Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.

BACKGROUND: Extrachromosomal circular DNA (eccDNA) has emerged as a promising biomarker for disease diagnosis and prognosis prediction. However, its role in type 2 diabetes remains unexplored. OBJECTIVE: To investigate the characteristics and dynamics of circulating eccDNAs in newly diagnosed type 2 diabetes mellitus (T2DM) patients undergoing short-term intensive insulin therapy (SIIT), a highly effective treatment for inducing long-term glycemic remission. METHODS: We conducted Circle-Seq analysis on plasma samples from 35 T2DM patients at three time points: pre-SIIT, post-SIIT, and 1-year post-SIIT. Our analysis encompassed the characterization of eccDNA features, including GC content, eccDNA length distribution, genomic distribution, and the genes in eccDNAs. RESULTS: Following SIIT, we observed an increase in plasma eccDNA load, suggesting metabolic alterations during therapy. Notably, a correlation was identified between eccDNA profiles and glycemia in T2DM, both quantitatively and genetically. Our analysis also revealed the frequent presence of metabolism-related genes within T2DM plasma eccDNAs, some of which spanned gene exons and/or fractions. CONCLUSION: This study represents the first report of cell-free eccDNA in T2DM and underscores a compelling association between cell-free eccDNA and profound glycemic changes. These findings highlight the potential of eccDNAs as crucial players in the context of T2DM and glycemic control.

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is probably the only tumor in which a unique epigenetic alteration, namely methylation of the MGMT gene, possesses direct clinical relevance. Now with the emergence of aberrant N6 methyladenosine (m6A) modifications (the most common epigenetic modification of mRNA, closely linked to the autophagy process) in cancer, the epi-transcriptomic landscape of GBM pathobiology has been expanded. Considering this, herein, we systematically analyzed m6A regulators, assessed their correlation with autophagy-related genes (ATG), and established a long non-coding RNAs (lncRNA)-dependent prognostic signature (m6A-autophagy-lncRNAs) for GBM. Our analysis identified a novel signature of five long non-coding RNAs (lncRNAs: ITGA6-AS1, AC124248.1, NFYC-AS1, AC025171.1, and AC005229.3) associated with survival of GBM patients, and four among them clearly showed cancer-associated potential. We further validated and confirmed the altered expression of two lncRNAs (AC124248.1, AC005229.3) in GBM associated clinical samples using RT-PCR. Concerning the prognostic ability, the obtained signature determined high-/low-risk groups in GBM patients and showed sensitivity to anticancer drugs. Collectively, the m6A-autophagy-lncRNAs signature presented in the study is clinically relevant and is the first attempt to systematically predict the potential interaction between the three key determinants (m6A, autophagy, lncRNA) in cancer, particularly in GBM.

Computational analysis of heat shock proteins and ferroptosis-associated lncRNAs to predict prognosis in acute myeloid leukemia patients.

Owing to their functional diversity in many cancers, long noncoding RNAs (lncRNAs) are receiving special attention. LncRNAs not only function as oncogenes or tumor suppressors by participating in various signaling pathways but also serve as predictive markers for various types of cancer, including acute myeloid leukemia (AML). Considering this, we investigated lncRNAs that may act as a mediator between two processes, i.e., heat shock proteins and ferroptosis, which appear to be closely related in tumorigenesis. Using a comprehensive bioinformatics approach, we identified four lncRNAs (AL138716.1, AC000120.1, AC004947.1, and LINC01547) with prognostic value in AML patients. Of interest, two of them (AC000120.1 and LINC01547) have already been reported to be AML-related, and AC004947.1 is considered to have oncogenic potential. In particular, the signature obtained showed a lower survival probability with high-risk patients, and vice versa. To our knowledge, this is the first predictive model of lncRNA that may correlate with the processes of heat shock proteins and ferroptosis in AML. Nevertheless, validation using patient samples is warranted.

Cytokine-Induced Killer Cells in Combination with Heat Shock Protein 90 Inhibitors Functioning via the Fas/FasL Axis Provides Rationale for a Potential Clinical Benefit in Burkitt's lymphoma.

