Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE may not benefit from repeated TACE treatment. Our primary objective was to assess the diagnostic value of inflammatory markers in identifying early TACE refractory for patients with early (BCLC 0 and A) or intermediate (BCLC B) stage HCC. We retrospectively reviewed the HCC patients who underwent TACE as the initial treatment in two hospitals. Patients with early TACE refractoriness had significantly poorer median overall survival (OS) (16 vs 40 months, P<0.001) and progression-free survival (PFS) (7 vs 23 months, P<0.001) compared to TACE non-refractory patients. In the multivariate regression analysis, tumor size (P<0.001), bilobular invasion (P=0.007), high aspartate aminotransferase-to-platelet ratio index (APRI) (P=0.007), and high alpha fetoprotein (AFP) level (P=0.035) were independent risk factors for early TACE refractoriness. The predictive model showcasing these factors exhibited high ability proficiency, with an area under curve (AUC) of 0.833 (95%CI=0.774-0.892) in the training cohort, 0.750 (95%CI: 0.640-0.861) in the internal-validation cohort, and 0.733 (95%CI: 0.594-0.872) in the external-validation cohort. Calibration curve analysis revealed good agreement between the actual and predicted probabilities of early TACE refractoriness. Our preliminary study estimated the potential value of inflammatory markers in predicting early TACE refractoriness and provides a predictive model to assist in identifying patients who may not benefit from repeat TACE treatment. (TACE BCLC . (HCC) However A B hospitals OS (OS 16 (1 4 months P<0.001 P0001 P 001 progressionfree progression free PFS (PFS 7 ( 2 nonrefractory non P<0.001, , (P<0.001) P=0.007, P0007 P=0.007 007 (P=0.007) aminotransferasetoplatelet aminotransferase platelet APRI (APRI AFP (AFP P=0.035 P0035 035 (P=0.035 proficiency AUC (AUC 0833 833 0.83 95%CI=0.7740.892 95CI07740892 CI 95%CI=0.774 0.892 95 774 892 (95%CI=0.774-0.892 cohort 0750 750 0.75 95%CI 95CI (95%CI 0.6400.861 06400861 0.640 0.861 640 861 0.640-0.861 internalvalidation internal validation 0733 733 0.73 0.5940.872 05940872 0.594 0.872 594 872 0.594-0.872 externalvalidation external (HCC 1 P<0.00 P000 00 (P<0.001 P=0.00 (P=0.007 P=0.03 P003 03 (P=0.03 083 83 0.8 7740 95%CI=0.7740.89 95CI0774089 95CI0774 95%CI=0.77 0892 0.89 9 77 89 (95%CI=0.774-0.89 075 75 0.7 6400 0.6400.86 0640086 0640 0.64 0861 0.86 64 86 0.640-0.86 073 73 5940 0.5940.87 0594087 0594 0.59 0872 0.87 59 87 0.594-0.87 P<0.0 P00 (P<0.00 P=0.0 (P=0.00 (P=0.0 08 8 0. 95%CI=0.7740.8 95CI077408 95CI077 95%CI=0.7 089 (95%CI=0.774-0.8 07 0.6400.8 064008 064 0.6 086 6 0.640-0.8 0.5940.8 059408 059 0.5 087 5 0.594-0.8 P<0. P0 (P<0.0 P=0. (P=0. 95%CI=0.7740. 95CI07740 95CI07 95%CI=0. (95%CI=0.774-0. 0.6400. 06400 06 0.640-0. 0.5940. 05940 05 0.594-0. P<0 (P<0. P=0 (P=0 95%CI=0.7740 95CI0 95%CI=0 (95%CI=0.774-0 0.6400 0.640-0 0.5940 0.594-0 P< (P<0 P= (P= 95%CI= (95%CI=0.774- 0.640- 0.594- (P< (P (95%CI=0.774 (95%CI=0.77 (95%CI=0.7 (95%CI=0. (95%CI=0 (95%CI=

ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P<0.05). Th cells were screened by cell flow. The level of m 6A RNA methylation in the FTO knockdown group was significantly higher than in the vulnerable plaque group and empty load group (P<0.05). The levels of total cholesterol, triglyceride, and low-density lipoprotein C were higher at the 12th week than at the 1st week, but the high-density lipoprotein C level was lower at the 12th week than at the 1st week. At the 12th week, the interleukin-7 level was significantly lower in the adeno-associated virus-9 (AVV9)-FTO short hairpin RNA group than in the control and AVV9-green fluorescent protein groups (P<0.001). Conclusion: After successfully establishing a vascular parkinsonism rabbit model, m 6A RNA methylation can decrease Th cells and vulnerable atherosclerotic plaques. Introduction obesityassociated obesity associated (FTO N6methyladenosine Nmethyladenosine N6 methyladenosine N (RNA Methods 5 highfat high 10 (1 rabbits/group. rabbitsgroup rabbits/group . rabbits/group) Results (Th P<0.05. P005 P P<0.05 0 05 (P<0.05) flow cholesterol triglyceride lowdensity low density th st highdensity interleukin7 interleukin 7 interleukin- adenoassociated adeno virus9 virus 9 virus- AVV9FTO AVVFTO AVV9 AVV AVV9green AVVgreen green P<0.001. P0001 P<0.001 001 (P<0.001) Conclusion model plaques 1 ( P00 P<0.0 (P<0.05 P000 P<0.00 00 (P<0.001 P0 P<0. (P<0.0 (P<0.00 P<0 (P<0. P< (P<0 (P< (P

Abstract Objectives Cardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients. Methods A total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis. Results Higher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962–31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis. Conclusions Serum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis. Key Points Among all the cardiac biomarkers, the serum levels of hs-cTnI were independently associated with cardiac involvement in IIM patients. The serum levels of hs-cTnI were significantly correlated with disease activity in IIM patients. The abnormal hs-cTnI levels were correlated with poor prognosis in IIM patients. (IIM However Here 14 Immunology 201 202 study characteristics tests recorded measures test analysis highsensitivity sensitivity hscTnI hs cTnI (hs-cTnI n 41 adjusted 7810 7 810 7.81 95 (95 CI 1.962–31.097 196231097 1 962 31 097 1.962–31.097) 0.004, 0004 0.004 , 0 004 0.004] 0848 848 0.848 0.772,0.924 07720924 772 924 0.001. 0001 0.001 . 001 0.001) Besides Moreover 20 4 781 81 7.8 9 (9 1.962–31.09 19623109 96 3 09 000 0.00 00 084 84 0.84 0.772,0.92 0772092 77 92 2 78 8 7. ( 1.962–31.0 1962310 0.0 08 0.8 0.772,0.9 077209 1.962–31. 196231 0. 0.772,0. 07720 1.962–31 19623 0.772,0 0772 1.962–3 1962 0.772, 077 1.962– 196 0.772 07 1.962 19 0.77 1.96 0.7 1.9 1.

Abstract A HA_Cart_AdaBoost model is proposed to clean the data in drinking-water-quality data. First, the data that do not follow the normal distribution are regarded as outliers and eliminated. Next, the optimal control theory of nonlinear partial differential equations (PDEs) is introduced into the cart decision tree, and the cart decision with the specified depth is used. As a weak classifier of AdaBoost, the tree uses the HA_Cart_AdaBoost model to compensate for the eliminated data, then it fits and predicts the missing values of the data stream, realizes the cleaning of drinking-water-quality data, and finally uses the big data Hadoop architecture for real-time storage and analysing streaming data. The experimental results show that compared with the most advanced data cleaning methods, after the optimal control theory of nonlinear PDEs is introduced into the cart decision tree, the stability and accuracy of the HA_Cart_AdaBoost model for water quality data cleaning are greatly improved. Taking pH as an example, the HA_Cart_AdaBoost model shows a minimum improvement of 2.25% and a maximum improvement of 53.33% in terms of RMSE, and a minimum improvement of 13.51% and a maximum improvement of 78.08% in terms of MAE. HACartAdaBoost HA Cart AdaBoost drinkingwaterquality drinking First Next (PDEs used stream realtime real time methods improved example 225 2 25 2.25 5333 53 33 53.33 RMSE 1351 13 51 13.51 7808 78 08 78.08 MAE 22 2.2 533 5 3 53.3 135 1 13.5 780 7 0 78.0 2. 53. 13. 78.

