Systemic chemotherapy plus transarterial chemoembolization versus systemic chemotherapy alone for unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study.

PURPOSE: Systemic chemotherapy (SYS) is the first-line treatment of unresectable intrahepatic cholangiocarcinoma (ICC). However, the survival benefit of SYS is still limited. This study compared the efficacy and safety of patients with unresectable ICC treated with transarterial chemoembolization (TACE) plus SYS to SYS alone. MATERIAL AND METHODS: The multicenter retrospective cohort study included patients aged ≥ 18 years old with pathologically diagnosed ICC. Patients with unmeasurable lesions, not receiving SYS treatment, Child-Pugh grade C, Eastern Cooperative Oncology Group performance status score of 3 or higher, prior liver resection, incomplete medical information, or discontinuation of the first SYS treatment were excluded. Data collection was mainly from the hospital system, and the survival outcome of patients was obtained through follow-up. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Propensity score matching at a 1:1 ratio using the nearest neighbor matching algorithm was performed to reduce selection bias between the TACE plus SYS and SYS alone groups. The Cox proportional hazards model was used to identify prognostic factors associated with OS and to estimate their hazard ratios. Modified Response Evaluation Criteria in Solid Tumors criteria were utilized to evaluate the response of tumors to therapy. RESULTS: Between June 2016 and February 2023, 118 unresectable ICC patients from three hospitals were included in this study. Of them, 37 were in the TACE plus SYS group and 81 were in the SYS alone group. The median OS in the combination group was 11.3 months, longer than the 6.4 months in the SYS alone group (P = 0.011). A greater objective response rate (ORR) and disease control rate (DCR) were observed in the combination group than in the SYS alone group (ORR, 48.65 vs. 6.17%, P < 0.001; DCR, 89.19 vs. 62.96%, P = 0.004). There were 16 patients in each group after matching, and the matched results remained consistent regarding OS and tumor response. Adverse events (AEs) were similar in the two groups after matching. CONCLUSION: Compared to SYS alone, the combination treatment of TACE plus SYS was more effective than SYS alone in improving OS, ORR, and DCR without any significant increase in AEs. TACE plus SYS may be a viable treatment option for patients with unresectable ICC.

Endoplasmic reticulum stress: a vital process and potential therapeutic target in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a chronic and progressive disease characterized by persistent respiratory symptoms and progressive airflow obstruction, has attracted extensive attention due to its high morbidity and mortality. Although the understanding of the pathogenesis of COPD has gradually increased because of increasing evidence, many questions regarding the mechanisms involved in COPD progression and its deleterious effects remain unanswered. Recent advances have shown the potential functions of endoplasmic reticulum (ER) stress in causing airway inflammation, emphasizing the vital role of unfolded protein response (UPR) pathways in the development of COPD. METHODS: A comprehensive search of major databases including PubMed, Scopus, and Web of Science was conducted to retrieve original research articles and reviews related to ER stress, UPR, and COPD. RESULTS: The common causes of COPD, namely cigarette smoke (CS) and air pollutants, induce ER stress through the generation of reactive oxygen species (ROS). UPR promotes mucus secretion and further plays a dual role in the cell apoptosis-autophagy axis in the development of COPD. Existing drug research has indicated the potential of UPR as a therapeutic target for COPD. CONCLUSIONS: ER stress and UPR activation play significant roles in the etiology, pathogenesis, and treatment of COPD and discuss whether related genes can be used as biomarkers and therapeutic targets.

Rates of perceived medical errors and its correlation with work-related factors and personal distress among emergency physicians in China: a national cross-sectional study.

