Calycosin action against atherosclerosis: integrating network pharmacology and in-silico investigation.

Atherosclerosis, caused by lipid deposit in the arterial wall for narrowing the arteries, is an increased risk factor of developing heart failure. Presently, clinical first-line drug therapy can be found with side effects, and thus new substitute medication should be developed needfully. Calycosin is one of the most bioactive products refined from natural plant, and it exerts promising cardiovascular protective effect. However, the pharmacological mechanisms of calycosin against atherosclerosis have not been elaborated. In this study, a systematic network pharmacology combined with molecular docking analysis was used to reveal the interaction activity and biological target in calycosin against atherosclerosis. We screened all preparative targets linked to calycosin and atherosclerosis from the available public databases. These results indicated total 409 putative targets in calycosin action, 71 of which were interacted with atherosclerosis. Further biological docking analysis suggested that calycosin displayed the powerful binding affinities with target proteins, including interleukin-6 (IL6) and mitogen-activated protein kinase 3 (MAPK3) MAPK3. Then enrichment findings revealed that calycosin action to treat atherosclerosis might be related to inhibition of inflammatory reaction and oxidative stress through modulating nucleolus transcription factor for improving lipid metabolism. In conclusion, the anti-atherosclerotic targets and molecular mechanisms in calycosin action were revealed systematically through preclinical evaluation. And calycosin may be a potential natural compound for the treatment of atherosclerosis.

N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1.

BACKGROUND: Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC. METHODS: CircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs. RESULTS: Herein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients. CONCLUSIONS: Taken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC.

A WHO digital intervention to address depression among young Chinese adults: a type 1 effectiveness-implementation randomized controlled trial.

Common mental disorders among young people are rising globally. Current university-based interventions are inadequate to address the need for evidence-based interventions. We investigated the effectiveness and implementation of Step-by-Step (SbS), a WHO digital intervention to address depression, among Chinese university students with depressive symptoms. In this paper, we report a type 1 hybrid effectiveness-implementation randomized controlled trial conducted between September 2021 and September 2022. The control condition was enhanced treatment as usual (ETAU, psychoeducation). The primary outcome was improvement in depression symptoms. Secondary outcomes were improvements in psychological well-being, anxiety symptoms, and self-identified psychosocial problems. Effectiveness of the intervention was evaluated using generalized linear mixed models. Implementation outcomes were evaluated by thematic analysis of participant interviews. A total of 371 participants were enrolled to two treatment conditions in a 1:1 ratio. SbS resulted in a greater reduction in depressive symptoms at posttreatment (p = 0.004, Hedges' g = 0.35), but no significant difference between SbS and ETAU was observed at three-month follow-up (p = 0.179, Hedges' g = 0.16). The treatment effect was larger among those who adhered to the treatment (Hedges' gs = 0.59 and 0.30). Subjective well-being also improved for SbS at both time points (Hedges' gs = 0.31 and 0.30). In addition, SbS resulted in more improvement in anxiety symptoms at posttreatment (p = 0.029, Hedges' g = 0.26), but not at three-month follow-up (p = 0.265, Hedges' g = 0.13). The qualitative results demonstrated that the intervention was well-implemented as a self-help mental health service, with minimal support from peer supporters. In conclusion, Step-by-Step, a digital intervention developed by WHO, was effective in reducing depressive symptoms in the short term and improving psychological well-being in a longer term. The sustained effect on depression needs further investigation. Improving uptake and engagement in the program is needed for its scale-up implementation as a university-based mental health service for Chinese young adults. Trial registration: ChiCTR2100050214.

