ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via mTORC1-TFEB-BLOC1S3 axis.

Zinc oxide nanoparticles (ZNPs) are widely used in sunscreens and nanomedicines, and it was recently confirmed that ZNPs can penetrate stratum corneum into deep epidermis. Therefore, it is necessary to determine the impact of ZNPs on epidermis. In this study, ZNPs were applied to mouse skin at a relatively low concentration for one week. As a result, desmosomes in epidermal tissues were depolymerized, epidermal mechanical strain resistance was reduced, and the levels of desmosomal cadherins were decreased in cell membrane lysates and increased in cytoplasmic lysates. This finding suggested that ZNPs promote desmosomal cadherin endocytosis, which causes desmosome depolymerization. In further studies, ZNPs were proved to decrease mammalian target of rapamycin complex 1 (mTORC1) activity, activate transcription factor EB (TFEB), upregulate biogenesis of lysosome-related organelle complex 1 subunit 3 (BLOC1S3) and consequently promote desmosomal cadherin endocytosis. In addition, the key role of mTORC1 in ZNP-induced decrease in mechanical strain resistance was determined both in vitro and in vivo. It can be concluded that ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via the mTORC1-TFEB-BLOC1S3 axis. This study helps elucidate the biological effects of ZNPs and suggests that ZNPs increase the risk of epidermal fragmentation.

Numerical simulation study on the evolution law of mechanical properties of different metamorphic coals after heat treatment.

In order to study the effect of temperature on the structure and mechanical properties of coal with different metamorphic degree. Three coal samples with varying degrees of metamorphism were chosen for analysis. The discrete element software PFC2D is used to simulate the heat treatment and compression of coal. The findings indicate that during the heating process, low-order coal exhibits noticeable thermal cracks at an early stage, while thermal crack development in middle-order coal is concentrated in the later stages. In contrast, high-order coal demonstrates a more stable macroscopic structure. The strength and stiffness of low rank coal show the lowest value and decrease significantly within 135 °C. However, the strength and stiffness of medium rank coal decrease significantly after 135 °C. The changes of mechanical properties and damage modes of coal caused by thermal damage are often ignored, which may lead to the deviation of design and research results from the actual situation. Therefore, this study is of great significance to the prevention and control of coal mine disasters.

Experimental Study on the Inhibition Effect of the Inhibitor on Coal Spontaneous Combustion Under Critical Temperature.

At present, related research on inhibitors has been gradually improved, but there is still a lack of research on the inhibition characteristics at specific release temperatures and the mechanism of inhibiting coal spontaneous combustion. Based on this, In this study, the inhibition characteristics of adding inhibitor to coal under critical temperature (R70) are studied in depth. In the experiment, lignite was selected as the research object, and four different types of inhibitors, MgCl2, triphenyl phosphite (TPPI), Phytic acid (PA), and melatonin, were applied to coal samples at room temperature and 70 °C, respectively. The temperature-programmed-gas chromatography test and Fourier infrared spectroscopy experiment were carried out, and the oxidation kinetic parameters were calculated to study the oxidation characteristics and micromechanism of the coal samples in the process of spontaneous combustion. The experimental results show that the amount of CO gas release and oxygen consumption rate are lower, and the inhibition rate and apparent activation energy are higher when the inhibitor is added under R70 than at room temperature. Under R70, the content of oxygen-containing functional group -COOH with higher activity of inhibitor is reduced, the generation of active sites is inhibited, the concentration of active center is reduced, the path of mutual transformation between active sites and oxygen-containing functional groups is blocked, and the active groups are promoted to form a relatively stable inert oxygen-containing ether bond, which reduces the spontaneous combustion tendency of coal.

An ultrasound-triggered injectable sodium alginate scaffold loaded with electrospun microspheres for on-demand drug delivery to accelerate bone defect regeneration.