PURPOSE: Medical errors are a global concern, and specifically, EDs are at considerable risk for medical errors. Few studies focus on the healthcare provider's self-perceived medical errors in hospitals, let alone the ED. Hence, this study explored perceived medical errors and their correlation with work-related factors and personal distress among physicians in EDs in China. METHODS: From July 2018 to August 2018, a national web-based cross-sectional study was conducted. The link to the web-based questionnaire was posted on the emergency physicians' working platform, inviting Chinese licensed emergency physicians to participate anonymously in this survey. Our outcome of interest, medical errors, was investigated using self-reporting methods. Occupational stress was assessed using the Chinese version of the Effort-Reward Imbalance scale. The Patient Health Questionnaire, the subscale of the 10-item Positive and Negative Affect Schedule, the subscale of the validated Leiden Quality of Work Questionnaire and the 10-item Generalised Self-efficacy Scale were used to assess personal distress. Logistic regression analysis was used to determine factors significantly associated with perceived medical errors. RESULTS: A sample of 10 457 emergency physicians completed the survey. Almost half (43.63%) of physicians reported self-perceived medical errors during the previous 3 months. The rate of workplace verbal aggression, effort-reward imbalance and depressive symptoms were 81.81%, 78.39% and 35.71%, respectively. Medical errors were more likely to be reported among chief physicians, and those who reported the department was short-staffed for physicians, and who experienced workplace verbal aggression and intense work stress. Medical errors were significantly associated with negative affect and lower self-efficacy. CONCLUSION: Self-perceived medical errors are prevalent among physicians working in EDs and are associated with their workplace environment and personal distress. Targeted interventions are required to reduce physicians' workload and improve their working environment. Accounting for healthcare providers' distress is imperative for reducing the incidence of medical errors and improving their health.

Occurrence of self-perceived medical errors and its related influencing factors among emergency department nurses.

AIMS AND OBJECTIVES: To determine the prevalence and the associated factors of self-perceived medical errors among Chinese emergency department nurses. BACKGROUND: The emergency department is a place with a high incidence of medical errors. Studies about the occurrence and related influencing factors of medical errors among emergency nurses in China are very insufficient. DESIGN: A nationwide cross-sectional study. METHODS: A nationwide cross-sectional study was conducted from July 2018-August 2018. A total of 17,582 emergency department nurses from 31 provinces across China were eventually included in the analysis. Logistic regression is applied to examine the association of the independent variables with the perceived medical errors. The reporting of this study was compliant with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies. RESULTS: Of 17,582 participating nurses, 4445 (25.28%) reported self-perceived medical errors in the past 3 months. Nurses who were serving as nurses-in-charge; who reported fair or bad physical health; who reported staff shortage; who were exposed to more verbal abuse at work; who experienced effort-reward imbalance; who reported more over-commitment; or who had depressive symptoms were more likely to report medical errors. Older age and female gender were protective factors. CONCLUSIONS: In this study, a quarter of the emergency nurses reported that they had made medical errors in the past 3 months. Self-perceived medical errors are associated with multiple domains of work-related factors and personal distress. Feasible measures should be taken to reduce nurses' workload, improve their working environment, monitor and minimise the occurrence of medical errors among emergency department nurses. RELEVANCE TO CLINICAL PRACTICE: Emergency nurses, who are the most frequently in contact with patients, play an important role in identifying risk factors and preventing medical errors. Identifying risk factors that may lead to medical errors in the medical environment from both internal and external aspects will help nursing practitioners, hospital administrators and policy makers to take timely preventive measures to reduce the occurrence of medical errors and reduce harm to patients.

Evaluating effort-reward imbalance among nurses in emergency departments: a cross-sectional study in China.

BACKGROUND: Effort-reward imbalance is an adverse psychological response to working conditions that has several negative effects on nurses. However, there is little research on effort-reward imbalance and its influencing factors among nurses in emergency departments. This study aimed to understand the current situation of effort-reward imbalance and explore its influencing factors among emergency department nurses in China. METHODS: From July to August 2018, a structured online questionnaire survey was conducted among emergency department nurses in China. Data were collected from emergency department nurses employed in hospitals providing pre-hospital care in China. The questionnaire consisted of sociodemographic characteristics, work-related factors and effort-reward imbalance. A descriptive analysis and a binary logistic regression were conducted to explore the effort-reward imbalance and its influencing factors among emergency department nurses. RESULTS: The study involved 17,582 emergency department nurses; notably, the prevalence of effort-reward imbalance was 59.66%. The participating nurses who were males, aged 25 to 34 years, whose educational level was a bachelor degree or above, who had a junior or above title, who had longer years of service, and who had suffered verbal or physical violence in the past year had a higher risk of effort-reward imbalance. Furthermore, the nurses with a high monthly income, who believed that the number of nurses met the department's demand had a lower risk of effort-reward imbalance. CONCLUSIONS: Effort-reward imbalance was prevalent among emergency department nurses in China. Measures such as adjusting the night shift frequency, increasing the number of nurses, raising salaries and reducing workplace violence should be considered to reduce the level of effort-reward imbalance.

Quantifying the Susceptibility Variation of Normal-Appearing White Matter in Multiple Sclerosis by Quantitative Susceptibility Mapping.