Celecoxib and cisplatin dual-loaded microspheres synergistically enhance transarterial chemoembolization effect of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is a first-line treatment for intermediate to advanced-stage liver cancer, with drug-eluting microspheres commonly used as embolic agents. However, currently available drug-eluting microspheres suffer from low drug-loading capacity and limited drug options. In this work, we developed polydopamine-modified polyvinyl alcohol dual-drug-loaded microspheres encapsulating celecoxib and cisplatin (referred to as PCDMS). Physicochemical characterization revealed that the surface of the microspheres displayed increased roughness after polydopamine modification, and celecoxib and cisplatin were successfully loaded onto the microsphere surface. In vitro cell experiments demonstrated that the PCDMS significantly inhibited the proliferation and migration of highly metastatic human liver cancer cells (MHCC-97H) and human liver cancer cells (SMMC-7721). Furthermore, the dual-loaded microspheres exhibited remarkable tumor growth inhibition and reshaped the tumor microenvironment in both subcutaneous H22 liver cancer model in Balb/c mice and intrahepatic VX2 tumor model in New Zealand rabbits, demonstrating a synergistic antitumor effect where 1 + 1>2. This work provides a potential therapeutic approach for the treatment of refractory liver cancer and holds significant translational potential.

Paclitaxel-coated balloon catheter for benign esophageal stenosis in a rabbit model.

Most patients with benign esophageal stenosis require multiple or even continuous balloon dilation treatments to achieve symptom relief. In this study, eighteen rabbits were used to establish an esophageal benign stenosis model and were divided into a control group (n = 6), a balloon group (n = 6) and a PTX-coated balloon group (n = 6) to evaluate the feasibility and effectiveness of paclitaxel (PTX)-coated balloons for the rabbit esophageal benign stenosis model. The weight and esophageal diameter were recorded every 2 weeks until 8 weeks post-surgery. Hematoxylin-eosin staining, Masson's trichrome staining and immunohistochemical staining were performed for pathological analysis. Four weeks post-operation, there was a significant difference in weight between the control group and the balloon group (p = 0.01) and between the control group and the PTX balloon group (p = 0.01). There was a significant difference in the esophageal diameter between the balloon group and the PTX balloon group at 8 weeks post-operation (p = 0.02). Four weeks post-operation, the degree of inflammatory cell infiltration in the PTX balloon group was significantly lower than that in the control group (p = 0.002) and balloon group (p = 0.001). The degree of collagen deposition in the PTX balloon group was significantly lower than that in the control group (p = 0.002) and balloon group (p = 0.03). Eight weeks post-operation, the percentage of cells positive for TGF-ß (p < 0.001), the degree of inflammatory cell infiltration (p = 0.02) and the degree of collagen deposition (p = 0.02) in the PTX balloon group were significantly lower than those in the balloon group. Therefore, PTX-coated balloons may alleviate the local inflammatory response and collagen deposition when used during dilation treatment of benign esophageal stenosis.

Application of temperature-sensitive liquid embolic agent loaded with oxaliplatin in the TACE procedure for rabbit VX2 gastric cancer.

As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm3, 0.37 ± 0.11 cm3, and 1.19 ± 0.16 cm3, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.

[Spatial and Temporal Distribution Characteristics of Heavy Metals in Main Rivers Sediments and Ecological Risk Assessment in Kaifeng City].

Heavy metal pollution in urban river sediments is an important threat to river ecosystem health. To explore the temporal and spatial distribution characteristics of heavy metals in river sediments of Kaifeng City, the surface sediments of rivers were sampled in 2015 and 2021, respectively, and the contents of Cd, Cr, Cu, Ni, Pb, and Zn in sediments at different periods were compared. The heavy metal pollution in the two periods was evaluated using the indices of geo-accumulation, bio-toxicity risk assessment, and potential ecological risk. The results showed that the content of heavy metals in river sediments of Kaifeng City in 2021 were decreased significantly compared with that in 2015. Cd, Cr, Cu, Ni, Pb, and Zn decreased by 94.42%, 18.4%, 85.7%, 45.19%, 75.61%, and 92.28%, respectively. The heavy metal content in the Huafei River and Huiji River was higher than that in other rivers in both periods. Correlation and principal component analyses showed that the heavy metal pollution sources of river sediments in Kaifeng City were highly similar, and human activities such as industrial layout, road traffic, and land use were the main pollution sources. However, the results showed that the main pollutants were different between the two sampling times. In 2015, Cd, Cr, Pb, and Zn were the main pollutants, and in 2021, Cd, Cu, Pb, and Zn were the main pollutants. The results of the geo-accumulation, bio-toxicity risk assessment, and potential ecological risk indices showed that the temporal and spatial differences in heavy metal pollution in river sediments in Kaifeng City were large. However, the heavy metal pollution of the Huiji River and Huafei River was still serious, with contents in the medium and high pollution levels, especially to Cd. The heavy metal treatment of rivers in Kaifeng City has a long way to go, and it is particularly necessary to strengthen the engineering treatment for key river sections and effectively monitor key pollution elements.