Constant efforts are being made to develop methods for improving cancer immunotherapy, including cytokine-induced killer (CIK) cell therapy. Numerous heat shock protein (HSP) 90 inhibitors have been assessed for antitumor efficacy in preclinical and clinical trials, highlighting their individual prospects for targeted cancer therapy. Therefore, we tested the compatibility of CIK cells with HSP90 inhibitors using Burkitt's lymphoma (BL) cells. Our analysis revealed that CIK cytotoxicity in BL cells was augmented in combination with independent HSP90 inhibitors 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) and ganetespib. Interestingly, CIK cell cytotoxicity did not diminish after blocking with NKG2D (natural killer group 2, member D), which is a prerequisite for their activation. Subsequent analyses revealed that the increased expression of Fas on the surface of BL cells, which induces caspase 3/7-dependent apoptosis, may account for this effect. Thus, we provide evidence that CIK cells, either alone or in combination with HSP90 inhibitors, target BL cells via the Fas-FasL axis rather than the NKG2D pathway. In the context of clinical relevance, we also found that high expression of HSP90 family genes (HSP90AA1, HSP90AB1, and HSP90B1) was significantly associated with the reduced overall survival of BL patients. In addition to HSP90, genes belonging to the Hsp40, Hsp70, and Hsp110 families have also been found to be clinically significant for BL survival. Taken together, the combinatorial therapy of CIK cells with HSP90 inhibitors has the potential to provide clinical benefits to patients with BL.

Ticagrelor plus aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended as the secondary prevention of minor ischemic stroke or transient ischaemic attack (TIA). However, genetic polymorphisms of CYP2C19 had been identified as the major cause of poor responsiveness to clopidogrel. Ticagrelor, unlike clopidogrel, did not depend on metabolic activation, but it remained unclear whether ticagrelor was superior to clopidogrel in ischemic stroke. We performed a network meta-analysis to compare the efficacy and safety of ticagrelor, clopidogrel, and aspirin in the minor ischemic stroke and TIA populations. METHODS: Databases of Cochrane Library, ClinicalTrials.gov, and PubMed were searched up to June 19, 2023. Randomized controlled trials (RCTs) assessing antiplatelet drugs for minor stroke or TIA were included. Statistical processing was conducted by using multivariate meta-analysis routines of STATA. RESULTS: Seven RCTs were included involving 41,745 participants. There was no significant difference between the two DAPTs in preventing stroke recurrence (OR, 1.16; 95% CI, 0.93-1.44), ischemic stroke recurrence (OR, 1.16; 95% CI, 0.93-1.45), and major hemorrhage (OR, 1.22; 95% CI, 0.62,2.39). Compared with aspirin alone, the two DAPT regimen reduced the risk of stroke recurrence (clopidogrel: OR, 0.69; 95% CI, 0.60-0.80, ticagrelor: OR, 0.66; 95% CI, 0.49-0.87) and ischemic stroke recurrence, but increased the incidence of major hemorrhage (clopidogrel: OR, 2.05; 95% CI, 1.22- 3.77; ticagrelor: OR, 2.55; 95% CI, 1.25-4.99). Despite being associated with a higher risk of any bleeding, ticagrelor did not impact the composite of vascular events or mortality. While ticagrelor and aspirin reduced the risk of ischemic stroke recurrence (OR, 0.77; 95% CI, 0.63- 0.92) without increasing the risk of major bleeding (OR 0.94; 95% CI 0.45-1.95) in the Asian population mainly Chinese. CONCLUSIONS: DAPT was superior to aspirin in stroke prevention, but little difference existed between the two DAPT regimens. Asian population mainly Chinese may benefit from DAPT with aspirin and ticagrelor. But further head-to-head RCTs are needed to validate the study results.

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells.

