Construction of an Injectable Composite Double-Network Hydrogel as a Liquid Embolic Agent.

Conventional embolists disreputably tend to recanalization arising from the low filling ratio due to their rigidity or instability. As a result, intelligent hydrogels with a tunable modulus may meaningfully improve the therapeutic efficacy. Herein, an injectable composite double-network (CDN) hydrogel with high shear responsibility was prepared as a liquid embolic agent by cross-linking poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMC) via dynamic covalent bonding of borate ester and benzoic-imine. A two-dimensional nanosheet, i.e., layered double hydroxide (LDH), was incorporated into the network through physical interactions which led to serious reduction of yield stress for the injection of the hydrogel and the capacity for loading therapeutic agents like indocyanine green (ICG) and doxorubicin (DOX) for the functions of photothermal therapy (PTT) and chemotherapy. The CDN hydrogel could thus be transported through a thin catheter and further in situ strengthened under physiological conditions, like in blood, by secondarily cross-linking with phosphate ions for longer degradation duration and better mechanical property. These characteristics met the requirements of arterial interventional embolization, which was demonstrated by renal embolism operation on rabbits, and meanwhile favored the inhibition of subcutaneous tumor growth on an animal model. Therefore, this work makes a breakthrough in the case of largely reducing the embolism risks, thus affording a novel generation for interventional embolization.

[Applying the Concept of Grief Counseling in Caring for an Elderly Dialysis Patient With Bereavement Due to the Death of Spouse: A Nursing Care Experience].

This article describes a 76-year-old dialysis patient who experienced widowhood. The nursing intervention occurred between April 2nd to June 28th, 2015. Using observation, interviews, medical records and health examinations, the authors assessed the patient's physical, psychological, social, intellectual, and spiritual status. The patient not only presented poor appetite, insomnia, hopelessness, and grief but had also attempted suicide. Thus, three health problems were identified, including dysfunctional grieving, hopelessness, and sleep pattern disturbance. Employing caring, active listening, and empathy, we helped the patient achieve the four tasks of Worden's Mourning: (1) to accept the reality of loss; (2) to work through the pain of grief; (3) to adjust to an environment in which the deceased is missing; and (4) to emotionally relocate the deceased and move on with life. With comprehensive and persistent nursing intervention, the patient got the support from her family members and eventually readapted to life without the deceased and continued to take hemodialysis and found new life motivation.

The Effect of Traditional Chinese Medicine on Postviral Olfactory Dysfunction: A Systematic Review and Meta-Analysis.

Objective: The aim of this study is to evaluate the efficacy and safety of traditional Chinese medicine (TCM) for postviral olfactory dysfunction (PVOD). Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical (CBM) Database, and Wanfang Database were electronically searched from their inception to July 25, 2022. Two authors independently performed study selection, data extraction, and quality assessment to ensure systematic quality evaluation. Randomized controlled trials (RCTs) comparing TCM with olfactory training and/or drug therapy (OTDT) were included. The outcomes were the effective rate, QOD-P, TDI score, UPSIT score, and adverse effects. Cochrane RoB was the guideline used to evaluate the methodological quality of the included trials. RevMan 5.3 software was used for statistical analysis. Results: A total of 6 RCTs involving 467 patients with PVOD were selected. Compared with OTDT, TCM plus OTDT decreased QOD-P (MD = -1.73, 95% CI (-2.40, -1.06), P < 0.0001) but did not increase the effective rate (T&T) (RR = 1.28, 95% CI (0.86, 1.90), P=0.22, I 2 = 61%). Compared with no treatment, TCM seemed to increase the treatment success rate (UPSIT) (RR = 3.17, 95% CI (1.78, 5.65), P < 0.0001, I 2 = 0%), but there was no statistically significant difference in improving the UPSIT score (MD = 3.44, 95% CI (-1.36, 8.24), P=0.16). Compared with drug therapy, TCM plus drug therapy appeared to increase the effective rate (ΔVAS) (RR = 2.36, 95% CI (1.41, 3.94), I 2 = 0%), but there was no statistically significant difference in improving the TDI score (MD = 2.10, 95% CI (-1.99, 6.19), P=0.31). No significant differences in adverse reactions were reported between TCM and OTDT. Conclusion: TCM may be an effective treatment for PVOD. With a lack of high-quality RCTs, further large-scale and high-quality RCTs are still warranted.