Introducing activation functions into segmented regression model to address lag effects of interventions.

The interrupted time series (ITS) design is widely used to examine the effects of large-scale public health interventions and has the highest level of evidence validity. However, there is a notable gap regarding methods that account for lag effects of interventions.To address this, we introduced activation functions (ReLU and Sigmoid) to into the classic segmented regression (CSR) of the ITS design during the lag period. This led to the proposal of proposed an optimized segmented regression (OSR), namely, OSR-ReLU and OSR-Sig. To compare the performance of the models, we simulated data under multiple scenarios, including positive or negative impacts of interventions, linear or nonlinear lag patterns, different lag lengths, and different fluctuation degrees of the outcome time series. Based on the simulated data, we examined the bias, mean relative error (MRE), mean square error (MSE), mean width of the 95% confidence interval (CI), and coverage rate of the 95% CI for the long-term impact estimates of interventions among different models.OSR-ReLU and OSR-Sig yielded approximately unbiased estimates of the long-term impacts across all scenarios, whereas CSR did not. In terms of accuracy, OSR-ReLU and OSR-Sig outperformed CSR, exhibiting lower values in MRE and MSE. With increasing lag length, the optimized models provided robust estimates of long-term impacts. Regarding precision, OSR-ReLU and OSR-Sig surpassed CSR, demonstrating narrower mean widths of 95% CI and higher coverage rates.Our optimized models are powerful tools, as they can model the lag effects of interventions and provide more accurate and precise estimates of the long-term impact of interventions. The introduction of an activation function provides new ideas for improving of the CSR model.

Transcatheter arterial chemoembolization combined with apatinib and camrelizumab for unresectable advanced gastric or gastroesophageal junction cancer: a single-arm, single-center, retrospective study.

Purpose: This study aims to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with Apatinib and Camrelizumab for treating unresectable advanced gastric or gastroesophageal junction (G/GEJ) cancer. Material and methods: In this study, data of patients with unresectable advanced G/GEJ cancer who received TACE combined with Apatinib and Camrelizumab from August 2018 to December 2021 was evaluated. After TACE, patients were given intravenous Camrelizumab 200mg every three weeks and oral apatinib 250mg/day for treatment. The primary endpoint was overall survival (OS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: A total of 49 patients were enrolled in this study. The median follow-up time was 14.0 months, and the median OS was 20.0 months (95% CI = 13.6-26.4). Two patients (4.08%) achieved complete remission, 28 patients (57.14%) achieved partial remission, 18 patients (36.73%) had stable disease, and 1 patient (2.04%) had disease progression. The ORR was 61.22%, and the DCR was 97.96%. Multivariate Cox regression analysis indicated that age (HR 4.74, 95% CI = 1.674-13.440, P=0.003) and multiple distant metastases (HR 20.916, 95% CI = 4.094-106.808, P = 0.001) were independent risk factors for OS. Most AEs were classified as grade 1-2, the most common being RCCEP (69.39%). There were 5 cases of grade 3-4 adverse events (10.20%). No patients discontinued or reduced the treatment dose due to AEs, and all patients received symptomatic treatment. Conclusion: TACE combined with Apatinib and Camrelizumab is a safe and effective therapeutic option for patients with unresectable advanced G/GEJ cancer, which can significantly improve the median OS and ORR of patients. And the adverse events (AEs) are tolerable and manageable.