Biological processes, such as bone defects healing are precisely controlled in both time and space. This spatiotemporal characteristic inspires novel therapeutic strategies. The sustained-release systems including hydrogels are commonly utilized in the treatment of bone defect; however, traditional hydrogels often release drugs at a consistent rate, lacking temporal precision. In this study, a hybrid hydrogel has been developed by using sodium alginate, sucrose acetate isobutyrate, and electrospray microspheres as the base materials, and designed with ultrasound response, and on-demand release properties. Sucrose acetate isobutyrate was added to the hybrid hydrogel to prevent burst release. The network structure of the hybrid hydrogel is formed by the interconnection of Ca2+ with the carboxyl groups of sodium alginate. Notably, when the hybrid hydrogel is exposed to ultrasound, the ionic bond can be broken to promote drug release; when ultrasound is turned off, the release returned to a low-release state. This hybrid hydrogel reveals not only injectability, degradability, and good mechanical properties but also shows multiple responses to ultrasound. And it has good biocompatibility and promotes osteogenesis efficiency in vivo. Thus, this hybrid hydrogel provides a promising therapeutic strategy for the treatment of bone defects.

Experimental study on the effect of room temperature pre-oxidized time on spontaneous combustion characteristics of coal.

The presence of different types of coal at room temperature can lead to self-heating of coal, potentially resulting in spontaneous combustion. To investigate the effect of ambient temperature pre-oxidation (BL) time on the self-combustion characteristics of different coal types, synchronous thermal analysis (STA) and Fourier-transform infrared spectroscopy (FTIR) experiments were conducted. The results of the synchronous thermal analysis experiments indicate that ambient temperature pre-oxidation for 3 months (BL3), BL6, and BL9 coals exhibit faster oxidation reactions compared to the original coal, while BL12 coal shows slower oxidation than the original coal. Among these, BL9 coal demonstrates the most significant changes in oxidation reaction characteristics, with the fastest oxidation reaction time being 35.36 min, which is 1.38 min faster than the original coal. To support this observation, a comparison was made between the relative content of active functional groups in the original coal and BL coal. The study revealed that the BL process affects the relative content of hydroxyl groups, aromatic hydrocarbons, aliphatic hydrocarbons, and oxygen-containing functional groups, thereby influencing the coal-oxygen reaction process. This suggests that pre-oxidized coal, compared to the original coal, has a larger pore structure, which plays a dominant role in promoting coal self-combustion in the first 9 months of the BL process. As BL time continues to increase, the continuous reaction of active functional groups at room temperature leads to excessive consumption, resulting in a more significant role in inhibiting coal self-combustion. The research results provide valuable insights for predicting the spontaneous combustion risk of oxidized coal.

[Research progress on chemical constituents and pharmacological activities of halogenated sesquiterpenes from natural sources].

Halogenated sesquiterpenes are important derivatives of sesquiterpenes, referring to chemical components of sesquiterpenes that contain halogens such as chlorine, bromine, and iodine. Halogenated sesquiterpenes have attracted attention from researchers in China and abroad because of their diverse structures, unique halogen elements, and extensive pharmacological activities. Studies have shown that halogenated sesquiterpenes exhibit significant antimicrobial, anti-inflammatory, anticancer, insecticidal, hypoglycemic, and enzyme inhibitory activities. In order to better explore the potential pharmaceutical value of halogenated sesquiterpenes, this paper reviewed the structural characteristics and pharmacological activities of halogenated sesquiterpenes in the past two decades, aiming to provide references for further research and development of this class of compounds.

Phytochemistry and pharmacology of natural prenylated flavonoids.

Prenylated flavonoids are a special kind of flavonoid derivative possessing one or more prenyl groups in the parent nucleus of the flavonoid. The presence of the prenyl side chain enriched the structural diversity of flavonoids and increased their bioactivity and bioavailability. Prenylated flavonoids show a wide range of biological activities, such as anti-cancer, anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, cardioprotective effects, and anti-osteoclastogenic activities. In recent years, many compounds with significant activity have been discovered with the continuous excavation of the medicinal value of prenylated flavonoids, and have attracted the extensive attention of pharmacologists. This review summarizes recent progress on research into natural active prenylated flavonoids to promote new discoveries of their medicinal value.