OBJECTIVE: The purpose of this study is to evaluate the magnetic susceptibility of normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) using quantitative susceptibility mapping. MATERIALS AND METHODS: Ninety-four patients with relapse-remitting MS (RRMS) (37 with gadolinium-enhancing lesions and 57 with only gadolinium-nonenhancing lesions) and 55 healthy control subjects were included in this retrospective study. The susceptibility values of NAWM relative to CSF in patients with MS were compared with those of white matter (WM) in healthy control subjects and were correlated with the patient status of gadolinium-enhancing lesions, disease duration, and expanded disability status scale scores. RESULTS: All 37 patients with RRMS and gadolinium-enhancing lesions also had gadolinium-nonenhancing lesions. Susceptibility values of NAWM in patients with MS and only gadolinium-nonenhancing lesions (-18.29 ± 8.03 parts per billion [ppb]) were higher than those for WM in healthy control subjects (-25.81 ± 6.02 ppb; p < 0.001) and NAWM in patients with gadolinium-enhancing lesions (-25.64 ± 6.55 ppb; p < 0.001). Susceptibility values of NAWM in patients with MS with gadolinium-enhancing lesions were similar to those for WM in healthy control subjects (p = 0.91). This trend was dependent on neither NAWM region nor disease duration when the data were controlled for age. NAWM susceptibility was not correlated with either disease duration or expanded disability status scale (p > 0.05). CONCLUSION: In patients with RRMS and gadolinium-nonenhancing lesions, the susceptibility values of NAWM decrease when gadolinium-enhancing lesions appear, approaching values similar to those of WM in healthy control subjects, suggesting that NAWM may contribute to the iron accumulation observed in early active MS lesions.

Comparison of two different regimens of intravenous methylprednisolone for patients with moderate to severe and active Graves' ophthalmopathy: a prospective, randomized controlled trial.

The intravenous methylprednisolone (iv MP) strategy for Graves' ophthalmopathy (GO) and evaluation of its activity against the disease warrants further exploration. A prospective randomized controlled trial for 3 months was performed in a tertiary referral teaching hospital to compare the efficacy and safety of two different regimens of iv MP, and determine the value of clinical activity score (CAS) and T2 relaxation time (T2RTs) and areas of extraocular muscles (EOMs) by magnetic resonance imaging for diagnosis of active GO. Forty patients with moderate to severe GO and CAS ≥ 3 or 1 ≤ CAS < 3 with prolonged T2RTs on EOMs were randomly assigned to a monthly (MR: 1.5 g iv MP monthly for 3 months) or weekly (WR: 0.5 g iv MP weekly for 6 weeks, followed by 0.25 g weekly for 6 weeks) regimen. Overall response based on ophthalmic symptoms, T2RTs, areas of EOMs and adverse effects were recorded at each visit. The total rate of response was 71.9%. Rates of improved, unchanged, deteriorated were similar between the MR and WR groups (p>0.05). The maximum T2RTs and areas significantly decreased at the end of intervention in both groups (p<0.05). Results show that both MR and WR are effective and safe in treatment of GO. T2RTs combined with CAS can sensitively detect active GO and predict the response to iv MP.

Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas.

The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T2 relaxivity was 92.73 s-1mM-1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T2-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R2 value increased by 30% compared to baseline. However, T2-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.

Comparison of efficacy and safety of conventional transarterial chemoembolization and drug-eluting bead transarterial chemoembolization in unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective cohort study.

PURPOSE: The efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional TACE (c-TACE) in the treatment of patients with unresectable intrahepatic cholangiocarcinoma (ICC) remained controversial. Therefore, we aimed to compare the efficacy and safety between c-TACE and DEB-TACE among patients with ICC. METHOD: Between June 10, 2016 and November 19, 2022, consecutive patients with pathological diagnoses of ICC were divided into the DEB-TACE group and the c-TACE group based on the type of TACE treatment they received. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) between the two groups. Propensity score matching (PSM) was used to balance the characteristics between the c-TACE group and the DEB-TACE group. RESULTS: A total of 132 patients were included in this study, with 64 patients in the c-TACE group and 68 patients in the DEB-TACE group. The median OS for c-TACE and DEB-TACE was 5 and 12 months, respectively. The objective response rate (ORR) for c-TACE and DEB-TACE was 0 % and 66.2 %, respectively; the disease control rate (DCR) was 37.5 % and 91.2 %. There were no significant differences between c-TACE and DEB-TACE among adverse effects at 3 months after treatment (P > 0.05). The results remained consistent after PSM. The Cox regression demonstrated that the DEB-TACE was an independent protective factor for OS. CONCLUSIONS: Patients in the DEB-TACE group had longer OS and higher ORR and DCR than those in the c-TACE group, but no significant difference was observed between the two groups regarding adverse effects.