Percutaneous microwave ablation for lung tumors: a retrospective case-control study of conventional CT and C-arm CT guidance.

Background: Although conventional computed tomography (cCT) is the mainstream guidance equipment for lung microwave ablation (MWA), C-arm CT can provide 3-dimensional (3D) CT-like images reconstructed from 2-dimensional (2D) digital subtraction angiography (DSA) information within 8 seconds, highlighting its utility as a new guidance tool. This retrospective case-control study was performed to evaluate the clinical performance of percutaneous MWA for lung tumors using cCT and C-arm CT guidance. Methods: From April 2015 to April 2020, 101 consecutive patients with solitary lung tumors who underwent percutaneous MWA at our single center (Zhengzhou, China) were divided into 2 groups: the cCT group (n=56), with unarmed puncture, and the C-arm CT group (n=45), with iGuide navigation-assisted puncture. The primary endpoints were technical success, technical efficacy, puncture scoring (PS), and complete ablation (CA) rate. The secondary endpoints were complications, median progression-free survival (mPFS), and median overall survival (mOS). Results: The technical success rates were 100% in both the C-arm CT group and cCT group. The technical efficacies were 93.3% and 91.1% in the C-arm CT group and cCT group, respectively, with no statistical difference (P=0.67). The PS (2.9 vs. 2.5, P=0.02), total procedure time (TPT; 39.3 vs. 50.0 min, P<0.001), puncture time (PT; 12.6 vs. 15.7 min, P=0.001), and irradiation effective dose (ED; 15.2 vs. 20.9 mSV, P<0.001) showed significances between patients in the C-arm CT and those in the cCT group. The ablation time (AT; 9.1 vs. 9.6 min, P=0.36), CA rate (93.3% vs. 92.9%, P=0.93), local tumor progression (LTP) rate (11.1% vs. 8.9%, P=0.98), complications, mPFS (9.5 vs. 10.1 months, P=0.52), and mOS (37.9 vs. 38.8 months, P=0.67) showed no statistically significant difference between the 2 groups. Conclusions: C-arm CT guidance is as feasible and effective as cCT for lung tumor MWA, which can increase PS and decrease TPT.

Bevacizumab-loaded CalliSpheres beads: in vitro loading, release profiles and application in rabbit liver VX2 tumor model.

Background: Bevacizumab loaded drug-eluting beads have the potential to reduce TACE related VEGF expression. The purpose of this study was to investigate the in vitro loading, and release profiles of bevacizumab (BEV) loaded on Callispheres beads (CB) and its application in rabbit liver VX2 tumor model. Methods: CB with sizes of 100-300 um and 300-500 um were divided into 5 groups, respectively. BEV with different content was prepared for CB loading, releasing and detected in the solution at different time points. The diameters of CB in each group were measured under a light microscope to calculate the shrinkage rate. The rabbit with VX2 liver model were divided into control group, CB-TACE group, CB-TACE+BEV group, and BEV group. The data of blood test, CT image, HE and IHC staining were compared and analyzed. Results: The shrinkage rate of the 100-300 um CB was 2.6-7.2%, while the 300-500 um CB was 0.2-7.1%. The BEV-loaded CB (BEV-CB) has a burst release during the first hour and following gradually released with time. The release profiles of 100-300 um CB reach 34% in 24 hours, while the 300-500 um CB to 25.8%. BEV-CB with sizes of 100-300 um was chosen to perform transcatheter arterial chemoembolization (TACE). The results showed that BEV-CB-TACE not only gradually increased the content of BEV in serum and organ tissue but also reduced the level of VEGF in serum. Pathological results suggested that the expression of HIF-1 was elevated while VEGF and MVD decreased when compared to the other groups. Conclusion: In conclusion, this study confirms that Callispheres beads could efficiency loaded BEV. BEV-CB-TACE has a good safety and effectiveness, and its application could reduce the level of VEGF-A in serum in the treatment of VX2 tumors.