The Impact of Oversizing in Thoracic Endovascular Aortic Repair on Long-Term Outcomes in Uncomplicated Type B Aortic Dissection: A Single-Center Retrospective Study.

PURPOSE: The purpose of this study was to assess the impact of oversizing in thoracic endovascular aortic repair (TEVAR) on early and long-term survival and major adverse events in patients with uncomplicated type B aortic dissection (TBAD). METHODS: Between January 2010 and December 2018, 226 patients who were diagnosed with uncomplicated TBAD and received TEVAR were analyzed retrospectively. The patients were divided into ≤5% oversizing (n=153) and >5% oversizing (n=73) groups. Primary end points were all-cause and aortic-related mortalities. Secondary end points were procedure-related complications, including retrograde type A aortic dissection (RTAD), endoleak, distal stent-induced new entry (SINE), and late reintervention. All-cause and aortic-related mortalities were assessed using the Kaplan-Meier survival method, while procedure-related complications were evaluated using a competing risk model with all-cause death as a competing risk. RESULTS: Mean oversizing was 2.1%±1.5% in the ≤5% oversizing group and 9.6%±4.1% in the >5% oversizing group. Differences in the 30-day mortality and adverse events between the 2 groups were statistically insignificant. The freedom from all-cause mortality was comparable between the ≤5% oversizing group and the >5% oversizing group (≤5%: 93.3% at 5 years, >5%: 92.3% at 5 years, p=0.957). No significant difference was observed between both groups in the freedom from aortic-related mortality (≤5%: 95.0% at 5 years, >5%: 96.7% at 5 years, p=0.928). However, the competing risk analyses revealed that the cumulative incidence of RTAD was statistically significantly greater in the >5% oversizing group than in the ≤5% oversizing group (≤5%: 1(0.7%) at 5 years, >5%: 6(6.9%) at 5 years, p=0.007). All RTADs occurred within a year of TEVAR. The differences in the cumulative incidences of type I endoleak, distal SINE, and late reintervention were not significant between the 2 groups. CONCLUSION: The differences in the 5-year all-cause mortality and aortic-related mortality between patients with uncomplicated TBAD who received TEVAR with ≤5% oversizing and those who got TEVAR with >5% oversizing were insignificant. However, oversizing >5% was considerably associated with an increased risk of RTAD within a year of TEVAR, suggesting that oversizing ≤5% may be the appropriate size for TEVAR in patients with uncomplicated TBAD. CLINICAL IMPACT: For patients with uncomplicated TBAD, choosing oversizing ≤5% in endovascular treatment is beneficial to reduce the risk of postoperative retrograde type A aortic dissection. This finding provides a basis for stent size selection in endovascular repair. In addition, one year after TEVAR is the main time period for postoperative retrograde type A aortic dissection, and attention should be paid to the management and follow-up of this period.

Endovascular treatment of aorto-iliac occlusive disease with TASC II C and D lesions: 10 year's experience of clinical technique.

OBJECTIVES: The purpose of this study was to evaluate the therapeutic efficacy and safety of endovascular treatment aorto-iliac occlusive disease (AIOD) with TransAtlantic Inter-Society Consensus II (TASC II) C and D lesions. In addition, 10 years of experience with interventional procedures and treatment options in our center were also worthy of further discussion. METHODS: Between January 2011 and December 2020, a total of 26 consecutive AIOD patients with TASC-II C and D lesions treated endovascular approach were enrolled in this study. Patients' demographic and clinical data were collected, and the safety and efficacy of endovascular therapy were evaluated. In addition, operation procedures were also described. RESULTS: The mean age of patients was 62.2 ± 7 years (49-57 years), and the mean body mass index of patients was 24.2 ± 2.6 kg/m2. Fifteen patients (57.7%) were Rutherford 4, 5 each (19.2%) were Rutherford 3 and 5, and 1 (3.8%) was Rutherford 2. No other serious complications occurred except death in 3 patients. Most of the patients (73.1%) had a history of smoking, and hypertension and hyperlipidemia were common comorbidities. Endovascular therapy was successfully performed in 25 patients, and the technical success rate was 96.2%. The patient's ankle-brachial index improved significantly postoperatively compared with preoperatively (preoperative 0.33 ± 0.14 vs 1.0 ± 0.09, P < 0.001). The primary patency rates were 100%, 95.7%, and 91.3% at 1, 3, and 5 years, while the secondary patency rates were 100%. No treatment-related deaths or serious complications occurred. CONCLUSIONS: Endovascular treatment of AIOD patients with TASC-II C and D lesions might be safe and have a high rate of middle-term and long-term primary patency.

