiography on dual-layer spectral detector CT.

BACKGROUND: The aim of the present study was to assess the feasibility of applying low-dose contrast media (CM), and to explore the optimal virtual monoenergetic images (VMIs) in run-off computed tomography (CT) angiography (CTA) on dual-layer spectral detector CT (SDCT). METHODS: Forty patients were randomly assigned into a control group using routine volume CM (group A) and an experimental group using half-volume CM (group B). In groups A and B, 120 kVp polychromatic conventional images were generated via hybrid iterative reconstruction algorithm defined as A1 and B1, respectively. Additionally, in group B, VMIs (range, 40-120 keV) were reconstructed via a spectral reconstruction algorithm defined as B2-B10. Vascular attenuation, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and radiation dose were evaluated. Subjective evaluation was performed using a 5-point scale. RESULTS: The patient demographics and radiation dose demonstrated no significant difference between groups A and B [dose length product (DLP): 1,823.45±512.68 vs. 2,014.40±453.25 mGy·cm, P=0.229; volume CT dose index: 14.92±3.40 vs. 16.26±2.85 mGy, P=0.208; the effective dose (ED): 10.82±3.02 vs. 11.88±2.67 mSv, P=0.229]. The mean vascular attenuation was higher in group B2 (40 keV) and was lower in group B3 (50 keV) in comparison with that in group A1 (487.07±154.21 vs. 414.35±71.66 HU, 329.90±100.25 vs. 414.35±71.66 HU, P>0.05). Compared with group A1, the mean noise was similar in group B2 (40 keV) and was lower in group B1 and groups B3-B10 (50-120 keV) (14.81±5.67 vs. 17.29±4.70 HU, P>0.05; 6.75±1.23-11.26±3.24 vs. 17.29±4.70 HU, P<0.05). The mean SNR and CNR in group B2 (40 keV), as well as the mean SNR in group B3 (50 keV), were significantly higher than those of group A1 (38.21±7.52 vs. 28.25±7.20, 32.70±7.79 vs. 24.54±6.60, 32.85±7.10 vs. 28.25±7.20, P<0.05), and the mean CNR in group B3 (50 keV) was similar to that in group A1 (26.66±7.32 vs. 24.54±6.60, P>0.05). Scores of subjective image quality (IQ) in group B2 (40 keV) and B3 (50 keV) were similar to those in group A1 {5 [4.25, 5] vs. 5 [4, 5], 5 [5, 5] vs. 5 [4, 5], P>0.05}, and showed a declining trend in group B4 (60 keV) {4 [4, 5] vs. 5 [4, 5], P>0.05}. CONCLUSIONS: It is feasible to perform run-off CTA using low-dose CM with VMI on SDCT. The VMIs at 40-50 keV were the optimal choice and did not compromise IQ.

Assessment of Virtual Monoenergetic Images in Run-off Computed Tomography Angiography: A Comparison Study to Conventional Images From Spectral Detector Computed Tomography.

OBJECTIVE: The aims of this study were to evaluate image quality of virtual monoenergetic images (VMIs) compared with conventional images (CIs) from spectral detector CT (SDCT) and to explore the optimal energy level in run-off computed tomography angiography (CTA). METHODS: The data sets of 35 patients who received run-off CTA on the SDCT were collected in this retrospective study. Conventional images were generated via iterative reconstruction algorithm and VMI series from 40 to 120 keV were generated via spectral reconstruction algorithm. The objective indices including vascular attenuation, noise, signal-to-noise ratio, and contrast-to-noise ratio were compared. Two readers performed subjective evaluation using a 5-point scale. RESULTS: The attenuation showed higher values compared with CIs at 40 to 60 keV (P < 0.001). The noise was similar in 60- to 80-keV VMIs and significantly decreased in 90- to 120-keV VMIs (P < 0.001) in comparison with CIs. The signal-to-noise ratio and contrast-to-noise ratio were improved in 40- to 60-keV VMIs compared with CIs (P < 0.05). The score of subjective assessment was higher than that of CIs in 50- to 70-keV VMIs (P < 0.001). CONCLUSIONS: Virtual monoenergetic images can provide improved image quality compared with CIs from SDCT in run-off CTA, and VMIs at 60 keV may be the best choice in evaluating lower extremity arteries.