Optimized segmented regression models for the transition period of intervention effects.

BACKGROUND: The interrupted time series (ITS) design is a widely used approach to examine the effects of interventions. However, the classic segmented regression (CSR) method, the most popular statistical technique for analyzing ITS data, may not be adequate when there is a transitional period between the pre- and post-intervention phases. METHODS: To address this issue and better capture the distribution patterns of intervention effects during the transition period, we propose using different cumulative distribution functions in the CSR model and developing corresponding optimized segmented regression (OSR) models. This study illustrates the application of OSR models to estimate the long-term impact of a national free delivery service policy intervention in Ethiopia. RESULTS: Regardless of the choice of transition length ([Formula: see text]) and distribution patterns of intervention effects, the OSR models outperformed the CSR model in terms of mean square error (MSE), indicating the existence of a transition period and the validity of our model's assumptions. However, the estimates of long-term impacts using OSR models are sensitive to the selection of L, highlighting the importance of reasonable parameter specification. We propose a data-driven approach to select the transition period length to address this issue. CONCLUSIONS: Overall, our OSR models provide a powerful tool for modeling intervention effects during the transition period, with a superior model fit and more accurate estimates of long-term impacts. Our study highlights the importance of appropriate statistical methods for analyzing ITS data and provides a useful framework for future research.

External beam radiotherapy inhibits stent related granulation hyperplasia in rabbit trachea.

Endobronchial stent exacerbates the formation of granulation tissue. Radiotherapy maybe a durable treatment option for granulation hyperplasia. In this study, we explore the results of external beam radiotherapy (EBRT) for granulation hyperplasia after airway stent placement. A total of 30 New Zealand rabbits were assigned in three groups, Control group (n = 12), low dosage (LD, 12 Gy in 4 fractions and twice a week) group (n = 9) and high dosage (HD, 20 Gy in 4 fractions and twice a week) group (n = 9). Post-stenting 1 week, LD and HD group started to receive EBRT. Bronchoscopy, Haematoxylin-eosin (HE), Masson's trichrome (MTS), Safranin O (SO) and immunohistochemical (IHC) staining protocols were performed to evaluate the histopathological changes of trachea. A total of 30 stents were successfully implanted in 30 rabbits. No procedure-related death and complications happened. Post-stenting 4 w, 8 w and 12 w, the ventilate area ratio (VAR) and qualitative histological scoring (QHS) in the LD group and HD group lower than the Control group. Post-stenting 12w, the immunohistochemical results revealed that the positive percentage of TGF-ß and VEGF in the LD group and HD group were lower than the Control group. In conclusion, the present study investigated the efficacy of EBRT in reducing stent related granulation tissue formation in the rabbit trachea. Higher dosage EBRT with a better result in inhibiting granulation hyperplasia.

125I brachytherapy: a useful treatment to control painful osteoblastic bone metastases

Backgrounds 125I brachytherapy is effective in relieving cancer pain due to osteolytic bone metastases. However, fewer studies focused on painful osteoblastic bone metastases (OBMs), we conducted a retrospective study to evaluate the efficacy of 125I brachytherapy for the treatment of painful OBMs. Methods From April 2017 to April 2019, clinical data of a total of 65 patients with OBMs who underwent CT/cone beam CT -guided 125I brachytherapy were collected and analyzed. The primary study endpoints were technical success, relief of pain (RoP), and quality of life (QoL). The secondary study endpoints were treatment-related complications, local tumor control (LCR), and overall survival (OS). The logistic regression analysis was performed to predict RoP. Results Technical success rate was 100%. Visual analog scale scores and daily morphine consumption continuously decreased significantly at 2 weeks, 6 weeks, and 10 weeks (all P < 0.05). The RoP at 6 weeks was 84.62%. QoL presented improvement at 6 and 10 weeks. Only minor complications occurred in 12 patients (18.46%). LCR was 93.85% at 10 weeks. The OS was 29.80 months. Two factors were significantly associated with the RoP: max diameter (MD, < 3 cm vs. ≥ 3 cm, P = 0.019) and serum levels of bone alkaline phosphatase (B-ALP, ≥ 100 U/L vs. < 100 U/L, P = 0.016). Conclusions 125I brachytherapy is an effective treatment in relieving painful OBMs and improving patients’ QoL (AU)

