Objective:To explore the value of dual-layer detector spectral CT quantitative parameters in evaluating the treatment response of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The study was a cross-sectional study. From May 2021 to March 2023, a total of 52 patients with LARC who received complete nCRT and were pathologically confirmed rectal adenocarcinoma at the Guangdong Province Hospital of Traditional Chinese Medicine were retrospectively enrolled. Each patient underwent spectral CT examination before and after nCRT, including plain scan, arterial phase (AP), and venous phase (VP) scans. According to the tumor regression grade, the patients were divided into the good response ( n=20) and the poor response group ( n=32). Measurements of the primary tumor′s spectral CT parameters, including effective atomic number (Z eff) at plain scan, iodine concentration (IC), CT values of 40 keV and 100 keV virtual monochromatic image (VMI) at dual-enhanced phases, were taken before and after nCRT. Additionally, the normalized iodine concentration (NIC), spectral curve slope (λHU), and the change rate of the above parameters before and after nCRT were calculated. The independent sample t-test or Mann-Whitney U test was used to compare the differences between the two groups. The receiver operating characteristic (ROC) curve was used to assess the efficacy of various metrics in evaluating the tumor treatment response of nCRT. A binary logistic regression analysis of combined parameter results was performed for the parameters with the areas under curve (AUC)>0.75, and the AUC of the combined parameter was evaluated. Results:There were significant differences in NIC AP and λHU VP before nCRT, NIC VP and λHU VP after nCRT, and the change rates of Z eff, NIC AP, NIC VP and λHU AP between the good response group and the poor response group ( P<0.05). The remaining parameters showed no statistically significant difference ( P>0.05). The ROC curve results showed that the AUCs of the above 8 parameters for evaluating tumor treatment response of nCRT were 0.702, 0.655, 0.695, 0.769, 0.738, 0.807, 0.791, and 0.677, respectively. The AUC of the combined model of the three parameters with AUC>0.75 (λHU VP after nCRT, the change rate of NIC AP and NIC VP) was 0.869, with 80.0% sensitivity and 84.4% specificity. Conclusion:The quantitative parameters derived from spectral CT may provide new markers for evaluating the response to nCRT treatment in patients with LARC. The multi-parameter combined model can improve diagnostic efficacy.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Purpose: Knowing the distinction between benign and borderline/malignant phyllodes tumors (PTs) can help in the surgical treatment course. Herein, we investigated the value of magnetic resonance imaging-based texture analysis (MRI-TA) in differentiating between benign and borderline/malignant PTs. Methods: Forty-three women with 44 histologically proven PTs underwent breast MRI before surgery and were classified into benign (n = 26) and borderline/malignant groups (n = 18 [15 borderline, 3 malignant]). Clinical and routine MRI parameters (CRMP) and MRI-TA were used to distinguish benign from borderline/malignant PT. In total, 298 texture parameters were extracted from fat-suppression (FS) T2-weighted, FS unenhanced T1-weighted, and FS first-enhanced T1-weighted sequences. To evaluate the diagnostic performance, receiver operating characteristic curve analysis was performed for the K-nearest neighbor classifier trained with significantly different parameters of CRMP, MRI sequence-based TA, and the combination strategy. Results: Compared with benign PTs, borderline/malignant ones presented a higher local recurrence (p = 0.045); larger size (p < 0.001); different time-intensity curve pattern (p = 0.010); and higher frequency of strong lobulation (p = 0.024), septation enhancement (p = 0.048), cystic component (p = 0.023), and irregular cystic wall (p = 0.045). TA of FS T2-weighted images (0.86) showed a significantly higher area under the curve (AUC) than that of FS unenhanced T1-weighted (0.65, p = 0.010) or first-enhanced phase (0.72, p = 0.049) images. The texture parameters of FS T2-weighted sequences tended to have a higher AUC than CRMP (0.79, p = 0.404). Additionally, the combination strategy exhibited a similar AUC (0.89, p = 0.622) in comparison with the texture parameters of FS T2-weighted sequences. Conclusion MRI-TA demonstrated good predictive performance for breast PT pathological grading and could provide surgical planning guidance. Clinical data and routine MRI features were also valuable for grading PTs.

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.