ABSTRACT Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

Abstract Oridonin, a terpenoid with various biological functions, has limited uses in the functional food and pharmaceutical industries owing to its low water solubility. Previous studies have used cyclodextrin inclusion to improve its solubility. Herein, the effects of different cyclodextrins on the inclusion of oridonin were investigated using phase solubility and molecular docking tests. The binding constants of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin with oridonin were 22.6, 298.6, and 317.4, respectively. The corresponding binding energies were -6.49, -6.76, and -7.53 kcal/mol, respectively, suggesting that the interaction between γ-cyclodextrin and oridonin was the strongest, thereby improving the solubility of oridonin to the greatest extent. Further experiments indicated that no new unsaturated bonds formed after oridonin complexed with γ-cyclodextrin. In addition, the complexation of oridonin with γ-cyclodextrin, led to its complete dispersal in an amorphous state that was thermally stable. This study promotes the application of oridonin in food and medicines.

Abstract The modification of zein with sodium trimetaphosphate (STMP) as a cross-linking agent was studied. The effects of the mass ratio of STMP to zein (RS/Z), pH, reaction temperature and time on the rheological properties of modified zein solution (Z-SP) were evaluated. By using response surface methodology, the optimal modification conditions were also determined as following: RS/Z 0.03, pH 6.8, reaction time 2 h, reaction temperature 25 °C. Under these conditions, the observed shear stress of Z-SP solution was 35.0025 Pa, close to the predicted value. Compared with natural zein, the viscosity of Z-SP increased with the increasing shear rate, which was attributed to the structural changes, as evidenced by circular dichroism (CD) and Fourier transform infrared (FT-IR) analysis.

Abstract As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have been attracting increasing attention in recent years. Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure, and possesses many biological activities. However, its clinical application is significantly limited mainly due to its low oral bioavailability caused by poor hydrophilicity. To address this, ISL nanocrystals were developed in this study to improve its oral bioavailability. Three types of nanocrystals with differing particle size; R1, R2, and R3, were prepared by anti- solvent precipitation or anti-solvent precipitation combined with sonication, which was optimized by single-factor experiments. These nanocrystals were characterized based on their physical properties, in vitro release, and in vivo absorption performance. The mean particle size of R1, R2, and R3 was 555.7, 271.0, and 46.2, respectively. The dissolution ratio of ISL in the nanocrystals was significantly improved, with the quickest rate recorded in R2. Peak concentration and area under the concentration-time curve of R2 after oral administration in rats was 5.83- and 2.72-fold higher than that of the ISL solution, respectively. These findings indicate that the dissolution and absorption of ISL can be significantly enhanced by nanocrystals, and the dissolution behavior and pharmacokinetic properties of nanocrystals is significantly influenced by particle size. watersoluble water soluble drugs years (ISL structure activities However hydrophilicity R1 R anti antisolvent sonication singlefactor single factor experiments release performance 5557 555 7 555.7 2710 271 0 271.0 462 46 2 46.2 respectively improved concentrationtime time 5.83 583 5 83 2.72fold 272fold fold 2.72 72 solution 55 555. 27 271. 4 46. 5.8 58 8 72fold 272 2.7 5. 2.

