Protective effect of isoliquiritigenin in amiodarone-induced damage of human umbilical vein endothelial cells.

OBJECTIVE: Amiodarone (AM) is a drug commonly used in patients with ventricular arrhythmias. It can damage vascular endothelial cells and easily cause phlebitis. At present, the prevention and treatment of phlebitis induced by the use of AM is not clear due to the lack of corresponding primary research. Isoliquiritigenin (ISL) has an anti-inflammatory effect, but until now, has not been explored much in the field of research in primary care nursing. The purpose of this study is to investigate the efficacy and mechanism of action of ISL in treating phlebitis induced by AM. METHODS: In our study, we used human umbilical vein endothelial cells (HUVECs) that were divided into three groups: the NC group (normal), the AM group (AM 30 µmol/L for 24 h), and the ISL pretreatment group (isoliquiritigenin 10 µmol/L after 1 h of pretreatment with amiodarone for 24 h). We used CCK-8 to detect cell proliferation, cell scratch assay to detect the migration capability of cells, flow cytometry to measure apoptosis, angiogenesis assay to check the total length and total branches of angiogenesis, and PCR and WB to detect the expression of PCNA, casepase-3, and VEGFA. WB was used to detect NF-κBp65 and p-NF-κBp65 expression. RESULTS: Compared with the AM group, the ISL pretreatment promoted cell proliferation and migration, inhibited cell apoptosis, increased the total length and total branches of angiogenesis, and downregulated p-NF-κBp65 expression. CONCLUSION: ISL shows promise in the prevention and treatment of clinical phlebitis and can be used as a potential therapeutic drug to prevent phlebitis.

Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia.

Transient receptor potential vanilloid 1 (TRPV1) ion channel is a classic analgesic target, but antagonists of TRPV1 failed in clinical trials due to their side effects like hyperthermia. Here we rationally engineer a peptide s-RhTx as a positive allosteric modulator (PAM) of TRPV1. Patch-clamp recordings demonstrate s-RhTx selectively potentiated TRPV1 activation. s-RhTx also slows down capsaicin-induced desensitization of TRPV1 in the presence of calcium to cause more calcium influx in TRPV1-expressing cells. In addition, our thermodynamic mutant cycle analysis shows that E652 in TRPV1 outer pore specifically interacts with R12 and K22 in s-RhTx. Furthermore, we demonstrate in vivo that s-RhTx exhibits long-lasting analgesic effects in noxious heat hyperalgesia and CFA-induced chronic inflammatory pain by promoting the reversible degeneration of intra-epidermal nerve fiber (IENF) expressing TRPV1 channels in mice, while their body temperature remains unaffected. Our results suggest s-RhTx is an analgesic agent as a PAM of TRPV1.

Intermediate risk pulmonary embolism concomitant with or without lung cancer: a wide spectrum of features.

OBJECTIVES: We aimed to investigate the differences in clinical features between pulmonary embolism (PE) patients concomitant with lung cancer and without lung cancer (LC) and gain further understanding of the impact of lung cancer on pulmonary embolism. METHODS: This retrospective study sampled 114 patients diagnosed with pulmonary embolism from January 2017 to April 2021 in the First Affiliated Hospital of Soochow University. The patients were categorized into the LC group (n = 22) or non-LC group (n = 92). Myocardial injury, coagulation and blood cell parameters, along with imaging findings, were analyzed for the two groups. The primary outcome measure was the 90-day mortality. RESULTS: Of the 114 patients with pulmonary embolism in the present study, the 90 intermediate-risk patients were enrolled for further investigations. Compared to the non-LC group, patients in the LC group had milder myocardial injury, more severe coagulation function disorder, a higher incidence of central PE and a smaller change in diameter of the main pulmonary artery. We found that the occurrence of pericardial effusion created the risk of lung cancer in patients with pulmonary embolism, but there was no increase in the 90-day mortality for non-LC group versus LC group. CONCLUSION: Intermediate risk PE patients concomitant with lung cancer seem to be more likely to present specific clinical features, accordingly, clinicians must pay great attention to PE patients concomitant with lung cancer and implement effective treatments to simultaneously manage the two conditions.

Empathetic nursing with mindful cognitive therapy for fatigue, depression, and negative emotions in leukemia patients undergoing long-term chemotherapy.