Electrocardiogram (ECG) signals are easily disturbed by internal and external noise, and its morphological characteristics show significant variations for different patients. Even for the same patient, its characteristics are variable under different temporal and physical conditions. Therefore, ECG signal detection and recognition for the heart disease real-time monitoring and diagnosis are still difficult. Based on this, a wavelet self-adaptive threshold denoising combined with deep residual convolutional neural network algorithm was proposed for multiclass arrhythmias recognition. ECG signal filtering was implemented using wavelet adaptive threshold technology. A 20-layer convolutional neural network (CNN) containing multiple residual blocks, namely deep residual convolutional neural network (DR-CNN), was designed for recognition of five types of arrhythmia signals. The DR-CNN constructed by residual block local neural network units alleviated the difficulty of deep network convergence, the difficulty in tuning and so on. It also overcame the degradation problem of the traditional CNN when the network depth was increasing. Furthermore, the batch normalization of each convolution layer improved its convergence. Following the recommendations of the Association for the Advancements of Medical Instrumentation (AAMI), experimental results based on 94 091 2-lead heart beats from the MIT-BIH arrhythmia benchmark database demonstrated that our proposed method achieved the average detection accuracy of 99.034 9%, 99.498 0% and 99.334 7% for multiclass classification, ventricular ectopic beat (Veb) and supra-Veb (Sveb) recognition, respectively. Using the same platform and database, experimental results showed that under the comparable network complexity, our proposed method significantly improved the recognition accuracy, sensitivity and specificity compared to the traditional deep learning networks, such as deep Multilayer Perceptron (MLP), CNN, etc. The DR-CNN algorithm improves the accuracy of the arrhythmia intelligent diagnosis. If it is combined with wearable equipment, internet of things and wireless communication technology, the prevention, monitoring and diagnosis of heart disease can be extended to out-of-hospital scenarios, such as families and nursing homes. Therefore, it will improve the cure rate, and effectively save the medical resources.
Algorithms ; Arrhythmias, Cardiac ; diagnosis ; Electrocardiography ; Heart Rate ; Humans ; Neural Networks (Computer) ; Sensitivity and Specificity

We constructed the CAP2NC prokaryotic expression vector of HIV-1 NL4-3 strain and obtained relatively pure CAP2NC protein by optimizing its purification conditions to explore its in vitro self-assembly conditions. Primers were designed according to the CAP2NC DNA sequence of HIV-1 NL4-3 strain. The target gene was amplified by PCR and cloned into prokaryotic expression vector pTO-T7. Then the recombinant strain was transformed into Escherichia coli BL21 (DE3). IPTG induced protein expression, then the protein was purified by hydrophobic chromatography. SDS-PAGE and Western blotting were performed to analyze the target protein, and the biological activity of the antigen was identified through ELISA. The self-assembly of CAP2NC protein was analyzed by transmission electron microscopy and gel filtration chromatography. The protein had good reaction with the specific antibodies of p24 and formed different structures in various conditions. When 10% yeast RNA was added to the protein complex, the recombinant protein only formed into a tubular structure, which was similar to the self-assembled structure of the HIV-1 virus capsid. The results showed that the HIV-1 CAP2NC protein had in vitro self-assembly activity, and the RNA affected the structure of CAP2NC protein assembly. The protein can be used as a simple and effective molecular model to study its structure, and then it can provide a reference for the study of HIV immature virus particles.