Abstract Using fig leaves as raw materials, extraction time, extraction temperature, solid to liquid ratio, and ultrasonic power were selected as influencing factors to analyze their effects on the yield of fig leaf polysaccharides (FLPS). The response surface methodology was carried out to optimize the extraction parameters. Furthermore, the antioxidant activity of FLPS was studied. The experimental results show that the optimum extraction conditions are: extraction time of 121 min, extraction temperature of 72 °C, solid to liquid ratio of 1: 48 g/mL, and ultrasonic power of 250 W. In this case, the measured extraction rate of FLPS was 11.78%, which was in agreement with the theoretical extraction rate. Response surface analysis was used to accurately and reliably optimize the extraction of FLPS. The results of the antioxidant activity showed that FLPS had antioxidant activity. It has the best scavenging effect on ABTS radical cation (ABTS+·), and it also has ability to scavenge DPPH radical (DPPH·), hydroxyl radical (·OH), superoxide anion radical (·O2-), and ferric reducing activity. This study laid a theoretical foundation for the further development and application of FLPS.

Abstract The occurrence of zearalenone is considered a major risk factor affecting human and animal health worldwide. Zearalenone-contaminated feed can cause serious disorders and diseases in farm animals. A number of approaches have been developed to counteract zearalenone, but only few can be used. A potential approach to protecting animals against the harmful effects of zearalenone-contaminated feed is the use of substances to reduce zearalenone contamination of feed. The present study aimed to evaluate the effect of different absorbents in zearalenone-contaminated feed via in vitro bionic digestion. The results revealed that three types of absorbents exhibit improved effects. More than 50% of zearalenone is absorbed during digestion. Specifically, KLX (the main component is yeast cell wall), absorbed 83% of the zearalenone in the contaminated feed after bionic digestion in vitro. Monogastric animal bionic digestion is a rapid and physiologically relevant method to evaluate the efficacy of adsorbent materials in binding mycotoxins. The technique can be used to pre-screen the mycotoxin/adsorbent combinations as an alternative to animal experiments.

OBJECTIVES: This study assessed the protective effect of calcium dobesilate against contrast-induced nephropathy (CIN) after coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with diabetes and chronic kidney disease (CKD). METHODS: A total of 130 patients with diabetes and CKD estimated glomerular filtration rate: 30-90 mL/min/1.73m2 were enrolled and included in the analysis. They were divided into experimental (n=65) and control groups (n=65). Patients in the experimental group were administered oral calcium dobesilate (500 mg) three times daily for 2 days before and 3 days after the procedure. The serum creatinine (SCr), cystatin C (Cys C), and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured before and after the procedure. RESULTS: The mean SCr level at 24h after the procedure was found to be significantly lower in the experimental group than in the control group (79.1±19.6 μmol/L vs. 87.0±19.3 μmol/L, p=0.023). However, the Cys C and NGAL levels were not significantly different between the two groups at all measurement time points (all p>0.05). The incidence of CIN defined by the SCr level was significantly lower in the experimental group than in the control group (3 [4.6%] vs. 13 [20.0%], p=0.017). However, the incidence of CIN defined by the Cys C level was not statistically different between the two groups (7 [10.8%] vs. 7 [10.8%], p=1.000). CONCLUSIONS: This study revealed that calcium dobesilate has no preventive effect against CIN in patients with diabetes and CKD.

ABSTRACT Hybrid rice seeds from sterile lines have displayed a new type of heavy chalkiness in the subtropical zone of China in recent years, which was named top-gray chalkiness, resulting in a lower quality of hybrid rice seeds in large-scale production. In this study, the morphological characteristics of the chalky hybrid rice seeds were investigated, the microscopic structures of their chalky parts observed, the α-amylase activit and relative nutrient content analyzed, and the germination indexe and microorganism populations of the chalky hybrid seeds determined. The results revealed that top-gray chalkiness in hybrid rice seeds originated from the top site of the grain, and that the chalky part was probably infected by bacteri and fungi to form a gray colo and which further resulted in a lower germination rat and germination potential. This observed chalkiness in rice seeds differed from the previously reported rice chalkiness categories both in the occurrence positio and color. Besides, the amylopectin content declined in the chalky par and the protein content in the chalky part increased as compared to the normal seeds. This research could provide technical support for the hybrid rice breeding enterprises during the breeding of hybrid rice seeds in large-scale production.