Comprehensive analysis of resistance mechanisms to EGFR-TKIs and establishment and validation of prognostic model.

PURPOSE: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for patients with lung adenocarcinoma (LUAD) harboring activating EGFR mutations. However, the emergence of drug resistance to EGFR-TKIs remains a critical obstacle for successful treatment and is associated with poor patient outcomes. The overarching objective of this study is to apply bioinformatics tools to gain insights into the mechanisms underlying resistance to EGFR-TKIs and develop a robust predictive model. METHODS: The genes associated with gefitinib resistance in the LUAD cell Gene Expression Omnibus (GEO) database were identified using gene chip expression data. Functional enrichment analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed to comprehensively explore the mechanism of gefitinib resistance. Furthermore, a GRRG_score was constructed by integrating genes related to LUAD prognosis from The Cancer Genome Atlas (TCGA) database with the screened Gefitinib Resistant Related differentially expressed genes (GRRDEGs) using the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. Furthermore, we conducted an in-depth analysis of the tumor microenvironment (TME) features and their association with immune infiltration between different GRRG_score groups. A prognostic model for LUAD was developed based on the GRRG_score and validated. The HPA database was used to validate protein expression. The CTR-DB database was utilized to validate the results of drug therapy prediction based on the relevant genes. RESULTS: A total of 110 differentially expression genes were identified. Pathway enrichment analysis of DEGs showed that the differentially expressed genes were mainly enriched in Mucin type O-glycan biosynthesis, Cytokine-cytokine receptor interaction, Sphingolipid metabolism. Gene set enrichment analysis showed that biological processes strongly correlated with gefitinib resistance were cell proliferation and immune-related pathways, EPITHELIAL_MESENCHYMAL_TRANSITION, APICAL_SURFACE, and APICAL_JUNCTION were highly expressed in the drug-resistant group; KRAS_SIGNALING_DN, HYPOXIA, and HEDGEHOG_SIGNALING were highly expressed in the drug-resistant group. The GRRG_score was constructed based on the expression levels of 13 genes, including HSPA2, ATP8B3, SPOCK1, EIF6, NUP62CL, BCAR3, PCSK9, NT5E, FLNC, KRT8, FSCN1, ANGPTL4, and ID1. We further screened and validated two key genes, namely, NUP62CL and KRT8, which exhibited predictive value for both prognosis and drug resistance. CONCLUSIONS: Our study identified several novel GRRDEGs and provided insight into the underlying mechanisms of gefitinib resistance in LUAD. Our results have implications for developing more effective treatment strategies and prognostic models for LUAD patients.

Liver cirrhosis and risk of intracerebral hemorrhage: a 9-year follow-up study.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the risk of future intracerebral hemorrhage development in patients with liver cirrhosis. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study cohort included 948 patients with liver cirrhosis diagnosed in 1999 and 9480 age- and sex-matched patients of the same year. All patients were tracked from their index visits for 9 years. RESULTS: Intracerebral hemorrhage developed in 1.3% of patients with liver cirrhosis and 1.0% of patients in the comparison cohort during the follow-up period. Log-rank test analysis showed no significant difference between the 2 cohorts (P=0.39). A stratified Cox proportional regression model showed an adjusted hazard ratio of 1.62 (95% CI, 0.85 to 3.10) for patients with liver cirrhosis to develop intracerebral hemorrhage compared with patients without liver cirrhosis. CONCLUSIONS: Patients with liver cirrhosis had a similar intracerebral hemorrhage incidence rate but a trend of increased risk for intracerebral hemorrhage compared with the comparison cohort during the 9-year follow-up period.