The lncRNA GAS5 Inhibits the Osteogenic Differentiation and Calcification of Human Vascular Smooth Muscle Cells.

Vascular calcification (VC), which is associated with high cardiovascular morbidity and mortality in patients with chronic kidney disease, is promoted by the osteoblastic differentiation of vascular smooth muscle cells (VSMCs). The present study explored the functional roles and molecular mechanisms of the long noncoding RNA growth arrest-specific transcript 5 (GAS5) in VC. Our results indicated that GAS5 was clearly downregulated in calcified human aortic vascular smooth muscle cells (HASMCs). Functionally, we found that overexpression of GAS5 significantly attenuated the osteogenic differentiation and calcification of HASMCs induced by high levels of phosphorus. Moreover, miR-26-5p was identified to potentially bind to GAS5, and phosphatase and tensin homolog (PTEN) was determined to be a direct target of miR-26b-5p in HASMCs. Mechanistically, enforced expression of miR-26-5p significantly attenuated PTEN protein expression in HASMCs. Rescue experiments demonstrated that cotransfection of HASMCs with miR-26-5p mimics reduced the inhibition of Lv-GAS5 on osteogenic differentiation and calcification. As a result, GAS5 was confirmed to be an miR-26b-5p sponge and to thereby increase the expression of PTEN in HASMCs. In ex vivo models, GAS5 was significantly downregulated and its expression inversely related to the expression of miR-26b-5 and positively associated with the expression of PTEN in calcified aortic rings induced by high levels of phosphorus. Together, these results suggest that the GAS5/miR-26-5p/PTEN axis could serve as a potential therapeutic target for VC in patients with chronic kidney disease.

Impact of pulmonary interstitial lesions on efficacy and prognosis of EGFR-TKI-treated advanced non-small cell lung cancers.

BACKGROUND: This study aimed to assess the impact of pre-existing pulmonary interstitial lesions (PIL) on the efficacy and prognosis of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitor (TKI). METHODS: Patients with advanced NSCLC harboring EGFR exon 19 deletion (E19 del) or exon 21 (E21) L858R were enrolled in this study. All patients underwent high resolution computed tomography (HRCT) chest scans prior to EGFR-TKI treatment. Pre-existing PIL was graded according to HRCT imaging (PIL 0, 1, 2, and 3). Cox proportional-hazards regression models were used to identify the prognostic factors for progression-free survival (PFS). RESULTS: A total of 134 eligible patients were enrolled. The overall objective response rate (ORR) and median PFS were 73.1% and 10.0 months (95% CI: 7.51-12.49), respectively. There were 62 (46.3%), 25 (18.7%), 28 (20.9%), and 19 (14.1%) cases of PIL grade 0, 1, 2, and 3, respectively, with median PFS and ORR of 12.9 months and 80.6%, 11.0 months and 72.0%, 10.0 months and 71.4%, and 7.0 months and 52.6%, respectively. Multivariate analysis showed that squamous cell carcinoma (vs. adenocarcinoma, HR =4.33), E21 L858R (vs. E19 del, HR =1.57), and PIL grade 3 (vs. grade 0-2, HR =1.60-2.48) were poor prognostic factors for PFS (P<0.05 for all). CONCLUSIONS: Pre-existing PIL grade is an independent prognostic factor for predicting resistance to EGFR-TKIs in patients with EGFR-mutant advanced NSCLC. Higher PIL grade suggests higher risk of early progression.

Platelet to lymphocyte ratio predicting 6-month primary patency of drug-coated balloon for femoropopliteal disease.