BACKGROUND: Leukemia is a broad term for blood cell cancer. Leukemia is divided into acute or chronic, depending on cell differentiation. Leukemia patients are prone to adverse reactions during chemotherapy, such as anxiety, depression, and even suicide, affecting prognosis. As a nursing model developed by three well-known cognitive psychologists, empathetic nursing with mindfulness cognitive therapy (ENMCT) can effectively reduce anxiety and depression and improve the quality of life in patients with chronic disease. AIM: To explore the effect of ENMCT on cancer-induced fatigue, hope level, and negative emotions in patients with long-term leukemia chemotherapy. METHODS: A total of 103 patients with long-term leukemia chemotherapy diagnosed and treated in our hospital from July 2017 to October 2019 were enrolled and randomly assigned to observation and control groups using the random number table approach. Fifty-one patients in the control group received routine nursing, while 52 patients in the observation group received empathic nursing with mindfulness cognitive therapy. After three months of nursing care, cancer-induced fatigue was measured with the Piper Fatigue Scale (PFS), hope level with the Herth Hope Index (HHI), and negative emotion with the Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD). Self-management (Chinese Strategies Used by People to Promote Health) was also recorded. RESULTS: The observation group's total scores in behavior, cognition, emotion, feeling, and PFS were lower than the control group after the intervention (P < 0.05). Keeping close contact with others, the attitude of taking positive actions, the attitude toward reality and future, and the total HHI score were higher in the observation group than the control group (P < 0.05). The observation group's HAMA and HAMD scores were lower than the control group (P < 0.05). The observation group's positive attitude, self-decision, and self-relief scores were greater than the control group (P < 0.05). CONCLUSION: Empathetic nursing with cognitive mindfulness therapy is beneficial in improving cancer-related fatigue, negative emotions, expectation level, and self-management ability in patients with long-term leukemia chemotherapy.

Conservative oxygen therapy for critically ill patients: a meta-analysis of randomized controlled trials.

OBJECTIVE: Conservative oxygen strategy is recommended in acute illness while its benefit in ICU patients remains controversial. Therefore, we sought to conduct a systematic review and meta-analysis to examine such oxygen strategies' effect and safety in ICU patients. METHODS: We searched PubMed, Embase, and the Cochrane database from inception to Feb 15, 2021. Randomized controlled trials (RCTs) that compared a conservative oxygen strategy to a conventional strategy in critically ill patients were included. Results were expressed as mean difference (MD) and risk ratio (RR) with a 95% confidence interval (CI). The primary outcome was the longest follow-up mortality. Heterogeneity, sensitivity analysis, and publication bias were also investigated to test the robustness of the primary outcome. RESULTS: We included seven trials with a total of 5265 patients. In general, the conventional group had significantly higher SpO2 or PaO2 than that in the conservative group. No statistically significant differences were found in the longest follow-up mortality (RR, 1.03; 95% CI, 0.97-1.10; I2=18%; P=0.34) between the two oxygen strategies when pooling studies enrolling subjects with various degrees of hypoxemia. Further sensitivity analysis showed that ICU patients with mild-to-moderate hypoxemia (PaO2/FiO2 >100 mmHg) had significantly lower mortality (RR, 1.24; 95% CI, 1.05-1.46; I2=0%; P=0.01) when receiving conservative oxygen therapy. These findings were also confirmed in other study periods. Additional, secondary outcomes of the duration of mechanical ventilation, the length of stay in the ICU and hospital, change in sequential organ failure assessment score, and adverse events were comparable between the two strategies. CONCLUSIONS: Our findings indicate that conservative oxygen therapy strategy did not improve the prognosis of the overall ICU patients. The subgroup of ICU patients with mild to moderate hypoxemia might obtain prognosis benefit from such a strategy without affecting other critical clinical results.

Combined Influence of Insulin Resistance and Inflammatory Biomarkers on Type 2 Diabetes: A Population-based Prospective Cohort Study of Inner Mongolians in China.

This prospective study was designed to examine the combined influence of insulin resistance (IR) and inflammatory biomarker levels on type 2 diabetes mellitus (T2DM) among 1,903 Inner Mongolians. During follow-up, 205 (10.77%) participants developed T2DM, and the incidence of T2DM was higher among subjects with IR, elevated C-reactive protein (CRP), elevated sICAM-1, elevated sE-selectin, or the coexistences of IR with elevated CRP, elevated sICAM-1, elevated sE-selectin, and elevated angiotensin II (all P < 0.05) compared with patients without IR or any elevated biomarkers. In multivariate analysis, the odd ratios [OR, (95% confidence intervals)] for these conditions were 1.944 (1.405-2.691), 2.003 (1.449-2.767), 1.706 (1.232-2.362), 1.560 (1.123-2.165), 2.708 (1.809-4.054), 1.885 (1.155-3.078), 2.101 (1.340-3.295), and 2.260 (1.426-3.582), respectively. Our findings demonstrated that IR and elevated inflammatory biomarkers were associated with T2DM, and that the coexistence of IR and elevated inflammatory biomarkers increased the risk of T2DM.

