Vicious Cycle-Breaking Lipid Nanoparticles Remodeling Multicellular Crosstalk to Reverse Liver Fibrosis.

During liver fibrogenesis, the reciprocal crosstalk among capillarized liver sinusoidal endothelial cells (LSECs), activated hepatic stellate cells (HSCs), and dysfunctional hepatocytes constructs a self-amplifying vicious cycle, greatly exacerbating the disease condition and weakening therapeutic effect. Limited by the malignant cellular interactions, the previous single-cell centric treatment approaches show unsatisfactory efficacy and fail to meet clinical demand. Herein, a vicious cycle-breaking strategy is proposed to target and repair pathological cells separately to terminate the malignant progression of liver fibrosis. Chondroitin sulfate-modified and vismodegib-loaded nanoparticles (CS-NPs/VDG) are designed to efficiently normalize the fenestrae phenotype of LSECs and restore HSCs to quiescent state by inhibiting Hedgehog signaling pathway. In addition, glycyrrhetinic acid-modified and silybin-loaded nanoparticles (GA-NPs/SIB) are prepared to restore hepatocytes function by relieving oxidative stress. The results show successful interruption of vicious cycle as well as distinct fibrosis resolution in two animal models through multiregulation of the pathological cells. This work not only highlights the significance of modulating cellular crosstalk but also provides a promising avenue for developing antifibrotic regimens.

How should preoperative examinations be chosen for infants with a ventricular septal defect: transthoracic echocardiography, cardiac CTA, or a combination of these two technologies?

OBJECTIVE: To evaluate the accuracy of transthoracic echocardiography (TTE) and cardiac computed tomography angiography (CTA) in detecting the size and location of ventricular septal defects (VSD) in infants. METHODS: Data from 258 infants diagnosed with VSD between January 2020 and December 2022 were retrospectively analyzed. All infants underwent both TTE and cardiac CTA. The accuracy of these imaging modalities was assessed by comparing their findings with intraoperative observations of VSD size and location. RESULTS: Intraoperatively, the average VSD size was 6.1 ± 2.5 mm. The defects were classified as committed VSD (Type 1) in 45 patients, noncommitted VSD (Type 2) in 198 patients, inlet VSD (Type 3) in 12 patients, and muscular VSD (Type 4) in 3 patients. Echocardiography estimated the average VSD size at 5.6 ± 2.7 mm, with 42 patients identified as Type 1, 203 as Type 2, 10 as Type 3, and 3 as Type 4. Cardiac CTA estimated the average size at 5.9 ± 3.2 mm, with 48 patients identified as Type 1, 196 as Type 2, 11 as Type 3, and 3 as Type 4. The accuracy rates of TTE and cardiac CTA in diagnosing VSD location were 98.1% and 98.8%, respectively. A survey of surgeons indicated that 80% believe both TTE and cardiac CTA are essential preoperative evaluations. CONCLUSIONS: TTE accurately diagnoses the size and location of VSD, while cardiac CTA serves as a valuable complementary method to TTE. Most surgeons advocate for the combined use of these examinations for preoperative assessment.

Novel biotin-linked amphiphilic calix[4]arene-based supramolecular micelles as doxorubicin carriers for boosted anticancer activity.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

[Simultaneous determination of 36 mycotoxins in fruits by QuEChERS coupled with ultra performance liquid chromatography-tandem mass spectrometry].