The effect of traditional Chinese medicine treatment for post-viral olfactory dysfunction: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-viral olfactory dysfunction (PVOD) have been reported in infections caused by several respiratory viruses, especially in COVID-19 which influence severely the quality of life of affected subjects. Few study has been published on the treatment of PVOD. Traditional Chinese medicine (TCM) is an effective method for PVOD which effects and safety have been confirmed. Therefore, this study is aim to evaluate the effects of TCM on PVOD. METHODS: A searching strategy will be carried out mainly in the following databases in English and Chinese, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical Database (CBM), and Wanfang Database. Only randomized controlled trials related to TCM for PVOD will be included to enhance effectiveness. The primary outcome is the effective rate of PVOD. The secondary outcomes are included olfactory domain value examination, visual analogue scale (VAS), questionnaires of olfactory disorders (QOD), T&T olfactometer test, Sniffin ticks test, and any other clinical assessments. Two authors will independently perform study selection, data extraction, and quality assessment to ensure the quality of the systematic evaluation. Every disagreement will be deal with by the third author. Data synthesis and subgroup analysis will be performed in the Review Manager V 5.3.3. RESULTS: This study is aim to evaluate the efficacy and safety of TCM in PVOD. CONCLUSION: : This meta-analysis may provide more reliable evidence-based medical evidence for clinical practice to assist patient in relieving PVOD. ETHICS AND DISSEMINATION: There is no need to acquire ethical approval for individuals come from literatures instead of recruiting directly. The findings of this review will be reported in peer-reviewed publications and/or presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021238977.

Identification of Hub Genes and Small Molecule Drugs Associated with Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer.

Targeting EGFR, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), brings lights to the treatment of non-small cell lung cancer (NSCLC). Although T790M mutation responded as one of the main reasons of acquired resistance, still 15% of the resistance patients can't be explained by the known mechanisms. The purpose of this research was to identify some new mechanisms of gefitinib acquired resistance, and to predict small molecules drugs which may reverse drug resistance by integrated bioinformatics analysis. The GSE34228 data package containing the microarray data of acquired gefitinib-resistant cell line (PC9GR) and gefitinib-sensitive cell line (PC9) from the GEO database were downloaded, and gene co-expression networks by weighted gene co-expression network analysis (WGCNA) were constructed to identified key modules and key genes related to gefitinib resistance. Furthermore, the significantly differentially expressed genes (DEGs) between the two cell types were screened out, and a protein-protein interaction (PPI) network to obtain the key genes of DEGs was accordingly constructed. Through the above two methods, 4 hub genes, PI3, S100A8, AXL and PNPLA4 were mined as the most relevant to gefitinib resistance. Among them, PI3, S100A8 were down-regulated in PC9GR cell samples, while AXL, PNPLA4 were up-regulated. The gene set enrichment analysis (GSEA) for single gene showed that the four hub genes were mainly correlated with cell proliferation and cycle. Besides, small molecule drugs with the potential to overcome resistance, such as Emetine and cephaeline, were screened by CMap database. Consistent with this, in vitro experiments results have shown that emetine and cephaeline can increase the sensitivity of drug-resistant cells to gefitinib, and the mechanism may be related to the regulation of PI3 and S100A8. In conclusion, 4 hub genes were found to be related to the occurrence of gefitinib resistance in non-small cell lung cancer, and several small molecule drugs were screened out as potential therapeutic agents to overcome gefitinib resistance, which may lead a new way for the treatment of NSCLC of acquired resistance to gefitinib.

Cardiac cephalalgia presented with a thunderclap headache and an isolated exertional headache: report of 2 cases.

Headache could be the only manifestation of a myocardial infarction or angina pectoris. The recognition of myocardial ischemia as the cause of headache is important in clinical practice. We report two cases of cardiac cephalalgia, defined as headache attributed to myocardial ischemia. The first patient presented with a thunderclap headache probably secondary to a myocardial ischemia and the second patient presented with isolated headaches secondary to angina pectoris triggered by exertions. The clinical presentations of cardiac cephalalgia are highly variable and the most consistent feature is severe in intensity. Cardiac cephalalgia should be considered one of the differential diagnoses of exertional headache and thunderclap headache when the patient is older or has cardiovascular risk factors.