Emerging evidence suggests that chemotherapeutic agents and targeted anticancer drugs have serious side effects on the healthy cells/tissues of the patient. To overcome this, the use of non-oncology drugs as potential cancer therapies has been gaining momentum. Herein, we investigated one non-oncology drug named meticrane (a thiazide diuretic used to treat essential hypertension), which has been reported to indescribably improve the therapeutic efficacy of anti-CTLA4 in mice with AB1 HA tumors. In our hypothesis-driven study, we tested anti-cancer potential meticrane in hematological malignance (leukemia and multiple myeloma) and liver cancer cell lines. Our analysis showed that: 1) Meticrane induced alteration in the cell viability and proliferation in leukemia cells (Jurkat and K562 cells) and liver cancer (SK-hep-1), however, no evidence of apoptosis was detectable. 2) Meticrane showed additive/synergistic effects with epigenetic inhibitors (DNMT1/5AC, HDACs/CUDC-101 and HDAC6/ACY1215). 3) A genome-wide transcriptional analysis showed that meticrane treatment induces changes in the expression of genes associated with non-cancer associated pathways. Of importance, differentially expressed genes showed favorable correlation with the survival-related genes in the cancer genome. 4) We also performed molecular docking analysis and found considerable binding affinity scores of meticrane against PD-L1, TIM-3, CD73, and HDACs. Additionally, we tested its suitability for immunotherapy against cancers, but meticrane showed no response to the cytotoxicity of cytokine-induced killer (CIK) cells. To our knowledge, our study is the first attempt to identify and experimentally confirm the anti-cancer potential of meticrane, being also the first to test the suitability of any non-oncology drug in CIK cell therapy. Beyond that, we have expressed some concerns confronted during testing meticrane that also apply to other non-oncology drugs when considered for future clinical or preclinical purposes. Taken together, meticrane is involved in some anticancer pathways that are passively targeting cancer cells and may be considered as compatible with epigenetic inhibitors.

METTL3/m6A/IFIT2 regulates proliferation, invasion and immunity in esophageal squamous cell carcinoma.

Epigenetic regulation plays a critical role in the development, progression, and treatment of tumors. The most common chemical modification of mRNA, called m6A, is essential for controlling mRNA stability, splicing, and translation. Methyltransferase-like 3 (METTL3) is an important m6A methyltransferase. The mechanism of action of METTL3 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this investigation, we sought to clarify the function and clinical importance of METTL3 in ESCC and investigate its underlying mechanisms. We discovered that METTL3 has a significant proliferative effect in ESCC cells by using lentiviral construction of stable cell lines overexpressing METTL3 (METTL3-OE) and knocking down METTL3 (sh-METTL3). To create a xenograft tumor model, we inoculated KYSE510 cells subcutaneously into BALB/c nude mice and discovered that sh-METTL3 inhibited the tumorigenicity of esophageal cancer KYSE510 cells in the nude mouse tumor model. MeRIP-seq and RNA-seq analysis revealed IFIT2 to be a METTL3 target gene. The findings revealed that METTL3 regulates IFIT2 and thus influences malignant biological behaviors such as proliferation, migration, and invasion of ESCC, as well as the immune microenvironment of tumors.

Hydrothermal Corrosion of SiC Coupons Suppressed by Magnetron Sputtered Cr Coatings.

SiC-based components are sometimes susceptible to aqueous dissolution in LWR coolant environments. To address this issue, ~10 µm thick Cr coatings was deposited on reaction-bonded silicon carbide (RBSC) plates by magnetron sputtering. Corrosion behavior of Cr-coated SiC and -uncoated SiC coupons was studied by immersing in autoclave (345°C and 16.5 MPa). The weight loss of the Cr coated SiC coupons (3.02% after the 93-days) in the autoclave tests was effectively reduced due to their Cr-coated surfaces, in contrast to the uncoated ones (20.4% after the 78-days). Moreover, microstructural and compositional evolutions were examined by using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy. It was revealed that a continuous and dense Cr2O3 layer formed on the surface after the hydrothermal corrosion, which can suppress the in-diffusion of corrosive medium.

Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs) Harboring Oncogenic Potential and Is Markedly Upregulated in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is at the forefront of the global cancer burden, and biomarkers for HCC are constantly being sought. Interestingly, RGS (Regulators of G protein signaling) proteins, which negatively regulate GPCR signaling, have been associated with various cancers, with some members of the RGS family being associated with liver cancer as well. Considering this, we investigated the role of RGS20 as a potential prognostic marker in 28 different cancer types with special emphasis on HCC. By using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data, our analysis revealed that (a) RGS20 was strongly upregulated in tumor tissue compared with adjacent normal tissue of HCC patients; (b) RGS20 was strongly associated with some important clinical parameters such as alpha-fetoprotein and tumor grade in the HCC patients; (c) besides HCC (p < 0.001), RGS20 was found to be an important factor for survival in four other cancers (clear renal cell carcinoma: p < 0.001, lung adenocarcinoma: p = 0.004, mesothelioma: p = 0.039, ovarian serous cystadenocarcinoma: p = 0.048); (d) RGS20 was found to be significantly associated with some tumor-related signaling pathways and long intergenic non-coding RNAs (lincRNAs: LINC00511, PVT1, MIR4435-2HG, BCYRN1, and MAPKAPK5-AS1) that exhibit oncogenic potential. Taken together, we showed that RGS20 correlates with a few HCC-associated lincRNAs harboring oncogenic potential and is markedly upregulated in HCC patients. Our analysis further supports the putative function of RGS proteins, particularly RGS20, in cancer.