Mycotoxins are secondary metabolites produced by toxigenic fungi under specific environmental conditions. Fruits, owing to their high moisture content, rich nutrition, and improper harvest or storage conditions, are highly susceptible to various mycotoxins, such as ochratoxin A (OTA), zearalenone (ZEN), patulin (PAT), Alternaria toxins, etc. These mycotoxins can cause acute and chronic toxic effects (teratogenicity, mutagenicity, and carcinogenicity, etc) in animals and humans. Given the high toxicity and wide prevalence of mycotoxins, establishing an efficient analytical method to detect multiple mycotoxins simultaneously in different types of fruits is of great importance. Conventional mycotoxin detection methods rely on high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). However, fruit sample matrices contain large amounts of pigments, cellulose, and minerals, all of which dramatically impede the detection of trace mycotoxins in fruits. Therefore, the efficient enrichment and purification of multiple mycotoxins in fruit samples is crucial before instrumental analysis. In this study, a reliable method based on a QuEChERs sample preparation approach coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to determine 36 mycotoxins in fruits. In the optimal extraction method, 2.0 g of a sample was extracted with 10 mL of acetic acid-acetonitrile-water (1∶79∶20, v/v/v) in a 50 mL centrifuge tube, vortexed for 30 s, and ultrasonicated for 40 min. The mixture was then salted out with 2.0 g of anhydrous MgSO4 and 0.5 g of NaCl and centrifuged for 5 min. Next, 6 mL of the supernatant was purified using 85 mg of octadecylsilane-bonded silica gel (C18) and 15 mg of N-propylethylenediamine (PSA). After vigorous shaking and centrifugation, the supernatant was collected and dried with nitrogen at 40 ℃. Finally, the residues were redissolved in 1 mL of 5 mmol/L ammonium acetate aqueous solution-acetonitrile (50∶50, v/v) and passed through a 0.22 µm nylon filter before analysis. The mycotoxins were separated on a Waters XBridge BEH C18 column using a binary gradient mixture of ammonium acetate aqueous solution and methanol. The injection volume was 3 µL. The mycotoxins were analyzed in multiple reaction monitoring (MRM) mode under both positive and negative electrospray ionization. Quantitative analysis was performed using an external standard method with matrix-matched calibration curves. Under optimal conditions, good linear relationships were obtained in the respective linear ranges, with correlation coefficients (R2) no less than 0.990. The limits of detection (LODs) and quantification (LOQs) were 0.02-5 and 0.1-10 µg/kg, respectively. The recoveries of the 36 mycotoxins in fruits ranged from 77.0% to 118.9% at low, medium, and high spiked levels, with intra- and inter-day precisions in the range of 1.3%-14.9% and 0.2%-17.3%, respectively. The validated approach was employed to investigate mycotoxin contamination in actual fruit samples, including strawberry, grape, pear, and peach (15 samples of each type). Eleven mycotoxins, namely, altenuene (ALT), altenusin (ALS), alternariol-methyl ether (AME), tenuazonic acid (TeA), tentoxin (Ten), OTA, beauvericin (BEA), PAT, zearalanone (ZAN), T-2 toxin (T2), and mycophenolic acid (MPA), were found in the samples; three samples were contaminated with multiple mycotoxins. The incidence rates of mycotoxins in strawberry, grape, pear, and peach were 27%, 40%, 40%, and 33%, respectively. In particular, Alternaria toxins were the most frequently found mycotoxins in these fruits, with an incidence of 15%. The proposed method is simple, rapid, accurate, sensitive, reproducible, and stable; thus, it is suitable for the simultaneous detection of the 36 mycotoxins in different fruits.

Using Revolution™ CT Angiography to Assess Complex Coarctation of the Aorta in Infants and Its Association with a Prolonged Postoperative Cardiac ICU Stay.