Diffusion tensor magnetic resonance imaging reveals visual pathway damage that correlates with clinical severity in glaucoma.

BACKGROUND: To investigate nerve fibre damage of the visual pathway in patients with primary open-angle glaucoma using tract-based spatial statistical analysis of diffusion tensor imaging and correlate these measures with the clinical severity of glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: Twenty-five individuals with primary open-angle glaucoma and 24 healthy controls were recruited. METHODS: All subjects underwent detailed ophthalmological examinations, including the cup-to-disc ratio, retinal nerve fibre layer thickness and visual fields test. Diffusion tensor imaging of the visual pathway was performed using a 3.0-T magnetic resonance scanner. MAIN OUTCOME MEASURES: Diffusivity changes of the nerve fibres in the visual pathway were calculated through tract-based spatial statistical analysis. The mean diffusivity and fractional anisotropy were assessed and compared with ophthalmological measurements. RESULTS: Compared with controls, bilateral optic tracts and optic radiations in primary open-angle glaucoma patients showed significantly decreased fractional anisotropy and increased mean diffusivity (P < 0.05). In the glaucoma group, the fractional anisotropy of the optic tracts and optic radiations varied consistently with the cup-to-disc ratio, retinal nerve fibre layer thickness and visual function analysis, respectively (P < 0.05). The mean diffusivity of the optic tracts correlated with these ophthalmological measurements (P < 0.05). However, no significant correlation was observed between the mean diffusivity of the optic radiations and the ophthalmological measurements (P > 0.05). CONCLUSIONS: The optic tracts and optic radiations of primary open-angle glaucoma patients demonstrated radiological evidence of neurodegeneration. This varied with damage to the optic disc and with the loss of visual function. Tract-based spatial statistical analysis of diffusion tensor imaging is an objective and effective tool for detecting the loss of cortical nerve fibres in primary open-angle glaucoma.

Correlation between lateral geniculate nucleus atrophy and damage to the optic disc in glaucoma.

PURPOSE: To investigate the relationship between morphological changes in the lateral geniculate nucleus (LGN), as measured by magnetic resonance imaging (MRI), and damage to the optic disc in primary open-angle glaucoma (POAG) patients. METHODS: A total of 23 patients with POAG and 23 age- and gender-matched non-glaucomatous subjects were enrolled. Every patient had structural damage to the optic disc. Cup-to-disc ratio (CDR) and retinal nerve fiber layer thickness (RNFLT) were measured, and 3.0-Tesla MRI examinations performed. Bilateral LGNs were identified and manually extracted, and their maximum heights and volumes compared with the clinical damage to the optic disc. RESULTS: In POAG patients, morphological changes in LGNs and RNFLT were consistently varied (P<0.05), while a negative correlation between LGN measurements and CDR was observed (P<0.05). LGN height was more significantly correlated with damage to the optic disc than was LGN volume. In contrast, no significant correlation was found between morphological changes in LGNs and age or optic disc parameters in the non-glaucomatous controls (P>0.05). CONCLUSION: LGN atrophy in POAG patients was altered in a manner consistent with damage to the optic disc. Morphological changes in LGNs as measured by MRI and especially LGN maximum height may be useful ways to detect optic nerve neuropathy in glaucoma.

The disulfidptosis-related signature predicts prognosis and immune features in glioma patients.

Glioma is the most common primary malignant tumor in the central nervous system. Disulfidptosis is a recently identified programmed cell death in tumor cells overexpressing SLC7A11 under glucose starvation. Clinical prognostic significance of disulfidptosis has been reported in several tumors, and in this study, we explored the correlation of disulfidptosis with clinical prognosis, immune cell infiltration, and immunotherapy response in glioma. A total of 1592 glioma patients were included in this study, including 691 glioma patients from The Cancer Genomic Atlas (TCGA), 300 patients with from the Chinese Glioma Genomic Atlas (CGGA) array, 325 patients from CGGA sequencing, and 276 patients from Gene Expression Omnibus (GEO) GSE16011. R software (V4.2.2) and several R packages were applied to develop the risk score model and correlation calculation and visualization. Three disulfidptosis-related genes, LRPPRC, RPN1, and GYS1, were screened out and applied to establish the risk score model. Low-risk patients exhibit favorable prognosis, and the disulfidptosis-related signature significantly correlated with clinicopathological properties, molecular subtypes, and immunosuppressive microenvironment of glioma patients. We developed a disulfidptosis-related risk model to predict the prognosis and immune features in glioma patients, and this risk model may be applied as an independent prognostic factor for glioma.