Association of long-term exposure to ambient PM2.5 and its constituents with gut microbiota: Evidence from a China cohort.

Accumulating animal experiments and epidemiological studies have found that exposure to fine particulate matter (PM2.5) is associated with altered gut microbiota (GM). However, it is unclear what kind of role the PM2.5 constituents play in the PM2.5-GM association. Therefore, this study aimed to investigate the association of long-term exposure to PM2.5 and its constituents (PMcons) with GM. This study included 1583 participants from a cohort in Southwest China. Satellite remote sensing and chemical transport modelling were used to determine the yearly average concentrations of PMcons. GM data were derived from 16 s sequencing based on stool samples. Generalized propensity score weighting regression and Bayesian Kernel Machine Regression (BKMR) were used to estimate the individual and joint association of exposure to PMcons with the Shannon index. The weighted correlation analysis was used to estimate the association of PMcons with the composition of GM. The result showed that an interquartile range increase of 3-year average black carbon (BC), ammonium, nitrate, organic matter (OM), sulfate, and soil particles (SOIL) were negatively associated with Shannon index with mean difference (95 % confidence interval) being -0.144 (-0.208, -0.080), -0.141 (-0.205, -0.078), -0.126 (-0.184, -0.068), -0.117 (-0.172, -0.062), -0.153 (-0.221, -0.085), and - 0.153 (-0.222, -0.085). BKMR indicated joint exposure to PMcons was associated with decreased Shannon index, and BC had the largest posterior inclusion probability (0.578). Weighted correlation analyses indicated PMcons were associated with decreased Bacteroidetes (r = -0.204, P < 0.001 for PM2.5) and increased Proteobacteria (r = 0.273, P < 0.001 for PM2.5). These results revealed that long-term exposure to PMcons was associated with GM. BC was the most important constituent in the association, indicating that the source of BC should be controlled to mitigate the negative effects of PM2.5 on GM.

Positron emission tomographic studies of the association between atherogenesis and aortitis among psoriatic patients.

Introduction: There is increased interest in the use of positron emission tomography (PET) in psoriatic patients. We used PET induced with tracer fluorine-18 (18F) fluorodeoxyglucose (FDG) to study the association between the process of early-atherogenesis (eAg) and aortitis by quantifying enhanced aortic vascular inflammation along with calculation of total coronary plaque load (TCPL) and non-calcified atherosclerotic plaque load (NcAPL). In order to study the utility of aortitis in capturing eAg, we also assessed luminal stenosis atherosclerosis (LSA) and high-risk coronary plaques (HrCP). Material and methods: The study was conducted at our hospital between 1 April 2014 and 31 December 2017, and the analysis was done in July 2018. We recruited 180 consecutive psoriatic patients and subjected them to 18F-FDG PET. However, in order to characterise eAg, 160 out of 180 patients were also subjected to coronary angiographic computed tomographic studies (CACTS). Results: Among 180 psoriatic patients (76 women, 42%) (mean [SD] age, 51.1 [13.2] years), greater prevalence values of LSA (odd ratio [OR], 3.71; 95% confidence interval [CI], 1.84-7.89; p = 0.001) and HrCP (OR, 3.11; 95% CI: 1.54-6.51; p = 0.003) along with enhanced TCPL (standardised ß = 0.44; p < 0.001) were observed in patients with enhanced aortitis. However, the association between aortitis and HrCP was controlled by low-attenuation plaque (LAP), while the same between aortitis and TCPL was controlled by NcAPL (ß = 0.45; p < 0.001). Conclusions: Association between aortitis and broad coronary angiographic indices was achieved and hence predicted the possibility of a surrogate role of aortitis in eAg.