OBJECTIVE: To investigate the accuracy of aortic dimensions measured by Revolution™ computed tomography (CT) in infants with complex coarctation of the aorta (CoA) and to further analyze the utility of the degree of CoA in predicting the risk of prolonged postoperative cardiac intensive care unit stay. METHODS: A total of 30 infants with complex CoA who underwent surgical correction from January 2020 to July 2022 were retrospectively enrolled. General demographic data, preoperative imaging, and perioperative outcomes were collected. Univariate and multivariate analyses were performed to investigate predictors of prolonged postoperative cardiac intensive care unit stay, and the reliability of the CT measurements was assessed by the intraclass correlation coefficient. RESULTS: All infants were divided into a mild or severe CoA group. The duration of mechanical ventilation and cardiac intensive care unit stay in the mild CoA group were significantly lower than those in the severe CoA group. After multivariate analysis, we found that the degree of CoA and age at surgery were significant predictors of prolonged postoperative cardiac intensive care unit stay. The intraclass correlation coefficient between CT measurements and intraoperative measurements was between 0.937 and 0.975, and the measurement results had good reliability. CONCLUSION: CT angiography can provide a comprehensive and accurate preoperative evaluation of aortic dimensions measured in infants with complex CoA. The degree of CoA is an independent risk factor for prolonged postoperative cardiac intensive care unit stay in infants with complex CoA.

Using Revolution™ CT Angiography to Assess Complex Coarctation of the Aorta in Infants and Its Association with a Prolonged Postoperative Cardiac ICU Stay

ABSTRACT Objective: To investigate the accuracy of aortic dimensions measured by Revolution™ computed tomography (CT) in infants with complex coarctation of the aorta (CoA) and to further analyze the utility of the degree of CoA in predicting the risk of prolonged postoperative cardiac intensive care unit stay. Methods: A total of 30 infants with complex CoA who underwent surgical correction from January 2020 to July 2022 were retrospectively enrolled. General demographic data, preoperative imaging, and perioperative outcomes were collected. Univariate and multivariate analyses were performed to investigate predictors of prolonged postoperative cardiac intensive care unit stay, and the reliability of the CT measurements was assessed by the intraclass correlation coefficient. Results: All infants were divided into a mild or severe CoA group. The duration of mechanical ventilation and cardiac intensive care unit stay in the mild CoA group were significantly lower than those in the severe CoA group. After multivariate analysis, we found that the degree of CoA and age at surgery were significant predictors of prolonged postoperative cardiac intensive care unit stay. The intraclass correlation coefficient between CT measurements and intraoperative measurements was between 0.937 and 0.975, and the measurement results had good reliability. Conclusion: CT angiography can provide a comprehensive and accurate preoperative evaluation of aortic dimensions measured in infants with complex CoA. The degree of CoA is an independent risk factor for prolonged postoperative cardiac intensive care unit stay in infants with complex CoA.

Accuracy and image quality of wide-detector revolution CT angiography combined with prospective ECG-triggered CT angiography in the diagnosis of congenital aortic arch anomalies in Chinese children.

Objective: To explore the accuracy and image quality of wide-detector revolution CT angiography combined with prospective ECG-triggered CT angiography in the diagnosis of congenital aortic arch anomalies in Chinese children. Methods: From January 2020 to July 2022, the clinical data of 57 children with congenital aortic arch anomalies confirmed by surgery were collected. All patients underwent CT angiography (CTA) with Revolution CT and transthoracic echocardiography (TTE) before the operation. The accuracy of CTA and TTE in the diagnosis of aortic arch anomalies was compared with the surgical results. Result: The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CTA and TTE for congenital aortic arch anomalies (including intracardiac and extracardiac structural abnormalities) were 92.2% and 85.5%, 99.4%, and 99.1%, 97.4% and 95.6%, 98.1% and 96.9%, and 97.2% and 95.2%, respectively. Regarding extracardiac structural malformations, the sensitivity of CTA was 100%, whereas that of TTE was 78.6% (P < 0.001). Regarding intracardiac structural malformations, the sensitivity of CTA was 84.5%, whereas that of TTE was 92.5% (P < 0.001). Regarding satisfaction with the images in aortic arch anomalies, surgeons noted that the CTA images were more useful for diagnosis and operation planning compared with TTE. Conclusion: Wide-detector revolution CT angiography combined with prospective ECG triggering can be routinely used to assess congenital aortic arch anomalies, providing adequate image quality and high diagnostic accuracy. However, limitations in the identification of intracardiac structural abnormalities are noted.