Conventional and drug-eluting beads transarterial chemoembolization in patients with unresectable intrahepatic cholangiocarcinoma: a systematic review and pooled analysis.

PURPOSE: Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have poor survival. Conventional transarterial chemoembolization (c-TACE) and drug-eluting beads transarterial chemoembolization (DEB-TACE) are two treatment options for ICC, and this systematic review describes the efficacy of each of these modalities for unresectable ICC to guide clinical practice. METHODS: A literature search was performed in PubMed, Web of Science, and Embase databases regarding transhepatic arterial chemoembolization for intrahepatic cholangiocarcinoma. The Newcastle-Ottawa quality assessment Scale (NOS) was used to assess the risk of bias. Tumor response, disease control, and 1-, 2-, 3-year overall survival rate were pooled for estimation. RESULTS: The number of initial search results was 1035, and 19 articles met the inclusion criteria for this study after the screening. A total of 23 study cohorts and 1091 patients were provided. The pooled objective response rate (ORR) for c-TACE and DEB-TACE treating ICC was 29.4% (95% CI 11.6-50.8%) and 51.2% (95% CI 30.6-71.7%), respectively; disease control rate (DCR) was 72.8% (95% CI 55.6-87.3%) and 88.7% (95% CI 78.8-96.2%), respectively. The pooled survival rate at 1 year, 2 year, and 3 year was 49.7% (95% CI 39.1-60.3%), 24.0% (95% CI 12.6-37.3%), and 23.5% (95% CI 11.1-38.7%) for c-TACE; 58.6% (95% CI 44.2-72.3%), 26.7% (95% CI 18.1-36.3%), and 16.2% (95% CI 6.0-29.4%) for DEB-TACE. CONCLUSION: The descriptive analysis suggested that DEB-TACE treatment for ICC may have better tumor response and disease control rates than c-TACE treatment, but the impact on overall survival was not demonstrated significantly by DEB-TACE treatment.

Application of a Radiomics Machine Learning Model for Differentiating Aldosterone-Producing Adenoma from Non-Functioning Adrenal Adenoma.

To evaluate the secretory function of adrenal incidentaloma, this study explored the usefulness of a contrast-enhanced computed tomography (CECT)-based radiomics model for distinguishing aldosterone-producing adenoma (APA) from non-functioning adrenal adenoma (NAA). Overall, 68 APA and 60 NAA patients were randomly assigned (8:2 ratio) to either a training or a test cohort. In the training cohort, univariate and least absolute shrinkage and selection operator regression analyses were conducted to select the significant features. A logistic regression machine learning (ML) model was then constructed based on the radiomics score and clinical features. Model effectiveness was evaluated according to the receiver operating characteristic, accuracy, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis. In the test cohort, the area under the curve (AUC) of the Radscore model was 0.869 [95% confidence interval (CI), 0.734-1.000], and the accuracy, sensitivity, specificity, and F1 score were 0.731, 1.000, 0.583, and 0.900, respectively. The Clinic-Radscore model had an AUC of 0.994 [95% CI, 0.978-1.000], and the accuracy, sensitivity, specificity, and F1 score values were 0.962, 0.929, 1.000, and 0.931, respectively. In conclusion, the CECT-based radiomics and clinical radiomics ML model exhibited good diagnostic efficacy in differentiating APAs from NAAs; this non-invasive, cost-effective, and efficient method is important for the management of adrenal incidentaloma.

Efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization using CalliSpheres in treating huge hepatocellular carcinoma patients.