Risk factors for distal stent graft-induced new entry after endovascular repair in uncomplicated type B aortic dissection.

OBJECTIVE: We investigated the risk factors for distal stent graft-induced new entry (dSINE) after thoracic endovascular aortic repair for patients with uncomplicated type B aortic dissection (TBAD) and reported the outcomes of using a tapered stent graft and dSINE reintervention. METHODS: A total of 226 patients with uncomplicated TBAD who had undergone thoracic endovascular aortic repair between January 2010 and December 2018 were analyzed retrospectively. The global features of the thoracic aorta and the local features of the proximal and distal landing zones were evaluated and compared between the dSINE and non-dSINE groups. A multivariate Cox model was used to identify the independent risk factors for dSINE. The cumulative incidence of reintervention was estimated using competing risk models. RESULTS: After a median follow-up of 4.6 years, 16 patients (7.1%) had developed dSINE. Multivariable Cox regression analysis demonstrated that a type III aortic arch, decreased angle, increased distal oversizing, and increased distal mismatch ratio were significant risk factors for dSINE. Of the patients with tapered stent grafts, five with a ≤4-mm taper had developed dSINE. However, no dSINE was seen in the >4-mm taper group (P = .024). Reintervention was performed for 7 of the 16 patients with dSINE (43.8%). The mean time from the initial detection of dSINE to reintervention was 6.43 ± 4.62 months. The competing risk analyses showed that the cumulative incidence of reintervention in the dSINE group at 1, 3, and 5 years was 25.0%, 37.5%, and 43.5%, respectively. CONCLUSIONS: A type III aortic arch, excessive distal oversizing and mismatch ratio, and severe angulation were associated with dSINE in patients with uncomplicated TBAD. The use of a tapered stent graft with a >4-mm taper could help prevent dSINE in patients with a high taper ratio. Aggressive reintervention was associated with favorable long-term outcomes for patients with progressive dSINE.

Efficacy and evaluation of therapeutic exercises on adults with Parkinson's disease: a systematic review and network meta-analysis.

BACKGROUND: Exercises are an effective treatment in Parkinson's disease (PD), but there is still controversy over which types should be used. We aimed to compare and rank the types of exercise that improve PD symptoms by quantifying information from randomised controlled trials. METHODS: We performed a systematic review and network meta-analysis and searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and China National Knowledge Infrastructure (CNKI) from their inception date to June 30, 2022. We included randomized controlled trials of 24 types of exercise for the interventional treatment of adults (≥ 50 years old) with PD. Effect size measures were standardized mean differences (SMDs) with 95% credible intervals (CrIs). The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). RESULTS: We identified 10 474 citations and included 250 studies involving 13 011 participants. Results of NMA showed that power training (PT) had the best benefits for motor symptoms compared with the control group (CON), with SMDs (95% CrI) (-1.46, [-2.18 to -0.74]). Body weight support treadmill training (BWS_TT) showed the best improvement in balance (1.55, [0.72 to 2.37]), gait velocity (1.15 [0.57 to 1.31]) and walking distance (1.96, [1.18 to 2.73]), and robotic assisted gait training (RA_GT) had the most benefits for freezing of gait (-1.09, [-1.80 to -0.38]). For non-motor symptoms, Dance showed the best benefits for depression (-1.71, [-2.79 to -0.73]). Only Yoga significantly reduced anxiety symptom compared with CON (-0.53, [0.96 to -0.11]). Only resistance training (RT) significantly enhanced sleep quality and cognition (-1.42, [-2.60 to -0.23]; 0.51, [0.09 to 0.94]). For muscle strength, PT showed the best advance (1.04, [0.64 to 1.44]). For concern of falling, five types of exercise were more effective than CON. CONCLUSIONS: There is low quality evidence that PT, Yoga, BWS_TT, Dance, and RT are the most effective treatments, pending outcome of interest, for adults with PD. TRIAL REGISTRATION: PROSPERO (CRD42021220052).