BACKGROUND: Inflammatory reaction is an essential factor in the occurrence, development and prognosis of femoropopliteal disease (FPD). The ratio of platelets to lymphocytes (PLR) is a new indicator reflecting platelet aggregation and burden of systemic inflammation. Our study is to explore the association between preoperative platelet-to-lymphocyte ratio (pre-PLR) and 6-month primary patency (PP) after drug-coated balloon (DCB) in FPD. METHODS: There were 70 patients who underwent DCB for FPD contained in the study. According to 6-month PP, patients were divided into group A (PP ≥6 months, n = 54) and group B (PP < 6 months, n = 16). Logistic regression analysis was used to identify potential predictors for 6-month PP after DCB in FPD. A receiver operating characteristic (ROC) curve analysis was used to identify the cut-off value of pre-PLR to predict 6-month PP. RESULTS: Logistic regression analysis showed that pre-PLR (OR: 1.008, 95% CI: 1.001-1.016, P = 0.031) and lesion length > 10 cm (OR: 4.305, 95% CI: 1.061-17.465, P = 0.041) were independently predictive for 6-month PP. The cutoff value of pre-PLR obtained from the ROC analysis was 127.35 to determine 6-month PP with the area of 0.839. Subgroup analysis was conducted based on the cutoff value of pre-PLR. The 6-month PP in the group of pre-PLR < 127.35 was higher than that of pre-PLR ≥ 127.35 group (p < 0.001). CONCLUSIONS: The present study indicated that an elevated pre-PLR was an effective additional indicator for predicting early PP in FPD after DCB.

Lower Limb Arterial Calcification and Acute Thrombosis Risk in Patients with Peripheral Artery Disease.

BACKGROUND: Calcification is closely related to in situ thrombosis secondary to plaque rupture in the coronary artery. However, the association between calcification in lower extremity arteries and acute thrombosis has not been assessed. We thus sought to determine whether lower limb arterial calcification (LLAC) was correlated with acute thrombosis in patients with symptomatic peripheral artery disease (PAD). METHODS: We retrospectively reviewed consecutive patients presenting with symptomatic PAD between April 2017 and March 2018 who underwent lower extremity arterial evaluation by computed tomography (CT) angiography. Patient characteristics and cardiovascular risk factors were recorded, and LLAC scores were determined by noncontrast CT scans. Univariate and multivariate logistic regression was used to identify factors associated with acute thrombosis. RESULTS: The record search identified 201 patients with symptomatic PAD, including 24 with acute thrombosis and 177 without. Patients in the acute thrombosis group were significantly younger (P = 0.04) and had less diabetes mellitus (P = 0.04). Patients with acute thrombosis had more advanced ischemia at presentation (P < 0.01) and higher amputation rate within 30 days (P < 0.01). Univariate regression showed a significant association among acute thrombosis and age, diabetes mellitus, and LLAC score; in multivariable analysis, only the LLAC score (odds ratio 0.60, 95% confidence interval 0.37-0.98) maintained an association with acute thrombosis after adjusting for relevant risk factors. CONCLUSIONS: The LLAC score is independently and inversely associated with acute thrombosis in patients with PAD.

Directional Atherectomy with Antirestenotic Therapy for Femoropopliteal Artery Disease: A Systematic Review and Meta-Analysis.

Systematic literature searches using Embase, PubMed, and Cochrane Library for directional atherectomy with antirestenotic therapy (DAART) in femoropopliteal artery disease (FPAD) from January 2003 to February 2018 were conducted to evaluate clinical safety and effectiveness. A meta-analysis was conducted using Stata software for the event rate of technical success, bailout stent placement, primary patency, and target lesion revascularization (TLR) at 12 months. Five studies with 189 patients who received DAART were included in the meta-analysis. Pooled rates of technical success and bailout stent placement were 90.4% (95% confidence interval [CI] 86.3%-94.6%) and 4.8% (95% CI 0.7%-8.9%), respectively. Primary patency and TLR at 12 months were 85.3% (95% CI 79.6%-91.1%) and 5.5% (95% CI 1.9%-9.1%), respectively. Meta-analysis of 3 comparative studies demonstrated that DAART was not superior in performance in clinical endpoints, including technical success, bailout stent placement, primary patency, and TLR at 12 months (relative risk [RR] 1.111, 95% CI 0.896-1.377, P = .337; RR 0.400, 95% CI 0.120-1.332, P = .135; RR 1.136, 95% CI 0.841-1.535, P = .405; and RR 0.722, 95% CI 0.291-1.789, P = .482). The data did not suggest that DAART was an improvement over paclitaxel-coated balloon angioplasty for FPAD. The theoretical advantages of DAART still require further confirmation.