FTO mediated ERBB2 demethylation promotes tumor progression in esophageal squamous cell carcinoma cells.

N6-methyladenosine (m6A) is the most prevalent and internal modification that occurs in the messenger RNAs of eukaryotes. However, knowledge of the impact of these modifications on gene expression regulation remains limited. By using the in vitro MeRIP-seq and RNA-seq assays, we discovered that the mRNA demethylase FTO was significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and cells. Knockdown of FTO drastically suppressed the proliferation, migration, and invasion of ESCC cells. Furthermore, by using transcriptome-wide m6A-seq and RNA-seq assays, we identified ERBB2 is the target of FTO, which acts in concert in ESCC tumorigenesis and metastasis. Moreover, loss and gain functional studies suggested that the m6A reader YTHDF1 stabilizes ERBB2 mRNA via decoding the m6A modification. All these results uncovered a new signaling cascade, including FTO, YTHDF1, and ERBB2, which finely regulates the ESCC progression.

The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment.

It is well known that tumor cells rely mainly on aerobic glycolysis for energy production even in the presence of oxygen, and glycolysis is a known modulator of tumorigenesis and tumor development. The tumor microenvironment (TME) is composed of tumor cells, various immune cells, cytokines, and extracellular matrix, among other factors, and is a complex niche supporting the survival and development of tumor cells and through which they interact and co-evolve with other tumor cells. In recent years, there has been a renewed interest in glycolysis and the TME. Many studies have found that glycolysis promotes tumor growth, metastasis, and chemoresistance, as well as inhibiting the apoptosis of tumor cells. In addition, lactic acid, a metabolite of glycolysis, can also accumulate in the TME, leading to reduced extracellular pH and immunosuppression, and affecting the TME. This review discusses the significance of glycolysis in tumor development, its association with the TME, and potential glycolysis-targeted therapies, to provide new ideas for the clinical treatment of tumors.

Fatty acid profile as an efficient bioindicator of PCB bioaccumulation in a freshwater lake food web: A stable isotope guided investigation.

In past studies, the health and ecological risks of PCBs are well established. The impact of low-dose PCBs on aquatic ecosystems for an extended period is a matter of concern in the current era. The application of fatty acids (FAs) as bioindicators of pollution in the freshwater food web is almost unavailable. This study investigated concentrations of 209 PCB congeners, stable isotope levels, and FAs composition in ten freshwater species of Dongtinghu Lake, China. Total PCB congeners (∑PCBs) concentrations were ranged from 4.17 to 38.35 ng/g lipid weight. A total of 84 PCB congeners were detected out of 209 target PCB congeners, particularly PCB101, 118, 138, 153, and 155 found in all samples. The concentrations of 24 PCB congeners increased with trophic levels, but PCB 155 concentrations were consistent throughout trophic levels. The toxic equivalents (TEQ) of dl-PCBs (mostly PCB 126 and 169) also increased with trophic levels Out of total 35 FAs, 21 FAs were significantly positively correlated with 43 PCB congeners. Among FAs, C16:0 was the most abundant and positively correlated with most PCB compounds. Positive correlations between FAs and PCBs indicated that FAs can be used as efficient bioindicators of PCBs pollution in the aquatic food web.

Immunoautophagy-Related Long Noncoding RNA (IAR-lncRNA) Signature Predicts Survival in Hepatocellular Carcinoma.