C-Arm Cone-Beam CT Virtual Navigation versus Conventional CT Guidance in the Transthoracic Lung Biopsy: A Case-Control Study.

C-arm cone-beam computed tomography (CBCT) virtual navigation-guided lung biopsy has been developed in the last decade as an alternative to conventional CT-guided lung biopsy. This study aims to compare the biopsy accuracy and safety between these two techniques and explores the risk factors of biopsy-related complications. A total of 217 consecutive patients undergoing conventional CT- or C-arm CBCT virtual navigation-guided lung biopsy from 1 June 2018 to 31 December 2019 in this single-center were retrospectively reviewed. Multiple factors (e.g., prior emphysema, lesion size, etc.) were compared between two biopsy techniques. The risk factors of complications were explored by using logistic regression. The patients' median age and male-to-female ratio were 63 years and 2.1:1, respectively. Eighty-two (82) patients (37.8%) underwent conventional CT-guided biopsies, and the other 135 patients (62.2%) C-arm CBCT virtual navigation-guided biopsies. Compared with patients undergoing C-arm CBCT virtual navigation-guided lung biopsies, patients undergoing conventional CT-guided lung biopsies showed higher needle repositioning rate, longer operation time, and higher effective dose of X-ray (52.4% vs. 6.7%, 25 min vs. 15 min, and 13.4 mSv vs. 7.6 mSv, respectively; p < 0.001, each). In total, the accurate biopsy was achieved in 215 of 217 patients (99.1%), without a significant difference between the two biopsy techniques (p = 1.000). The overall complication rates, including pneumothorax and pulmonary hemorrhage/hemoptysis, are 26.3% (57/217), with most minor complications (56/57, 98.2%). The needle repositioning was the only independent risk factor of complications with an odds ratio of 6.169 (p < 0.001). In conclusion, the C-arm CBCT virtual navigation is better in percutaneous lung biopsy than conventional CT guidance, facilitating needle positioning and reducing radiation exposure. Needle repositioning should be avoided because it brings about more biopsy-related complications.

Timing of endovascular repair impacts long-term outcomes of uncomplicated acute type B aortic dissection.

OBJECTIVE: To compare the 5-year outcomes of acute versus subacute thoracic endovascular aortic repair (TEVAR) in patients with uncomplicated acute type B aortic dissection (ATBAD). METHODS: Between March 2008 and September 2018, 238 consecutive patients with uncomplicated ATBAD underwent TEVAR in the acute or subacute phase and were analyzed retrospectively. The primary end points were all-cause death and aortic-related death. The secondary end point was a composite of the outcomes of death from any cause, rupture, new dissection, retrograde type A aortic dissection, endoleak, and late reintervention. Inverse probability treatment weighting was used to balance baseline characteristics. Weight-adjusted Kaplan-Meier estimate with landmark analysis and weighted Cox model were performed to assess time-to-event outcomes. RESULTS: In the inverse probability treatment weighting-adjusted population, the 30-day mortality was 1.5% in the acute TEVAR group and 0% in the subacute TEVAR group (P = .24). The incidence of 30-day adverse events occurred in 16.8% and 6.9% patients in the acute TEVAR and subacute TEVAR groups, respectively (P = .13). At 5 years, there was no statistically significant difference in all-cause death (hazard ratio [HR], 1.50; 95% confidence interval [CI], 0.59-3.81; P = .39) and aortic-related death (HR, 1.11; 95% CI, 0.34-3.60; P = .86) between the two groups. The composite outcomes occurred in 30 patients (23.0%) in the acute TEVAR group and 18 patients (22.3%) in the subacute TEVAR group, respectively (HR, 0.67; 95% CI, 0.36-1.25; P = .20). However, a landmark analysis of the composite outcomes indicated that there was a significant interaction between treatment effect and time (Pinteraction = .01), with a significantly higher incidence of the composite outcomes in the acute TEVAR group compared with the subacute TEVAR group within 1 year (HR, 0.25; 95% CI, 0.08-0.79; P = .02), and a comparable rate between 1 and 5 years (HR, 1.25; 95% CI, 0.56-2.76; P = .59). CONCLUSIONS: At the 5-year follow-up, no significant differences exist in the all-cause death and aortic-related death between acute and subacute TEVAR. However, acute TEVAR is associated with an increased rate of severe complications within 1 year, which suggests that performing TEVAR in the subacute phase of ATBAD may be the preferable option.