PAI-1/PIAS3/Stat3/miR-34a forms a positive feedback loop to promote EMT-mediated metastasis through Stat3 signaling in Non-small cell lung cancer.

AIM: This study intented to clarify the intracellular effect of PAI-1 on Non-small cell lung cancer (NSCLC) metastasis and the precise mechanism involved. METHODS: The metastatic properties of NSCLC cells were determined by transwell assays and wound-healing assay in vitro. The mRNA and protein expressions of genes were analyzed by Real-time qPCR and western blot, respectively. Pulmonary metastasis model of NSCLC cells was established to evaluate the pro-metastasis effect of PAI-1 and anti-metastatic effect of miR-34a in vivo. The gene targets of miR-34a were confirmed by luciferase reporter assays. Chromatin immunoprecipitation assay was employed to detect the transcriptional regulation of miR-34a. Co-immunoprecipitation assay was performed to observe the interaction of proteins. RESULTS: PAI-1, which was elevated in NSCLC patients with recurrence and metastasis, augmented NSCLC metastasis and was negatively related to the prognosis of NSCLC. miR-34a, which was decreased in NSCLC patients with metastasis, attenuated NSCLC metastasis and was positively correlated with the prognosis of NSCLC. Moreover, PAI-1 was identified as the target gene of miR-34a and activated the Stat3 signaling pathway to promote epithelial-mesenchymal transition (EMT) in NSCLC cells. PAI-1 interacted with PIAS3 to regulate Stat3-dependent gene expression and miR-34a was transcriptionally suppressed by Stat3 to form a positive regulatory loop through Stat3 signaling. CONCLUSION: Our findings suggest that PAI-1 and miR-34a, which can be clinically utilized as biomarkers for the clinical prognosis or diagnosis of NSCLC, are potential targets for the treatment of NSCLC.

High mobility group box1 protein is involved in acute inflammation induced by Clostridium difficile toxin A.

High mobility group box1 (HMGB1), as a damage-associated inflammatory factor, contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, we explored the role of HMGB1 in CDI (Clostridium difficile infection) by in vivo and in vitro experiments. Our results showed that HMGB1 might play an important role in the acute inflammatory responses to C. difficile toxin A (TcdA), affect early inflammatory factors, and induce inflammation via the HMGB1-TLR4 pathway. Our study provides the essential information for better understanding the molecular mechanisms of CDI and the potential new therapeutic strategies for the treatment of this infection.

Infundibular dilation: an anatomical variant or a pre-aneurysm? Advantages of assessment with three-dimensional rotational angiography.

PURPOSE: Whether an infundibular dilation (ID) is an anatomical variant or a pre-aneurysm has not been clearly determined. The aim of the present study was to evaluate the anatomical change of IDs by use of three-dimensional rotational angiography (3DRA) with volume rendering (VR). METHODS: One-hundred thirty-eight patients with known or suspected aneurysms, treated consecutively, underwent both two-dimensional digital subtraction angiography (2DDSA) and 3DRA with VR. Two readers evaluated the IDs or aneurysms blindly, using 2DDSA and 3DRA, according to the same diagnostic criteria. A 5-point scale of observer confidence was used to determine the presence of IDs or aneurysms. For 3DRA with VR, the relationship between IDs and aneurysms was classified as one of the three types: type I, protrusion or bulge from side wall of IDs; type II, aneurysms involving or enclosing IDs; or type III, aneurysms and IDs coexisting near each other but with some distance between them. RESULTS: The number of IDs found by 2DDSA and 3DRA with VR was 41 and 48, respectively. Five anterior choroidal arteries and two posterior communicating arteries IDs were missed by 2DDSA. According to 3DRA with VR, there were five IDs of type I, nine of type II, and 22 of type III. CONCLUSIONS: The 3DRA with VR appears superior to 2DRA for both diagnosing IDs and displaying the anatomical relationship between IDs and aneurysms. The findings also suggest that some IDs might progress to aneurysms or become a part of them, which should be carefully evaluated prior to operation.

3D rotational angiography with volume rendering: the utility in the detection of intracranial aneurysms.