Objective To explore the effect of heme oxygenase-1 (HO-1) on expressions of hypoxia inducing factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF)and regeneration of hepatic vascular plexus after orthotopic liver transplantation ischemia-reperfusion injury in rats.Methods Theexperimental study was conducted.According to the random number table,240 SD rats were divided into the 3 groups,80 rats in each group.Empty virus group:rats were transfected with the empty virus.Induced group:rats were transfected with HO-1 overexpression adenovirus.Inhibited group:rats were transfected with HO-1 RNAi adenovirus.Rats were made pairs (1 ∶ 1) and established rat liver transplantation model according to two cuffs method.Rats with less weight and with heavier weight were respectively chosen as donor rats and recipient rats,and then recieved tail intravenous injection of adenovirus at 24 hours before operation.(1) Detection of transfection efficiency of adenovirus before operation:HO-1 expression of liver tissue of rats in each group was detected by Western blot at 12 and 24 hours after injection of adenovirus.(2) Liver function test of recipient rats after liver transplantation:liver functions of recipient rats [alanine transaminase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),gamma-glutamyl transferase (GGT)] were detected at l,3,7 and 14 days postoperatively.(3) Pathological histology of liver tissue and injury scores of recipient rats in the 3 groups after liver transplantation:paraffin sections of recipient rats in the 3 groups at postoperative 1 and 14 days were stained by HE staining and observed by light microscope,and were evaluated by Suzuki damage score standard.(4) Relative expressions of HIF-1α,VEGF and HO-1 in liver tissue of recipient rats were detected by Western blot.(5) Von Willebrand factor (vWF) in liver tissue of recipient rats at 14 days postoperatively was detected by immunofluorescence staining and small vessels were counted.Measurement data with normal distribution were represented as x ±s.Comparison between groups was analyzed by the independent-sample t test,comparison among groups was done using one-way ANOVA,and pairwise comparison was analyzed by the LSD test.Results (1) Detection of transfection efficiency of adenovirus before operation:the relative expression of HO-1 of liver tissue of rats at 12 and 24 hours preoperatively after injection of adenovirus was 1.08±0.16 and 1.08±0.26 in the empty virus group,1.18±0.21 and 1.39±0.19 in the induced group,0.87±0.26 and 0.57±0.12 in the inhibited group,respectively,with statistically significant differences in different time points (F =4.232,36.513,P＜ 0.05).(2) Liver function test of recipient rats after liver transplantation:level of ALT at 3 days postoperatively in the empty virus group,induced group and inhibited group was (504±67)U/L,(438±47)U/L and (490±39)U/L,with a statistically significant difference (F=3.517,P＜0.05).Levels of ALT,AST and ALP at 7 days posto-peratively were (443±49) U/L,(430± 34) U/L,(455± 38) U/L in the empty virus group and (382± 49) U/L,(372±50) U/L,(394±25) U/L in the induced group and (493±44) U/L,(455±62) U/L,(470±72) U/L in the inhibited group,respectively,with statistically significant differences (F =10.950,5.667,5.398,P＜0.05).Levels of ALT,AST,ALP and GGT at 14 days postoperatively were (394±46)U/L,(361 ±68)U/L,(417 ±17)U/L,(4.5±1.1)U/L in the empty virus group and (283±47) U/L,(288±60) U/L,(332±46) U/L,(2.5±0.5) U/L in the induced group and (446± 43) U/L,(422± 51) U/L,(423± 63) U/L,(4.3 ± 1.3) U/L in the inhibited group,respectively,with statistically significant differences (F=26.906,9.924,8.013,9.279,P＜ 0.05).(3) Pathological histology of liver tissue and injury scores of recipient rats in the 3 groups after liver transplantation:liver cell swelling,loose cytoplasm and a varying quantity of inflammatory cell infiltration in the portal regions in the liver tissue of 3 groups were observed at 1 day postoperatively.A few inflammatory cell infiltrations in the portal regions,basically normal liver cell arrangement and a slightly swelling of liver cell were found in the empty virus group at 14 days postoperatively.Reduced liver cell swelling and basically normal structure of liver lobule were observed in the induced group.There were small patchy or focal necrosis of liver cell,masses of inflammatory cell infiltration in the portal regions and damage of bile duct in the inhibited group.Suzuki score at 1 day postoperatively in the empty virus group,induced group and inhibited group were respectively 6.7± 1.7,6.1 ± 1.2 and 7.6± 1.3,with no statistically significant difference (F=2.257,P＞0.05).Suzuki score at 14day postoperatively in the empty virus group,induced group and inhibited group were respectively 4.0±0.8,2.9± 0.8 and 5.1± 1.4,with a statistically significant difference (F=9.776,P＜0.05).(4) Western blot results:the relative expressions of HIF-1α and VEGF (43 KD) in liver tissue of recipient rats at 1 day postoperatively were 0.21±0.10,0.30±0.12 in the empty virus group and 0.23±0.09,0.34±0.14 in the induced group and 0.17± 0.06,0.29±0.11 in the inhibited group,respectively,with no statistically significant difference (F =0.902,0.410,P＞0.05).The relative expressions of VEGF (24 KD) and HO-1 in liver tissue of recipient rats at 1 day postoperatively were 1.21 ±0.25,0.55±0.12 in the empty virus group and 2.13±0.40,0.72±0.12 in the induced group and 0.91±0.22,0.26±0.07 in the inhibited group,respectively,with statistically significant differences (F=35.158,39.082,P ＜ 0.05).The relative expressions of HIF-1α,VEGF (43 KD),VEGF (24 KD) and HO-1 in liver tissue of recipient rats at 7 days postoperatively were 0.49±0.22,0.46±0.13,0.98± 0.37,0.98±0.37 in the empty virus group and 0.83±0.26,0.63±0.19,1.60±0.33,1.49±0.46 in the induced group and 0.24±0.09,0.30±0.12,0.64±0.18,0.75±0.26 in the inhibited group,respectively,with statistically significant differences (F=16.853,10.021,20.756,8.156,P＜0.05).(5) Immunofluorescence staining results:number of small vessels at 14 days postoperatively in the empty virus group,induced group and inhibited group was respectively 7.9±2.0,10.6± 1.9 and 7.6 ± 1.9,with a statistically significant difference (F=5.921,P＜0.05).Conclusion HO-1 could promote expressions of HIF-1α and VEGF in liver tissue after liver transplantation ischemia-reperfusion injury and regeneration of intrahepatic vascular plexus,and it also alleviate bile duct ischemia-reperfusion injury after liver transplantation.

AIM To establish the quality standard for Tibeten medicine Ershiwuwei Feibing Pills [Inula racemosa Hook.f.,Swertia bimaculata (Sieb.et Zucc.) Hook.Thors.ex Clarke,Phyllanthus emblica Linn.,Terminalia billerica (Gaertn.) Roxb.,etc.].METHODS TLC was applied to the qualitative identification of L racemosa,S.bimaculata,P.emblica and T.billerica,and HPLC was adopted in the quantitative determination of alantolactone,oleanolic acid,gallic acid and hydroxysafflor yellow A.RESULTS The TLC spots were clear without negative interference.Alantolactone,oleanolic acid,gallic acid and hydroxysafflor yellow A showed good linear relationships within the ranges of 4.324-216.2 μg/mL (r =0.999 9),32.222-1 611.1 μg/mL (r =0.999 9),4.072-203.6 μg/mL (r =0.999 9) and 4.266-213.3 μg/mL (r =0.999 9),whose average recoveries (RSDs) were 100.6％ (0.93％),100.3％ (2.1％),101.5％ (3.0％) and 100.1％ (1.8％),respectively.CONCLUSION This simple method can be used for the rapid quality control of Ershiwuwei Feibing Pills.