125I brachytherapy: a useful treatment to control painful osteoblastic bone metastases.

BACKGROUNDS: 125I brachytherapy is effective in relieving cancer pain due to osteolytic bone metastases. However, fewer studies focused on painful osteoblastic bone metastases (OBMs), we conducted a retrospective study to evaluate the efficacy of 125I brachytherapy for the treatment of painful OBMs. METHODS: From April 2017 to April 2019, clinical data of a total of 65 patients with OBMs who underwent CT/cone beam CT -guided 125I brachytherapy were collected and analyzed. The primary study endpoints were technical success, relief of pain (RoP), and quality of life (QoL). The secondary study endpoints were treatment-related complications, local tumor control (LCR), and overall survival (OS). The logistic regression analysis was performed to predict RoP. RESULTS: Technical success rate was 100%. Visual analog scale scores and daily morphine consumption continuously decreased significantly at 2 weeks, 6 weeks, and 10 weeks (all P < 0.05). The RoP at 6 weeks was 84.62%. QoL presented improvement at 6 and 10 weeks. Only minor complications occurred in 12 patients (18.46%). LCR was 93.85% at 10 weeks. The OS was 29.80 months. Two factors were significantly associated with the RoP: max diameter (MD, < 3 cm vs. ≥ 3 cm, P = 0.019) and serum levels of bone alkaline phosphatase (B-ALP, ≥ 100 U/L vs. < 100 U/L, P = 0.016). CONCLUSIONS: 125I brachytherapy is an effective treatment in relieving painful OBMs and improving patients' QoL.

miR-375 suppresses the growth and metastasis of esophageal squamous cell carcinoma by targeting PRDX1.

Background: Esophageal cancer (EC) is one of the most lethal cancers. Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype in Asian people. Diverse microRNAs, such as miR-375, have been confirmed to be involved in the process of tumorigenesis and metastasis. However, the underlying mechanism through which miR-375 acts in ESCC patients remains unknown. Methods: We used The Cancer Genome Atlas (TCGA) database to analyze the association between miR-375 and the survival rate in patients with esophageal squamous cell carcinoma. Real Time quantitative PCR (RT-qPCR) analysis was performed to evaluate the level of miR-375 in EC tissues and cells. A luciferase reporter assay was used to confirm the target gene of miR-375. A colony formation assay as well as flow cytometric and transwell invasion experiments were employed to examine the effects of miR-375 and peroxiredoxin 1 (PRDX1) on ESCC cells. A tumor xenograft mouse model was then used to investigate the role of miR-375 on tumor growth in vivo. Moreover, we performed rescue experiments to evaluate the effect of PRDX1 on ESCC progression. Results: miR-375 expression was significantly downregulated in both ESCC clinical tissues and serum, and the reduction of miR-375 was remarkably linked to a poor prognosis in ESCC. Further investigation illustrated that aberrant expression of miR-375 dampened the growth and infiltration of ESCC cells both in vitro and in vivo. Bioinformatics and luciferase reporter analysis verified that the transcript of PRDX1 is a direct target of miR-375 and its expression in ESCC cells was found to be inversely modulated by miR-375. Moreover, the tumor formation experiment in nude mice confirmed that miR-375 can effectively dampen tumor growth in xenograft tumor mice models. Notably, over-expression of PRDX1 effectively counteracted the tumor-suppressing capabilities of miR-375. Conclusions: We demonstrated the antitumor effect of miR-375 on ESCC by targeting PRDX1 both in vitro and in vivo.

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization.

BACKGROUND: Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. METHODS: Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-ß and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. RESULTS: Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). CONCLUSIONS: In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.