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To develop a monitoring model using radiomics analysis based on longitudinal B-mode ultrasound (BUS) and shear wave elastography (SWE) to early predict pathological response to neoadjuvant chemotherapy (NAC) in breast cancer patients. In this prospective study, 112 breast cancer patients who received NAC between September 2016 and March 2022 were included. The BUS and SWE data of breast cancer were obtained prior to treatment as well as after two and four cycles of NAC. Radiomics features were extracted followed by measuring the changes in radiomics features compared to baseline after the second and fourth cycles of NAC (△R [C2], △R [C4]), respectively. The delta radiomics signatures were established using a support vector machine classifier. The area under receiver operating characteristic curve (AUC) values of △R BUS (C2) and △R BUS (C4) for predicting the response to NAC were 0.83 and 0.84, while those of △R SWE (C2) and △R SWE (C4) were 0.88 and 0.90, respectively. △R SWE exhibited significantly superior performance to △R BUS for predicting NAC response (Delong test, p < 0.01). No significant differences were observed in the performances between △R (C2) and △R (C4) based on BUS or SWE data. The longitudinal dual-modal ultrasound radiomics (LDUR) model had an excellent discrimination, good calibration and clinical usefulness, with the AUC, sensitivity and specificity of 0.97, 95.52% and 91.11%, respectively. The LDUR model achieved excellent performance in predicting the pathological response to chemotherapy during the early stages of NAC for breast cancer. [ABSTRACT FROM AUTHOR]

To carry out radiomics analysis/deep convolutional neural network (CNN) based on B-mode ultrasound (BUS) and shear wave elastography (SWE) to predict response to neoadjuvant chemotherapy (NAC) in breast cancer patients. In this prospective study, 255 breast cancer patients who received NAC between September 2016 and December 2021 were included. Radiomics models were designed using a support vector machine classifier based on US images obtained before treatment, including BUS and SWE. And CNN models also were developed using ResNet architecture. The final predictive model was developed by combining the dual-modal US and independently associated clinicopathologic characteristics. The predictive performances of the models were assessed with five-fold cross-validation. Pretreatment SWE performed better than BUS in predicting the response to NAC for breast cancer for both the CNN and radiomics models (P < 0.001). The predictive results of the CNN models were significantly better than the radiomics models, with AUCs of 0.72 versus 0.69 for BUS and 0.80 versus 0.77 for SWE, respectively (P = 0.003). The CNN model based on the dual-modal US and molecular data exhibited outstanding performance in predicting NAC response, with an accuracy of 83.60% ± 2.63%, a sensitivity of 87.76% ± 6.44%, and a specificity of 77.45% ± 4.38%. The pretreatment CNN model based on the dual-modal US and molecular data achieved excellent performance for predicting the response to chemotherapy in breast cancer. Therefore, this model has the potential to serve as a non-invasive objective biomarker to predict NAC response and aid clinicians with individual treatments. [ABSTRACT FROM AUTHOR]

Cross-sectional analyses showed that the prevalence of basal core promoter (BCP) double mutations (nt 1762T, 1764A) of hepatitis B virus (HBV) gradually increases with age. We aimed to determine the incidence rate of the mutations over 10 years. Study subjects were selected from the Long An cohort established in 2004, including 59 with HBV with single mutations at nt 1762 or 1764 in the BCP and 342 with wild type BCP sequences at baseline. Their serum samples for analysis were obtained at the 3rd and 10th annual visits, respectively. The results showed that the annual incidence rate of BCP double mutations is 3.8% (95% confidence interval [CI]: 1.4–6.2) and tends to decrease with age. The peak incidence is in the 30–34 years age-group. The incidence rate in HBeAg positive individuals (5.5%) is significantly higher than in those without HBeAg (3.4%) ( P < 0.05). The incidence rate is significantly higher in genotype C (4.8%) than in genotype B (2.8%) or I (3.1%). The incidence rate of the mutations (6.8%) developing from a single mutation at nt 1762 or 1764 is significantly higher than that (3.8%) from the wild type sequence ( P < 0.005). The difference in incidence of single mutations between nt 1762 (0.7%) and 1764 (0.03%) is significant ( P < 0.05). In conclusion, the incidence rate of BCP double mutations tends to decrease with age after the age of 35 years. Viruses with a single mutation at nt 1762 or 1764 are more prone to develop double mutations. Nt 1762 is the more common site of the first mutation. [ABSTRACT FROM AUTHOR]