Protective Effect of Raf-1 Kinase Inhibitory Protein on Diabetic Retinal Neurodegeneration through P38-MAPK Pathway.

PURPOSE: This study aimed to investigate the effect of Raf-1 kinase inhibitory protein (RKIP) on diabetic retinal neurodegeneration in streptozotocin-treated rat model and high glucose-treated rat Müller cells. METHODS: Control and streptozotocin-treated rats were intravitreally injected with saline, RKIP gene overexpression lentivirus (oeRKIP) or negative control lentivirus (RKIP-vector). Normal or high glucose-treated Müller cells were transfected with saline, RKIP gene overexpression lentivirus or negative control lentivirus. Western blotting and immunofluorescence assay were utilized to evaluate the function of RKIP on the expression of RKIP, p38 mitogen-activated protein kinase (p38-MAPK), glutamate/aspartate transporter (GLAST), glutamine synthetase (GS), glial fibrillar acidic protein (GFAP) and cysteine-aspartic acid protease-3 (caspase-3). A glutamate assay kit was adopted to detect glutamate level in retina samples. Apoptosis of Müller cells was determined by Annexin-V/PI staining and flow cytometry. RESULTS: High glucose-treated Müller cells exhibited promoted apoptosis, while RKIP overexpression in high glucose-treated Müller cells down-regulated the enhanced apoptosis. Compared with rats injected with saline, streptozotocin-treated hyperglycemic rats displayed enhancement in the immunoreactivities of p38-MAPK and GFAP as well as in the protein expression of p38-MAPK and caspase-3. Strikingly, intravitreal injection of RKIP gene overexpression lentivirus in the hyperglycemic rats reversed the augmented immunoreactivities and protein expression mentioned above. Meanwhile, RKIP overexpression in the hyperglycemic rats improved the immunoreactivities and protein expression of RKIP, GS and GLAST. Besides, RKIP down-regulated the increased level of retinal glutamate in the hyperglycemic rats. CONCLUSIONS: Intravitreal injection of RKIP gene overexpression lentivirus functioned in preventing diabetic retinal neurodegeneration in a rat model of diabetes presumably by inhibiting p38-MAPK pathway.

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-ß Associated Neurodegenerative Pathways and Glial Signatures in a Mouse Model of Alzheimer's Disease: A Targeted Transcriptome Analysis.