BACKGROUND: The dysregulation of autophagy and immunological processes has been linked to various pathophysiological conditions, including cancer. Most notably, their particular involvement in hepatocellular carcinoma (HCC) is becoming increasingly evident. This has led to the possibility of developing a prognostic signature based on immuno-autophagy-related (IAR) genes. Given that long non-coding RNAs (lncRNAs) also play a special role in HCC, a combined signature utilizing IAR genes and HCC-associated long noncoding RNAs (as IARlncRNA) may potentially help in the clinical scenario. METHOD: We used Pearson correlation analysis, Kaplan-Meier survival curves, univariate and multivariate Cox regression, and ROC curves to generate and validate a prognostic immuno-autophagy-related long non-coding RNA (IARlncRNA) signature. The Chi-squared test was utilized to investigate the correlation between the obtained signature and the clinical characteristics. CIBERSORT algorithms and the Wilcoxon rank sum test were applied to investigate the correlation between signature and infiltrating immune cells. GO and KEGG analyses were performed to derived signature-dependent pathways. RESULTS: Herein, we build an IAR-lncRNA signature (as first in the literature) and demonstrate its prognostic ability in hepatocellular carcinoma. Primarily, we identified three IARlncRNAs (MIR210HG, AC099850.3 and CYTOR) as unfavorable prognostic determinants. The obtained signature predicted the high-risk HCC group with shorter overall survival, and was further associated with clinical characteristics such as tumor grade (t = 10.918, p = 0.001). Additionally, several infiltrating immune cells showed varied fractions between the low-risk group and the high-risk HCC groups in association with the obtained signature. In addition, pathways analysis described by the signature clearly distinguishes both risk groups in HCC. CONCLUSIONS: The immuno-autophagy-related long non-coding RNA (IARlncRNA) signature we established exhibits a prognostic ability in hepatocellular carcinoma. To our knowledge, this is the first attempt in the literature to combine three determinants (immune, autophagy and LnRNAs), thus requiring molecular validation of this obtained signature in clinical samples.

LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells.

Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.

PID: An integrative and comprehensive platform of plant intron.

Intron is a non-coding sequence of a broken gene and participates in important biological processes, such as transcription regulation, alternative splicing, and nuclear export. With the development of plant genomes, a comprehensive platform for intron analysis in plants must be established. Plant Intron Database (PID), a publicly available searchable database, was developed to efficiently store, query, analyze, and integrate intron resources in plants. The information of intron, exon, and gene can be searched by key words in PID. Users cannot only view intron length distribution pie chart and 5' and 3' splice site sequence feature maps in a statistical interface but can also browse intron information in a graphical visualization interface through JBrowse. ViroBlast for sequence homology searches, Intron detection and sequence interception tools were also provided. PID contains annotated genes from 118 sequenced plants, 24,782,048 introns, 30,843,049 exons, and 414 visual maps. This tool will greatly accelerate research on the distribution, length characteristics, and functions of introns in plants. PID is accessible at http://biodb.sdau.edu.cn/PID/index.php.

Lattice Defects and Exfoliation Efficiency of 6H-SiC via H2+ Implantation at Elevated Temperature.

Silicon carbide (SiC) is an important material used in semiconductor industries and nuclear power plants. SiC wafer implanted with H ions can be cleaved inside the damaged layer after annealing, in order to facilitate the transfer of a thin SiC slice to a handling wafer. This process is known as "ion-cut" or "Smart-Cut". It is worth investigating the exfoliation efficiency and residual lattice defects in H-implanted SiC before and after annealing. In the present paper, lattice damage in the 6H-SiC implanted by H2+ to a fluence of 5 × 1016 H2+/cm2 at 450 and 900 °C was investigated by a combination of Raman spectroscopy and transmission electron microscopy. Different levels of damage caused by dynamic annealing were observed by Raman spectroscopy and transmission electron microscopy in the as-implanted sample. Atomic force microscopy and scanning white-light interferometry were used to observe the sample surface morphology. Surface blisters and exfoliations were observed in the sample implanted at 450 °C and then annealed at 1100 °C for 15 min, whereas surface blisters and exfoliation occurred in the sample implanted at 900 °C without further thermal treatment. This finding can be attributed to the increase in the internal pressure of platelets during high temperature implantation. The exfoliation efficiency, location, and roughness after exfoliation were investigated and possible reasons were discussed. This work provides a basis for further understanding and improving the high-efficiency "ion-cut" technology.

A risk predictor of restenosis after superficial femoral artery stent implantation: relevance of mean platelet volume.