The O2 adsorption and dissociation on M-doped (M=Al, Ag, W) Cu (111) surface were studied by density functional theory. The adsorption energy of adsorbate, the average binding energy and surface energy of Cu surface, and the doping energy of doping atom were calculated. All the doped atoms can be stably combined with Cu atoms and improve the surface activity of Cu surface, while the Al and W atoms would strengthen the bonding effect between the atoms on the Cu (111) slab except Ag doping atom. Due to the different electronegativity of three metals of Al, Ag, W, these doping atoms can resist the dissociation of O2 by DOS analysis. The potential energy surface was computed, and the result showed that the dissociation reaction of O2 on the surfaces not only reflected in the barrier energy, but also the reaction energy. Ag atoms had the best resistance effect on the O2 dissociation comparing with Al and W atoms because of the large barrier energy and reaction energy.

Abstract Background: Emerging evidence showed that microRNAs (miRs) play critical roles in human cancers by functioning as either tumor suppressor or oncogene. MIR-382 was found to function as tumor suppressor in certain cancers. However, the role of MIR-382 in colorectal cancer (CRC) is largely unknown. Specificity protein 1 (SP1) is highly expressed in several cancers including CRC and is correlated with poor prognosis, but it is unclear whether or not MIR-382 can regulate the expression of SP1. Methods: MIR-382 expression level was measured by reverse transcription-quantitative polymerase chain reaction. The connection between MIR-382 and SP1 was validated by luciferase activity reporter assay and western blot assay. Cell counting kit-8 assay and wound-healing assay were conducted to investigate the biological functions of MIR-382 in CRC. Results: In this study, we found MIR-382 expression was downregulated in CRC tissues and cell lines, and the transfection of MIR-382 mimic decreased cell growth and migration. Furthermore, we identified SP1 was a direct target of MIR-382. Overexpression of MIR-382 decreased the expression of SP1, whereas MIR-382 knockdown promoted SP1 expression. We also observed an inversely correlation between MIR-382 and SP1 in CRC tissues. Additionally, we showed that knockdown of SP1 inhibited cell growth and migration and attenuated the effect of MIR-382 inhibitor on cell behaviors. Conclusions: In conclusion, the present study describes a potential mechanism underlying a MIR-382/SP1 link contributing to CRC development. Thus, MIR-382 may be able to be developed as a novel treatment target for CRC.

The aim of this study was to evaluate the benefits and risks of omega-3 fatty acid supplementation in patients with chronic kidney disease. A systematic search of articles in PubMed, Embase, the Cochrane Library, and reference lists was performed to find relevant literature. All eligible studies assessed proteinuria, the serum creatinine clearance rate, the estimated glomerular filtration rate, or the occurrence of end-stage renal disease. Standard mean differences with 95% confidence intervals for continuous data were used to estimate the effects of omega-3 fatty acid supplementation on renal function, as reflected by the serum creatinine clearance rate, proteinuria, the estimated glomerular filtration rate, and relative risk. Additionally, a random-effects model was used to estimate the effect of omega-3 fatty acid supplementation on the risk of end-stage renal disease. Nine randomized controlled trials evaluating 444 patients with chronic kidney disease were included in the study. The follow-up duration ranged from 2 to 76.8 months. Compared with no or low-dose omega-3 fatty acid supplementation, any or high-dose omega-3 fatty acid supplementation, respectively, was associated with a lower risk of proteinuria (SMD: -0.31; 95% CI: -0.53 to -0.10; p=0.004) but had little or no effect on the serum creatinine clearance rate (SMD: 0.22; 95% CI: -0.40 to 0.84; p=0.482) or the estimated glomerular filtration rate (SMD: 0.14; 95% CI: -0.13 to 0.42; p=0.296). However, this supplementation was associated with a reduced risk of end-stage renal disease (RR: 0.49; 95% CI: 0.24 to 0.99; p=0.047). In sum, omega-3 fatty acid supplementation is associated with a significantly reduced risk of end-stage renal disease and delays the progression of this disease.