Reticulocalbin 2 enhances osteogenic differentiation of human vascular smooth muscle cells in diabetic conditions.

AIM: Diabetes accelerates pro-atherogenic and pro-osteogenic phenotypes of vascular smooth muscle cells (VSMCs), an important process for vascular calcification. Reticulocalbin 2 (RCN2) is a candidate gene for atherosclerosis and involved in vascular remodeling in hypertension. However, the role of RCN2 in VSMCs calcification under diabetic conditions is unclear. MATERIALS AND METHODS: Expression of RCN2 and Runt-related transcription factor 2 (Runx2) in femoropopliteal arterial plaques was compared between type 2 diabetes mellitus (DM) and non-DM patients using immunohistochemical staining (IHCS). Human aortic VSMCs (HAVSMCs) were analyzed under RCN2 gene knockdown and overexpression conditions. Alizarin red staining and intracellular calcium deposition quantification were used to observe calcification induced in vitro under normal glucose or high glucose combined with ß-glycerol phosphoric acid conditions. The cells were investigated for gene modulation of osteogenic differentiation markers using Western blotting. KEY FINDINGS: The expression of RCN2 and Runx2 in femoropopliteal artery plaques was significantly higher in DM than in non-DM patients. In addition, a significant positive correlation was observed between RCN2 and Runx2 levels. RCN2 was highly expressed when HAVSMCs were treated with high glucose and the expression levels correlated with the calcification characteristics. RCN2 upregulated osteogenic transformation markers Runx2 and Osterix in HAVSMCs and downregulated contractile phenotype markers α-SMA and SM22α. SIGNIFICANCE: The results from this study indicate RCN2 is a major factor in mediating the calcification process of HAVSMCs in diabetic conditions. Thus, RCN2 may serve as a future therapeutic target for vascular calcification in diabetes.

A pooled analysis of transarterial radioembolization with yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma.

Purpose: The aim of this pooled analysis was to evaluate the clinical efficacy and safety of transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma (ICC). Methods: We searched the Cochrane Library, Embase, PubMed, SCI with the English language from inception to October 2018. A pooled analysis was conducted using Stata software. Results: There were 16 eligible studies included in this pooled analysis. The pooled median overall survival (OS) from 12 studies was 14.3 (95% CI: 11.9-17.1) months. Based on Response Evaluation Criteria in Solid Tumors (RECIST), no complete response was reported, and the median of partial response, stable disease and progressive disease were 11.5% (range: 4.8-35.3%), 61.5% (range: 42.9-81.3%) and 22.7% (range: 12.5-52.4%) respectively. The pooled disease control rate (DCR) from nine studies was 77.2% (95% CI: 70.2-84.2%). According to the type of microspheres, subgroup analysis was performed, the median OS in the glass microspheres group was 14.0 (95% CI: 9.1-21.4) months, and 14.3 (95% CI: 11.5-17.8) months in the resin microspheres group. The DCR was 77.3% (95% CI: 63.5-91.1%) and 77.4% (95% CI: 66.8-87.9%) in the glass and resin microspheres groups respectively. Most of the side effects reported in the included studies were mild and did not require intervention. Conclusion: TARE with 90Y microspheres is safe and effective for patients with unresectable ICC with acceptable side effects. And it seems that the type of microsphere has no influence on therapeutic efficacy.

Relationship Between Postoperative Neutrophil-Lymphocyte Ratio and 6-Month Primary Patency of Percutaneous Transluminal Angioplasty in Femoropopliteal disease With Drug-Coated and Uncoated Balloons.