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer's disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, it remains unclear how Arg1 deficiency in these cells impacts the whole brain to promote amyloidosis. Herein, we aim to determine how Arg1 deficiency driven by LysM restriction during amyloidosis affects fundamental neurodegenerative pathways at the transcriptome level. By applying several bioinformatic tools and analyses, we found that amyloid-ß (Aß) stimulated transcriptomic signatures in autophagy-related pathways and myeloid cells' inflammatory response. At the same time, myeloid Arg1 deficiency during amyloidosis promoted gene signatures of lipid metabolism, myelination, and migration of myeloid cells. Focusing on Aß associated glial transcriptomic signatures, we found myeloid Arg1 deficiency up-regulated glial gene transcripts that positively correlated with Aß plaque burden. We also observed that Aß preferentially activated disease-associated microglial signatures to increase phagocytic response, whereas myeloid Arg1 deficiency selectively promoted homeostatic microglial signature that is non-phagocytic. These transcriptomic findings suggest a critical role for proper Arg1 function during normal and pathological challenges associated with amyloidosis. Furthermore, understanding pathways that govern Arg1 metabolism may provide new therapeutic opportunities to rebalance immune function and improve microglia/macrophage fitness.

Combined Ultrasound and CT-Guided Iodine-125 Seeds Implantation for Treatment of Residual Hepatocellular Carcinoma Located at Complex Sites After Transcatheter Arterial Chemoembolization.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of iodine-125 (125I) seeds implantation under ultrasound and computed tomography (CT) guidance in the treatment of residual hepatocellular carcinoma (HCC) located at complex sites after transcatheter arterial chemoembolization (TACE). METHODS: This retrospective study analyzed the consecutive medical records of 31 HCC patients with residual tumors located at complex sites (such as large blood vessels, gallbladder, diaphragm dome, etc.) after TACE from May 2014 to December 2018, all of whom received 125I seeds implantation therapy. Overall survival (OS), progression-free survival (PFS), recurrence, and complications were documented. RESULTS: A total of 607 seeds were implanted in 31 patients, with an average of 19.6±10.4 (range, 8-48) seeds per patient. Median OS and PFS were 33 months (95% CI: 27.1 months, 38.9 months) and 15 months (95% CI: 9.6 months, 20.4 months), respectively. Although univariate analysis showed that albumin, prothrombin time, alpha-fetoprotein level, Child-Pugh score, and lipiodol deposition in tumor were associated with OS, multivariate analysis showed that none of them was an independent prognostic factor for OS. Multivariate analysis showed that prothrombin time was an independent prognostic factor for PFS. No operation-related deaths in this study. Although pneumothorax was present in two patients and subcutaneous abscess in one patient, symptoms improved in all three patients with appropriate treatment. Common minor complications included fever, abdominal pain and leukopenia and no grade≥3 adverse events were observed. CONCLUSIONS: 125I seeds implantation under the combined guidance of ultrasound and CT is safe and effective for patients with residual HCC located at complex sites after TACE. This is a promising treatment approach and deserves further discussion.

Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology.

Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell's response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer's disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to the greatest extent. We showed that sustained AZIN2 overexpression elicited a maladaptive PSR in mice with underlying tauopathy (MAPT P301S; PS19). AZIN2 also increased acetylpolyamines, augmented tau deposition, and promoted cognitive and affective behavioral impairments. Higher-order polyamines displaced microtubule-associated tau to facilitate polymerization but also decreased tau seeding and oligomerization. Conversely, acetylpolyamines promoted tau seeding and oligomers. These data suggest that tauopathies launch an altered enzymatic signature that endorses a feed-forward cycle of disease progression. Taken together, the tau-induced PSR affects behavior and disease continuance, but may also position the polyamine pathway as a potential entry point for plausible targets and treatments of tauopathy, including AD.

Tantalum Particles Induced Cytotoxic and Inflammatory Effects in Human Monocytes.

The aim of this study is to evaluate the biological safety of tantalum (Ta) particles and to further explore the effects of Ta particles on human monocyte toxicity and inflammatory cytokine expression. Human monocyte leukemia (THP-1) cells were cultured with Ta and hydroxyapatite (HA) particles. Cell counting kit-8 method was used to evaluate the cytotoxicity of Ta and HA particles. The apoptosis effects were evaluated by flow cytometry, and the protein expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated by ELISA. The protein levels of inflammation-related signaling pathways including nuclear factor-kappa B (NF-κB) and extracellular regulated kinase (ERK) were detected by western blotting. The cytotoxicity test showed that the toxicity level of Ta in vitro was grade l, which is within the clinically acceptable range. Compared with the HA control, Ta had no significant effect on THP-1 cell apoptosis, IL-6, and TNF-α release. The phosphorylated levels of NF-κB and ERK at 3 h in the Ta group were lower than those in the HA and control groups (P < 0.001 both). These results reveal Ta particles behave good biosafety properties and provide some new insights for the future clinical use of Ta.