Abstract: PLGA-microparticles with 4.7μm in diameter were prepared by the double emulsion technique and loaded with 1.7μg fluorescein/mg PLGA mimicking a hydrophilic API. In an effort to further elucidate the release and bioadhesive characteristics of lectin-grafted formulations in vitro, the particles were coated with wheat germ agglutinin. The microparticles exhibited thermo-responsive release since no free fluorescein was detected at 4°C or room temperature. At body temperature, however, more than 80% of the payload was released within 48h. The adhesion of lectin-grafted particles to Caco-2 monolayers, which were applied as a model for the human intestinal epithelium, exceeded that of plain ones 1.5-fold as also observed by fluorescence microscopy. Furthermore, the amount of model drug bound and taken up into the cells was 5.8-fold higher after incubation for 4h at 37°C as compared to fluorescein in solution. According to fluorescence imaging a considerable amount of the total fluorescein payload was accumulated intracellularily after incubation for 5h at 37°C. These findings not only confirm the utility of bioadhesives of the second generation for improved absorption of low molecular weight hydrophilic compounds but also indicate storage stability of such suspensions at 4°C and room temperature without any premature loss of API. [Copyright &y& Elsevier]

Abstract: Maggot debridement therapy plays an important role in treatment of diabetic foot ulcers and other chronic infectious wounds, cause of this is its extremely low drug resistance. However, the microbe stimulated maggot, we may call it a derivative of normal sterile maggot, could exhibit stronger bacterial or bactericidal effects. Methods of the pretreatment on maggot was different germ solution were artificially mixed and added with originally sterile maggots, the novel secretions were collected. Some of this have been demonstrated by plate test and telescope analysis. Thus, we hypothesize that maggot especially the larvae of Lucilia sericata was conducted as the germ irritant receptor, and diverse germs interacted with it, at last, novel secretions/excretions we got will offer a great help to the general surgery clinicians as well as researchers who are interested in novel antibiotics discovery. [Copyright &y& Elsevier]

Abstract: Aim of the study: Depression is a severe mood disorder. It was treated with Shudihuang, the steamed roots of Rehmannia glutinota Libosch. (SRG), in traditional Chinese medicine. The present paper was designed to verify its antidepressant effect. Materials and methods: A mouse model of depression was established though unpredictable chronic mild stress (UCMS). Low and high doses of SRG were administered orally. Fur state, body and organ weight, and gastric ulcers were examined. Locomotion was assayed in open field test. Liver antioxidant indexes were measured spectrophotometrically. Results: Fur state, body and organ weight were found to be insensitive to UCMS. The locomotion reduced by UCMS was restored by low dose of SRG (2.5g/kg BW) but not by high dose (5g/kg BW). UCMS resulted in aggravated gastric ulceration, elevated liver malondialdehyde, together with reduced total antioxidant capability, glutathione content, and superoxide dismutase and catalase activities. The alterations were improved by SRG in a dose-dependent manner. The differences in the activity of glutathione peroxidase were statistically nonsignificant among groups. Clomipramine the positive drug was similar to SRG especially in antioxidation. Conclusion: SRG is of therapeutic value for depression-like disorders, and antioxidation may be one of the mechanisms underlying its antidepressant action. [Copyright &y& Elsevier]

It has been reported that some mutations in the genome of hepatitis B virus (HBV) may predict the outcome of the virus infection. However, evolutionary data derived from long-term longitudinal analysis of entire HBV genomes using next generation sequencing (NGS) remain rare. In this study, serum samples were collected from asymptomatic hepatitis B surface antigen (HBsAg) carriers from a long-term prospective cohort. The entire HBV genome was amplified by polymerase chain reaction (PCR) and sequenced using NGS. Twenty-eight time series serum samples from nine subjects were successfully analysed. The Shannon entropy (S n) ranged from 0 to 0.89, with a median value of 0.76, and the genetic diversity (D) ranged from 0 to 0.013, with a median value of 0.004. Intrahost HBV viral evolutionary rates ranged from 2.39E-04 to 3.11E-03. Double mutations at nt1762(A → T) and 1764(G → A) and a stop mutation at nt1896(G → A) were seen in all sequences from subject BO129 in 2007. However, in 2019, most sequences were wild type at these positions. Deletions between nt 2920–3040 were seen in all sequences from subject TS115 in 2007 and 2013 but these were not present in 2004 or 2019. Some sequences from subject CC246 had predicted escape substitutions (T123N, G145R) in the surface protein in 2004, 2013 and 2019 but none of the sequences from 2007 had these changes. In conclusion, HBV mutations may revert to wild type in natural infection. Clinicians should be wary of predicting long-term prognoses on the basis of the presence of mutations. • Hepatitis B virus (HBV) may develop a lots of mutations when it replicate. • Some of HBV genetic mutations may predict the outcome of the virus infection. • Mutations in the genome of HBV may revert to wild type during the long-term evolution of the virus. [ABSTRACT FROM AUTHOR]