AIMS: The advent of three-dimensional (3D) rotational angiography (3D DSA) challenged the role of digital subtraction angiography (DSA) as a "gold standard" in the diagnosis of intracranial aneurysms. In this study, we report our experiences in diagnosing intracranial aneurysms by using 3D DSA with volume rendering (VR) technique, particularly focusing on its role in depicting additional aneurysms missed by 2D DSA. MATERIALS AND METHODS: One hundred and thirty-eight consecutive patients with known or suspected aneurysms (54 men, 84 women; median age, 55 years; age range, 18-83 years) underwent both conventional DSA and 3D DSA with VR examination simultaneously. The images of 2D DSA or 3D DSA with VR were evaluated by two observers independently for the presence of aneurysms. Then additional aneurysms were decided and depicted. RESULTS: 3D DSA with VR showed 146 aneurysms in 123 (89.1%) of 138 patients and no aneurysms in 15 patients. 2D DSA showed 115 aneurysms in 110 of 137 patients, with one aneurysm in 106 patients each, 2 in 3 patients each and 3 in 1 patient. After reaching a consensus, there were 31 additional aneurysms detected by 3D DSA with VR. 30 aneurysms were <3 mm in maximum diameter with 3 aneurysms ruptured. These additional aneurysms were located in internal carotid artery (ICA, n = 28, 90.32%), anterior cerebral artery (ACA, n = 3, 9.68%). No additional aneurysms were found in either middle cerebral artery (MCA) or vertebrobasilar and posterior cerebral artery (PCA) systems. CONCLUSIONS: 3D DSA, especially VR images, not only clearly reveals aneurysms and aneurysmal morphology, but also detects additional aneurysms missed by 2D DSA, especially small aneurysms less than 3 mm.

[An investigation of changes in gene expression profile of heart tissue in a rat sepsis model].

OBJECTIVE: To investigate the changes in gene expression spectrum of heart tissue in septic rats by DNA microarrays. METHODS: Thirty male Wistar rats were randomly divided into sepsis group and control group with 15 rats in each group. Cecal ligation and puncture (CLP) was used to reproduce rat sepsis model, and the success of reproduction was confirmed by examining the heart tissue with transmission electron microscope. Gene expression spectrum was studied with oligonucleotide gene expression profile microarray that contained 22 523 rat cDNA clones to detect the changes in gene expression pattern of rat heart tissue 24 hours after CLP. Genes with fluorescent signal of Cy3/Cy5 of ratio average (RA)>2.0 or RA<0.5 were identified as differential genes, then those that high correlated to sepsis were screened by means of related computer software, and their relationship was analyzed. RESULTS: Electron microscopic examination of heart tissue demonstrated that the sepsis model was successfully reproduced. Compared to the controls, gene expression of 418 genes of heart tissue of septic rat were changed 24 hours after CLP, accounting for 1.86%, and among them 200 genes showed up-regulation, 218 genes with down-regulation. Among known functional genes, 84 genes up-regulated and 74 genes down-regulated. They were related with a range of genetic functions, such as acute stress reaction, signal transduction, immune response, energy metabolism related genes etc. CONCLUSION: There are a series of changes in gene expression in heart tissue apparently induced by sepsis rat. DNA microarray technology provides a new tool for rapidly analyzing them.

[Titin gene mutations in Chinese patients with dilated cardiomyopathy].

OBJECTIVE: Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions. Four possible disease-associated mutations located in three exons (3, 14, 49) of titin gene (TTN) have been identified in Japanese DCM patients in 2002. We observed the possible association of TTN mutation in Chinese patients with DCM. METHODS: Three exons of TTN (3, 14, 49) were screened in 117 DCM patients and 120 controls by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and DNA sequence. SSCP was carried out following a protocol optimized for each PCR fragment after amplification. Abnormal SSCP results were subsequently confirmed by DNA sequencing. RESULTS: The mutations reported in Japanese DCM patients were not identified in this patient cohort. A novel mutation [the G13053A (TTN cDNA sequence, X90568) change resulted in amino acid change at position 4351 (Gly4351Asp)] was found in two young DCM patients from a DCM family (1.7%). There was no similar mutation in controls. CONCLUSION: This novel Gly4351Asp mutation in TTN might be associated with DCM.

Genetic polymorphisms of the DNA repair gene and risk of nasopharyngeal carcinoma.