We investigated the relationship of postoperative neutrophil-lymphocyte ratio (NLR) with 6-month primary patency of percutaneous transluminal angioplasty (PTA) in femoropopliteal disease using drug-coated balloon (DCB) or uncoated balloon (UCB). This retrospective study included 106 patients who received DCB (n = 44) or UCB (n = 62). The postoperative NLR was lower in the DCB group than that in the UCB group (2.60 vs 3.23; P = .004), and 6-month primary patency rate was significantly higher in DCB group than that in the UCB group (77.3% vs 53.2%; P = .011). Multivariate logistic analysis showed that the postoperative NLR was an independent predictor of 6-month primary patency after PTA in patients with femoropopliteal disease (odds ratio: 1.589, 95% confidence interval: 1.078-2.343; P = .019). The cutoff value of postoperative NLR was 3.05 for prediction of 6-month primary patency, with a sensitivity of 64.1% and specificity of 65.7%. The 6-month primary patency rate in the NLR ≤3.05 group was higher than that in the NLR >3.05 group (75.9% vs 47.9%; P = .003). In conclusion, DCB may improve early primary patency by inhibiting inflammation. A higher postoperative NLR was associated with early restenosis.

Combined Effects of Yttrium-90 Transarterial Radioembolization around Immunotherapy for Hepatic Metastases from Uveal Melanoma: A Preliminary Retrospective Case Series.

PURPOSE: To evaluate the safety and efficacy of yttrium-90 (90Y) transarterial radioembolization (TARE) around immunotherapy in patients with unresectable hepatic metastases from uveal melanoma (UM). MATERIALS AND METHODS: From March 2013 to December 2017, 11 patients with unresectable hepatic metastases from UM were treated with TARE around immunotherapy. Two patients received TARE as a first-line treatment followed by immunotherapy. Nine patients received immunotherapy before TARE, and 6 of these patients received additional immunotherapy after TARE. Retrospective review of the clinical data was performed to assess hepatic progression-free survival (hPFS), overall survival (OS), treatment response, and toxicities. The median follow-up period from TARE was 10.5 months (range 1-35.5 months). RESULTS: The median OS from diagnosis of hepatic metastases was 35.5 months (95% confidence interval [CI] 10.0-55.0 months). The median hPFS and OS from the start of TARE were 15.0 months (95% CI 5.9-24.1 months) and 17.0 months (95% CI 1.8-32.2 months), respectively. Complete response was observed in 1 patient (9.1%), partial response in 2 (18.2%), stable disease in 4 (36.4%), and progressive disease in 4 (36.4%). Ten patients had grade 1 or 2 clinical toxicities, and 1 had grade 3 with a peptic ulcer. Six patients had grade 1 or 2 biochemical toxicities and 1 had grade 3, which was related to tumor progression. CONCLUSIONS: The present results suggest that TARE around immunotherapy is safe and effective. The combined treatment may improve hPFS and OS in patients with hepatic metastases from UM.

Metabolic Characterization of Peripheral Host Responses to Drainage-Resistant Klebsiella pneumoniae Liver Abscesses by Serum 1H-NMR Spectroscopy.

Purpose: To explore the metabolic characterization of host responses to drainage-resistant Klebsiella pneumoniae liver abscesses (DRKPLAs) with serum 1H-nuclear magnetic resonance (NMR) spectroscopy. Materials and Methods: The hospital records of all patients with a diagnosis of a liver abscess between June 2015 and December 2016 were retrieved from an electronic hospital database. Eighty-six patients with Klebsiella pneumoniae (K. pneumoniae) liver abscesses who underwent percutaneous drainage were identified. Twenty patients with confirmed DRKPLAs were studied. Moreover, we identified 20 consecutive patients with drainage-sensitive Klebsiella pneumoniae liver abscesses (DSKPLAs) as controls. Serum samples from the two groups were analyzed with 1H NMR spectroscopy. Partial least squares discriminant analysis (PLS-DA) was used to perform 1H NMR metabolic profiling. Metabolites were identified using the Human Metabolome Database, and pathway analysis was performed with MetaboAnalyst 3.0. Results: The PLS-DA test was able to discriminate between the two groups. Five key metabolites that contributed to their discrimination were identified. Glucose, lactate, and 3-hydroxybutyrate were found to be upregulated in DRKPLAs, whereas glutamine and alanine were downregulated compared with the DSKPLAs. Pathway analysis indicated that amino acid metabolisms were significantly different between the DRKPLAs and the DSKPLAs. The D-glutamine and D-glutamate metabolisms exhibited the greatest influences. Conclusions: The five key metabolites identified in our study may be potential targets for guiding novel therapeutics of DRKPLAs and are worthy of additional investigation.