Background/Aims: Although there have been a few reports regarding the effect of basal core promoter (BCP) double mutations (A1762T and G1764A) on hepatitis B viral loads, the association remains uncertain. We aim to determine the association after controlling for HBeAg – a strong confounding factor. Methods: We selected randomly 190 individuals from a Chinese cohort of 2258 subjects for cross-sectional analysis and 56 of the 190 for longitudinal analysis of viral loads. Results: In multivariable analysis of the cross-sectional data, BCP double mutations are significantly associated with lower viral loads in HBeAg positive subjects but no difference was found in anti-HBe positive subjects. Triple mutations at nucleotide (nt) 1753, 1762 and 1764 and mutations between nt 1809 and 1817, precore stop mutation (nt 1896) and genotype are not associated with viral loads in either HBeAg or anti-HBe positive subjects. Analysis of the longitudinal data yielded similar results to the cross-sectional data. Viral loads differ significantly between individuals infected with wild-type and BCP double mutations prior to HBeAg seroconversion but this difference is lost after seroconversion. Conclusions: BCP double mutations are associated with lower viral loads in HBeAg positive individuals but have no effect on the viral loads of anti-HBe positive individuals. [Copyright &y& Elsevier]

Daidzein, a natural isoflavonoid found in Leguminosae, has received increasing attention because of its possible role in the prevention of osteoporosis. In the present investigation, primary osteoblastic cells isolated from newborn Wistar rats were used to investigate the effect of this isoflavonoid on osteoblasts. Daidzein (2–50 μM) increased the viability (P<0.05) of osteoblasts by about 1.4-fold. In addition, daidzein (2–100 μM) increased the alkaline phosphatase activity and osteocalcin synthesis (P<0.05) of osteoblasts by about 1.4- and 2.0-fold, respectively. Alkaline phosphatase and osteocalcin are phenotypic markers for early-stage differentiated osteoblasts and terminally differentiated osteoblasts, respectively. Our results indicated that daidzein stimulated osteoblast differentiation at various stages (from osteoprogenitors to terminally differentiated osteoblasts). We also investigated the effect of daidzein on bone morphogenetic protein (BMP) production in osteoblasts that display the mature osteoblast phenotype. The results indicated that BMP2 synthesis was elevated significantly in response to daidzein (the mRNA increased 5.0-fold, and the protein increased 7.0-fold), suggesting that some of the effects of daidzein on the cell may be mediated by the increased production of BMPs by the osteoblasts. In conclusion, daidzein has a direct stimulatory effect on bone formation in cultured osteoblastic cells in vitro, which may be mediated by increased production of BMPs in osteoblasts. [Copyright &y& Elsevier]

In slope reliability analysis, "local averaging" of the statistical soil parameters on the slope slip surface is the main factor influencing the results of the analysis. In this study, we analyzed the curvilinear local averaging of a 2-D random field by equation derivation based on random field theory and statistical analysis. By assuming a circular slip surface, the variance reduction due to curvilinear local averaging was obtained as a function of geometric characteristics of the slip surface and variance at a "point" level, and a simple reliability analysis method for homogeneous natural slope was proposed. The proposed method contains three major steps: statistical analysis of soil parameters by site tests, determination of the limit state curve using a series of deterministic finite element analyses, and the calculation of slope failure probability by integrating the probability density function corresponding to the limit state curve. A comparative analysis shows that the proposed slope reliability analysis method based on a curvilinear local averaging of a 2-D random field is reliable and efficient. [ABSTRACT FROM AUTHOR]