CONTEXT: X-ray repair cross-complementing groups 1 and 3 (XRCC1 and XRCC3) and xeroderma pigmentosum group D (XPD) are mainly involved in base excision repair, homologous recombination repair, and nucleotide excision repair of DNA repair pathways, respectively. Previous studies have demonstrated that their gene polymorphisms were associated with some cancer susceptibility. OBJECTIVE AND DESIGN: To investigate the effect of XPD Lys751Gln, XRCC1 Arg399Gln, Arg194Trp, Arg280His, and XRCC3 Thr241Met polymorphisms on the risk of nasopharyngeal carcinoma (NPC), a population-based case-control study of 153 NPC patients and 168 healthy controls among Sichuan population was conducted. RESULTS: Our results showed that XRCC1 codon 194 Trp allele was associated with an increased risk of NPC (odds ratio [OR] = 1.828, 95% confidence interval [CI]: 1.286-2.598), and XPD codon 751Gln allele was associated with a borderline decrease of NPC (OR = 0.600, 95% CI: 0.361-1.000); combination analysis showed that individuals with both putative genotypes of XPD codon 751 Lys/Lys and XRCC1 codon 194 Arg/Trp or Trp/Trp have a significantly elevated risk of NPC (OR = 2.708, 95% CI: 1.338-5.478). CONCLUSION: The results indicated that XRCC1 codon 194 Trp allele and XPD codon 751 Lys allele may be contributing factors in the risk of NPC.

[Induction of hypoxia-inducible factor-1alpha in two kinds of rats asphyxiation death models].

OBJECTIVE: To investigate the expression of hypoxia-inducible factor 1-alpha (HIF1-alpha) in the heart, lung, liver and kidney in rats died of two typical models of asphyxia. METHODS: Two asphyxia models were made and tissue samples of the dead rats were collected from different groups at various postmortem duration. The expression and the changes of HIF1-alpha in various tissues were examined by immunohistochemistry and image analysis techniques. Results Significant expression of HIF1-alpha was observed in the myocardial fibers, kidney cells, liver cells and lung cells in both asphyxia models, but not in the control group. The expression of HIF1-alpha in various tissues in the rat died of nitrogen gas breathing was found in the nuclei at 0 hour and the expression level decreased gradually thereafter. The HIF1-alpha expression level and duration in various tissues of the rat died of hanging were higher and longer than that of the former group, with a peak of the expression level observed 6 hours after death, and then started to decline in all tissues except the heart where the expression still showed an increase 24 hours after death. The control groups showed a steady expression in the cytoplasm but not in the nuclei. CONCLUSION: HIF1-alpha appears to be a valuable biomarker in the diagnosis of asphyxia within 24 hours after death.

[Multiplexed mutagenically separated PCR assay for rapid detection of SNP loci in mitochondrial DNA coding region].

OBJECTIVE: To develop a multiplexed mutagenically separated PCR (MS-PCR) for single nucleotide polymorphism (SNP) loci typing in mitochondrial DNA coding regions and to study the applications in investigating the allele frequencies and haplotypes of four SNP loci in mitochondrial DNA coding regions in Chinese Chengdu Han population. METHODS: Four SNP loci C12705T, A8701G, G8584A and C10400T, two allele specific forward primer with 4 bases different in size and a common reverse primer were designed for SNP typing. The primers simultaneously were amplified in a single tube. The genotyping of SNPs was determined by the two allele specific fragments different in size after polyacrylamide gel and silver staining. RESULTS: The different SNP loci comprised a single band with different size respectively. Typing results were completely consistent with those by direct sequencing. The allelic frequencies of C12705T, A8701G, G8584A and C10400T were 0.3813/0.6187, 0.4813/0.5187, 0.8250/0.1750 and 0.4938/0.5062 respectively. A total of 6 different haplotypes was identified and the genetic diversity reached 0.7137. CONCLUSION: Multiplexed MS-PCR is a simple, rapid, accurate and efficient method for SNP typing, which will be very powerful for SNPs in the database establishing of mitochondrial DNA coding regions, the testing of forensic and population genetics research.

[Expression of HIF1-alpha on myocardium and lung in rats model of asphyxia death].

OBJECTIVE: To investigate the expression of HIF1-alpha in heart and lung tissue died from asphyxia. METHODS: The rats model of asphyxia death was constructed by hanging, different asphyxia groups and control group sets were made according the postmortem time (0,2,6,24 h), immunohistochemistry and half-quantitative RT-PCR methods were used to investigate expression of HIF1-alpha and mRNA changes on heart and lung tissue. RESULTS: The positive staining of HIF1-alpha could be observed in the myocardium and lung tissue. Significant differences were found between the groups of asphyxia and their corresponding control group. HIF1-alpha expression was found in all the asphyxia groups while it was only expressed in the control groups of 2 h, 6 h and 24 h. Nucleic positive staining could be detected in all the asphyxia groups but none was found in the control groups. RT-PCR showed that the expression of mRNA between 0 h asphyxia group and 0 h control group were equal in both cardic muscle and lung, but elevated expression in groups of 2,6,24h compared to their control groups. CONCLUSION: The nuclear positive staining of HIF1-alpha in heart and lung can be a special character of suffocation death.