BACKGROUND: To investigate the relationship between an increase in the pre- and post-operative mean platelet volume (MPV) and superficial femoral artery in-stent restenosis (ISR) rate. METHODS AND RESULTS: We recruited patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to March 2018. All patients gave venous blood three days before and following implantation. Doppler ultrasound, computed tomography angiography or digital subtraction angiography were used for regular follow-up examination. Logistic regression was used to identify predictors of ISR after superficial femoral artery stenting. We enrolled 173 patients, of which 34 (19.6%) were determined as having ISR for a mean of 8.9 ± 2.7 months (3-12 months). Neutrophil count, neutrophil ratio, lymphocyte ratio and platelet count pre-implantation, and platelet count and MPV after stent implantation, and the pre- and post-operative mean platelet volume difference (MPVD) and mean platelet volume difference ratio (MPVDR) were all statistically different when comparing the ISR and non-restenosis groups (p < 0.05). A positive correlation was found for post-operative MPV and presence of ISR (r = 0.58; P < 0.001). A MPVD not less than 1.5 fL was associated with an odds ratio of 9.17 (95% CI [3.76 to 22.35]; P < 0.001) for presence of ISR. A MPVDR of not less than 17.9% was associated with an odds ratio of 7.68 (95% CI [3.19 to 18.49]; P < 0.001) for occurrence of ISR. CONCLUSIONS: An increase in pre- and post-operative MPV was correlated with the occurrence of superficial femoral artery ISR.

The relationship between neutrophil-lymphocyte ratio and in-stent restenosis in superficial femoral artery.

The present study aimed to investigate the relationship between an increase in the pre- and post-operative neutrophil-lymphocyte ratio (NLR) and superficial femoral artery in-stent restenosis (ISR) rate. We recruited 199 patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to July 2018. Patients were divided into two groups according to the occurrence of ISR within 1 year (group 1, ISR and group 2, Non-ISR). The after NLR (NLRafter) and NLR change ratio (NLRratio) (P<0.001) were significantly higher in group 1. A NLRafter > 4.3 was associated with an odds ratio of 1.946 (95% CI [1.51-2.50]; P<0.001) for the presence of ISR. A NLRratio > 37.5% was associated with an odds ratio of 3.6 (95% CI [2.03-6.36]; P<0.001) for occurrence of ISR. A NLRafter level > 4.3 had 75% sensitivity and 76% specificity for the prediction of ISR, as identified by the ROC curve. A NLRratio level > 37.5% predicted ISR with 77% sensitivity and 60% specificity. Multivariate logistic regression analysis demonstrated that NLRratio was the strongest independent predictor of ISR (P<0.001). In conclusions, NLRratio could be used as a prognostic marker in superficial femoral artery stents.

Effect of low dose naloxone on the immune system function of a patient undergoing video-assisted thoracoscopic resection of lung cancer with sufentanil controlled analgesia - a randomized controlled trial.

BACKGROUND: Perioperative immune function plays an important role in the prognosis of patients. Several studies have indicated that low-dose opioid receptor blockers can improve immune function. METHODS: Sixty-nine patients undergoing video-assisted thoracoscopic resection of the lung cancer were randomly assigned to either the naloxone group (n = 35) or the non-naloxone group (n = 34) for postoperative analgesia during the first 48 h after the operation. Both groups received sufentanil and palonosetron via postoperative analgesia pump, while 0.05 µg·kg- 1·h- 1 naloxone was added in naloxone group. The primary outcomes were the level of opioid growth factor (OGF) and immune function assessed by natural killer cells and CD4+/CD8+ T-cell ratio. Second outcomes were assessed by the intensity of postoperative pain, postoperative rescue analgesia dose, postoperative nausea and vomiting (PONV). RESULTS: The level of OGF in the naloxone group increased significantly at 24 h (p<0.001) and 48 h after the operation (P < 0.01). The natural killer cells (P < 0.05) and CD4+/CD8+ T-cell ratio (P < 0.01) in the naloxone group increased significantly at 48 h after the operation. The rest VAS scores were better with naloxone at 12 and 24 h after operation(P < 0.05), and the coughing VAS scores were better with naloxone at 48 h after the operation(P < 0.05). The consumption of postoperative rescue analgesics in the naloxone group was lower (0.00(0.00-0.00) vs 25.00(0.00-62.50)), P < 0.05). Postoperative nausea scores at 24 h after operation decreased in naloxone group(0.00 (0.00-0.00) vs 1.00 (0.00-2.00), P < 0.01). CONCLUSION: Infusion of 0.05 µg·kg- 1·h- 1 naloxone for patients undergoing sufentanil-controlled analgesia for postoperative pain can significantly increase the level of OGF, natural killer cells, and CD4+/CD8+ T-cell ratio compared with non-naloxone group, and postoperative pain intensity, request for rescue analgesics, and opioid-related side effects can also be reduced. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on January 26, 2019 (ChiCTR1900021043).