Surface Modification of FeCoNiCr Medium-Entropy Alloy (MEA) Using Octadecyltrichlorosilane and Atmospheric-Pressure Plasma Jet.

Surface condition and corrosion resistance are major concerns when metallic materials are going to be utilized for applications. In this study, FeCoNiCr medium-entropy alloy (MEA) is first treated with a nitrogen atmospheric-pressure plasma jet (APPJ) and then coated with octadecyltrichlorosilane (OTS) for the surface modification. The hydrophobicity of the FeCoNiCr MEA was effectively improved by OTS-coating treatment, APPJ treatment, or the combination of both treatments (OTS-coated APPJ-treated), which increased the water contact angle from 54.49° of the bare MEA to 70.56°, 93.94°, and 88.42°, respectively. Potentiodynamic polarization and electrochemical impedance spectroscopy tests demonstrate that the APPJ-treated FeCoNiCr MEA exhibits the best anti-corrosion properties. X-ray photoelectron spectroscopy reveals that APPJ treatment at 700 °C oxidizes all the alloying elements in the FeCoNiCr MEA, which demonstrates that a short APPJ treatment of two-minute is effective in forming a metal oxide layer on the surface to improve the corrosion resistance of FeCoNiCr MEA. These results provide a convenient and rapid method for improving surface properties of FeCoNiCr MEA.

Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer. METHODS: A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS). RESULTS: Compared to the SA group, the TA group didn't show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study. CONCLUSION: Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.

Risk of peripheral edema in cancer patients treated with MEK inhibitors: a systematic review and meta-analysis of clinical trials.

BACKGROUND: MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors. MATERIALS AND METHODS: The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau2, Chi2, and I2 analyses. RESULTS: A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR = 3.05, 95% CI = 1.98-4.70; p < .00001), but the MEK inhibitors (Trametinib and Selumetinib) did not increase the risk of high grade edema (RR = 1.88, 95% CI = 0.66-5.35; p = .24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p = .03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved. CONCLUSION: This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.

Elevated heparanase expression is associated with poor prognosis in breast cancer: a study based on systematic review and TCGA data.

Heparanase promotes tumorigenesis, angiogenesis, and metastasis. Here, we conducted a study based on systematic review and the Cancer Genome Atlas (TCGA) data that examined heparanase expression in clinical samples to determine its prognostic value. According to the meta-analysis and TCGA data, we found that heparanase expression was up-regulated in most breast cancer specimens, and elevated heparanase expression was associated with increased lymph node metastasis, larger tumor size, higher histological grade, and poor survival. These results suggest that targeting heparanase might improve treatments for breast cancer patients.

Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis.

Chinese herbal medicine (CHM) has been increasingly employed during therapy for breast cancer, but its efficacy remains a matter of debate. This systematic review examined randomized controlled trials to provide a critical evaluation of this treatment. The results demonstrated that the combined use of CHM with chemotherapy may improve the immediate tumor response and reduce chemotherapy-associated adverse events. Our findings highlight the poor quality of Chinese studies, and additional well-designed randomized controlled trials addressing the role of CHM are warranted. The lack of molecular-based evidence for CHM and Zheng has resulted in a limited understanding and acceptance of CHM and traditional Chinese medicine in Western countries. We believe that researchers should immediately explore a CHM-based cure, and CHM should be applied to routine care as soon as conclusive data are available.

Parkinson's disease and risk of hip fracture: an 8-year follow-up study in Taiwan.