BACKGROUND: The treatment of huge hepatocellular carcinoma (HCC) is still challengeable due to its deteriorative heterogeneity, for which conventional transarterial chemoembolization (TACE) is proposed as an efficient therapy; however, drug-eluting beads TACE (DEB-TACE) is rarely reported in these patients. Thus, the current study aimed to explore the efficacy, prognostic factors, and safety of DEB-TACE using CalliSpheres in huge HCC patients. METHODS: Ninety-nine huge HCC patients treated by DEB-TACE using CalliSpheres were retrospectively reviewed. Treatment response, change of tumor markers, liver function indexes, progression-free survival (PFS), and adverse events were retrieved. RESULTS: Objective response rate (ORR) was 66.1%, 48.6%, and 23.8%, then disease control rate (DCR) was 85.5%, 67.6%, and 33.3% at month (M) 1, M3, and M6, respectively; furthermore, carcinoembryonic antigen (CEA) (p = 0.037), alpha fetoprotein (AFP) (p < 0.001), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) (p < 0.001) were all declined at 1 month after DEB-TACE. The median PFS was 8.3 (95% confidence interval: 6.0-10.6) months with 1-year and 2-year PFS rates of 38.5% and 15.5%, accordingly. Moreover, elevated China liver cancer (CNLC) stage (p = 0.036, hazard ratio (HR): 1.937) and abnormal cancer antigen 199 (p = 0.019, HR: 2.465) were correlated with unfavorable PFS. Besides, liver function indexes were not deteriorated after DEB-TACE. Lastly, main adverse events included pain (20.2%), fever (17.2%), nausea (14.1%), and vomit (9.1%), which were mild and manageable. CONCLUSION: DEB-TACE using CalliSpheres presents satisfying efficacy and tolerable safety in huge HCC patients, suggesting that it might be a good treatment option for these patients.

Single-cell RNA sequencing of CSF reveals neuroprotective RAC1+ NK cells in Parkinson's disease.

Brain infiltration of the natural killer (NK) cells has been observed in several neurodegenerative disorders, including Parkinson's disease (PD). In a mouse model of α-synucleinopathy, it has been shown that NK cells help in clearing α-synuclein (α-syn) aggregates. This study aimed to investigate the molecular mechanisms underlying the brain infiltration of NK cells in PD. Immunofluorescence assay was performed using the anti-NKp46 antibody to detect NK cells in the brain of PD model mice. Next, we analyzed the publicly available single-cell RNA sequencing (scRNA-seq) data (GSE141578) of the cerebrospinal fluid (CSF) from patients with PD to characterize the CSF immune landscape in PD. Results showed that NK cells infiltrate the substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice and colocalize with dopaminergic neurons and α-syn. Moreover, the ratio of NK cells was found to be increased in the CSF of PD patients. Analysis of the scRNA-seq data revealed that Rac family small GTPase 1 (RAC1) was the most significantly upregulated gene in NK cells from PD patients. Furthermore, genes involved in regulating SN development were enriched in RAC1+ NK cells and these cells showed increased brain infiltration in MPTP-induced PD mice. In conclusion, NK cells actively home to the SN of PD model mice and RAC1 might be involved in regulating this process. Moreover, RAC1+ NK cells play a neuroprotective role in PD.

Precise Fabrication of Porous Microspheres by Iso-Density Emulsion Combined with Microfluidics.

Polymer porous microspheres with large specific surface areas and good fluidity have promising important applications in the biomedical field. However, controllable fabrication of porous microspheres with precise size, morphology, and pore structure is still a challenge, and phase separation caused by the instability of the emulsion is the main factor affecting the precise preparation of porous microspheres. Herein, a method combining the iso-density emulsion (IDE) template and microfluidics was proposed to realize the controllable preparation of polymer porous microspheres. The IDE exhibited excellent stability with minimal phase separation within 4 h, thus showing potential advantages in the large-scale preparation of porous microspheres. With the IDE template combined microfluidics technique and the use of a customized amphoteric copolymer, PEG-b-polycaprolactone, polycaprolactone (PCL) porous microspheres with porosity higher than 90% were successfully prepared. Afterwards, the main factors, including polymer concentration, water-oil ratio and homogenization time were investigated to regulate the pore structure of microspheres, and microspheres with different pore sizes (1-30 µm) were obtained. PCL porous microspheres exhibited comparable cell viability relative to the control group and good potential as cell microcarriers after surface modification with polydopamine. The modified PCL porous microspheres implanted subcutaneously in rats underwent rapid in vivo degradation and tissue ingrowth. Overall, this study demonstrated an efficient strategy for the precise preparation of porous microspheres and investigated the potential of the as-prepared PCL porous microspheres as cell microcarriers and micro-scaffolds.

Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy.

The tumor microenvironment with overexpressed hydrogen peroxide (H2O2) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS-based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with H2O2 to produce •OH and release Cu2+. Then, the Cu2+ further depletes GSH to generate Cu+ for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize CDT. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.