ZnO NPs delay the recovery of psoriasis-like skin lesions through promoting nuclear translocation of p-NFκB p65 and cysteine deficiency in keratinocytes.

BACKGROUND: This study aimed to evaluate the safety of applying zinc oxide nanoparticles (ZnO NPs) to pathological skin. The majority of previous studies confirmed the safety of applying ZnO NPs to normal skin. However, we know very little about the risks of using sunscreen, cosmetics and topical drugs containing ZnO NPs for individuals with skin diseases. RESULTS: ZnO NPs passed through gaps between keratinocytes and entered stratum basale of epidermis and dermis in imiquimod-induced psoriasis-like skin lesions. Application of a ZnO NP-containing suspension for 3 connective days delayed the healing of the epidermal barrier; increased the expression levels of inflammatory cytokines; promoted keratinocyte apoptosis and disturbed redox homeostasis. In TNF-α-stimulated HaCaT cells, QNZ and JSH-23 (NFκB inhibitors) blocked ZnO NP-induced inflammation. JSH-23 and NAC (a precursor of cysteine) inhibited ZnO NP-induced nuclear translocation of p-NFκB p65, cysteine deficiency and apoptosis. Additionally, ZnO NPs decreased CD98 level in main pathway and failed to activate transsulfuration pathway in cysteine biosynthesis. CONCLUSIONS: ZnO NPs can enter psoriasis-like skin lesions and promote inflammation and keratinocyte apoptosis through nuclear translocation of p-NFκB p65 and cysteine deficiency. This work reminds the public that ZnO NPs have harmful effects on the recovery of inflammatory skin diseases.

Comparison of mid-term outcomes of endovascular repair and medical management in patients with acute uncomplicated type B aortic dissection.

OBJECTIVES: To further assess the early and mid-term outcomes of thoracic endovascular aortic repair (TEVAR) in patients with acute uncomplicated type B aortic dissection (TBAD) compared with those receiving best medical treatment (BMT). METHODS: Between February 2008 and March 2018, 357 consecutive patients with acute uncomplicated TBAD were retrospectively analyzed. Among them, 191 patients underwent TEVAR, and 166 received BMT. After propensity score matching, we obtained 145 matched pairs for analysis. RESULTS: In the matched population, the 30-day mortality between the TEVAR group and the BMT group showed no statistically significant difference, whereas the early adverse events rates in the TEVAR group were significantly greater than that of the BMT group (P = .003). Freedom from all-cause mortality in the TEVAR group was significantly greater than that of the BMT group (TEVAR: 91.9% at 5 years, BMT: 82.2% at 5 years, P = .028). Freedom from aortic-related mortality in the TEVAR group was significantly greater than that of the BMT group (TEVAR: 94.1% at 5 years, BMT: 86.1% at 5 years, P = .044). Multivariable Cox-hazard regression analysis demonstrated that the older age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.08, P = .013), BMT (HR, 2.33; 95% CI, 1.08-5.05, P = .032), and the distance between the primary entry tear and the left subclavian artery <2.0 cm (HR, 2.30; 95% CI, 1.06-4.99, P = .035) were the significant risk factors for all-cause death. Given death as a competing factor, the cumulative incidence of rupture in the BMT group was significantly greater than that of the TEVAR group (BMT: 13.7% at 5 years, TEVAR: 5.1% at 5 years, P = .024). CONCLUSIONS: Despite more complications in the early stage, TEVAR was associated with decreased risk of late death and had fewer late aortic ruptures compared with BMT in patients with acute uncomplicated TBAD. Therefore, TEVAR may be considered as the first option to improve the late outcomes in these patients.