BACKGROUND: Patients with Parkinson's disease (PD) are subject to posture instability and falling. However, PD was not included as one of the risk factors in commonly used fracture risk calculation tools and the fracture rate in patients with PD was rarely reported. The aim of this study was to evaluate the risk of hip fracture in patients with PD. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 394 patients with PD diagnosed in 1999-2000. The comparison cohort was comprised of 3940 age- and sex-matched patients from the same enrollment period. All patients were tracked from their index visits for eight years. RESULTS: Hip fracture developed in 10.4% of patients with PD and 4.1% of patients in the comparison cohort during the follow-up period. Log-rank test analysis showed a significantly higher rate of hip fracture in PD. The Cox proportional regression model showed an adjusted hazard ratio of 2.71 (95% confidence interval = 1.92-3.83, P < 0.001) for patients with PD. CONCLUSION: The hip fracture rate was as high as 10.4% in PD patients during 8 years follow-up period. While assessing the risk of hip fracture, PD should be taken into consideration. For those very high risk patients (elderly women with PD, osteoporosis, diabetes and diabetic neuropathy), many efforts should be made to prevent fracture.

The incidence rate of post-stroke epilepsy: a 5-year follow-up study in Taiwan.

PURPOSE: The impact of epilepsy following different subtypes of stroke is unclear. The aim of this study was to evaluate the risk of post-stroke epilepsy with different stroke subtypes. METHODS: A total of 4126 stroke patients and 24,756 age- and sex-matched controls were retrieved from the Longitudinal Health Insurance Database 2005, a major dataset of the National Health Insurance Research Database, from 2000 to 2003. All were then individually tracked to their last medical visit up to five years from 30 days after their first-ever stroke incident to identify those who developed epilepsy. RESULTS: Among the 4126 stroke patients, 72.2% had ischemic stroke, 14.7% had intracerebral hemorrhage (ICH), 2.3% had subarachnoid hemorrhage (SAH), 2.0% had other and unspecified intracranial hemorrhage (OIH), including subdural hemorrhage and epidural hemorrhage, and 8.9% had multiple stroke subtypes. The adjusted hazard ratio for the development of epilepsy was 11.5 (95% CI 8.2-16.2) for the patients with stroke compared to the controls. 2.6% of the patients with stroke developed epilepsy during the 5-year follow-up period. The rate of post-stroke epilepsy was highest in patients with multiple subtypes (7.7%), followed by ICH (4.3%), SAH (4.2%), OIH (2.5%) and ischemic stroke (1.6%). CONCLUSION: Stroke patients had a significantly higher risk of developing epilepsy than the controls. The risk of post-stroke epilepsy was higher in patients with hemorrhagic stroke than ischemic stroke.

Newly diagnosed type 2 diabetes and risk of dementia: a population-based 7-year follow-up study in Taiwan.

BACKGROUND: Diabetes is associated with an increased risk of developing dementia. However, data on the patients with newly diagnosed type 2 diabetes are limited. OBJECTIVE: To investigate the relationship between newly diagnosed type 2 diabetes and the risk of developing dementia, ischemic stroke and intracranial hemorrhage after disease diagnosis and the interrelationship between dementia and the stroke events. METHOD: Data were collected from the National Health Insurance Research Database of Taiwan. The study cohort included 3717 patients newly diagnosed with type 2 diabetes and 37,170 age- and sex-matched comparison patients from the same period. All patients were tracked for 7 years following their index visit in 2000-2001. RESULT: After adjusting for potential confounders, dementia risk was approximately 63% higher (hazard ratio [HR], 1.63; 95% CI, 1.33-1.99) among newly diagnosed type 2 diabetic patients than among comparison subjects. Newly diagnosed type 2 diabetes also increased the risk of developing ischemic stroke but not intracranial hemorrhage. About 43.6% of diabetic patients who developed dementia also had ischemic stroke during the follow-up period, higher than the rate 29.6% in the comparison group. CONCLUSION: This study shows that newly diagnosed type 2 diabetes is associated with a 63% higher future risk of dementia during the 7-year follow-up period. The high dementia and ischemic stroke overlap rate in the diabetic study group suggests vascular events play an important role in the pathogenesis of developing dementia.