Computed tomography angiography assessment of the degree of simple coarctation of the aorta and its relationship with surgical outcome: A retrospective analysis.

Objective: To investigate the correlation between the degree of aortic coarctation and surgical prognosis in infants with simple coarctation of the aorta (CoA) using computed tomography angiography (CTA). Methods: This study was a retrospective study. Twenty-seven infants with simple CoA who underwent surgical correction from January 2020 to June 2022 were enrolled. Aortic diameters were measured at five different levels and normalized to Z scores based on the square root of body surface area. The relevant data were collected and analyzed, and the predictors associated with surgical outcome were determined. Results: Patients were divided into the mild CoA group and the severe CoA group according to the severity of coarctation. The mechanical ventilation duration and the length of ICU stay in the mild CoA group were significantly lower than those in the severe CoA group. Multiple linear regression analyses revealed that the degree of aortic coarctation was a significant risk factor for a prolonged postoperative ICU stay. In addition, gestational age and age at operation were risk factors for a prolonged postoperative ICU stay. Correlation analysis showed that the degree of aortic coarctation correlated with the Z scores of the ascending aorta and postcoarctation aorta. Conclusion: The degree of the CoA is an important predictor of surgical outcomes in infants with simple CoA and was significantly correlated with the ascending aorta and postcoarctation aorta Z scores. Therefore, preoperative CTA should be routinely performed to assess the degree of aortic coarctation and better identify risk factors.

Evaluation of the aorta in infants with simple or complex coarctation of the aorta using CT angiography.

Objective: To assess aortic dilatation and determine its related factors in infants with coarctation of the aorta (CoA) by using computed tomography angiography (CTA). Methods: The clinical data of 55 infantile patients with CoA diagnosed by CTA were analyzed retrospectively. Aortic diameters were measured at six different levels and standardized as Z scores based on the square root of body surface area. The results of simple and complex CoA were compared. Univariate and multivariate logistic regression were used to analyze the effects of sex, age, hypertension, degree of coarctation, CoA type, bicuspid aortic valve (BAV), and other factors related to aortic dilatation. Results: In total, 52 infant patients with CoA were analyzed, including 22 cases of simple CoA and 30 cases of complex CoA. The ascending aorta of the infants in the simple CoA group and the complex CoA group were dilated to different degrees, but the difference was not statistically significant (50.00% vs. 73.33%, P = 0.084, and 2.05 ± 0.40 vs. 2.22 ± 0.43 P = 0.143). The infants in the complex CoA group had more aortic arch hypoplasia than those in the simple CoA group (33.33% vs. 9.09%, P = 0.042). Compared to the ventricular septal defect (VSD) group, the Z score of the ascending aorta in the CoA group was significantly higher than that in the VSD group (P = 0.023 and P = 0.000). A logistic retrospective analysis found that an increased degree of coarctation (CDR value) was an independent predictor of ascending aortic dilatation (adjusted OR = 0.002; P = 0.034). Conclusion: Infants with simple or complex CoA are at risk of ascending aortic dilatation, and the factors of ascending aortic dilatation depend on the degree of coarctation. The risk of aortic dilatation in infants with CoA can be identified by CTA.

CCNI2 plays a promoting role in the progression of colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies and most of the patients diagnosed with advanced CRC have unsatisfactory treatment effect and poor prognosis. The purpose of this study was to investigate the effect of CCNI2 on the development of CRC. In this sutdy, immunohistochemical staining was used to detect CCNI2 expression levels in clinical samples, meanwhile, the Kaplan-Meier survival analysis was conducted. Celigo cell counting assay was used for screening shCCNI2s. QPCR and WB were performed to verify knockdown efficiency of CCNI2. Cell proliferation, colony formation, cell cycle, apoptosis, and mechanism investigation of CCNI2 knockdown were investigated by MTT assay, colony formation assay, fluorescence-activated cell sorting, and human apoptosis antibody array, respectively. Otherwise, the mouse model of CCNI2 knockdown was also constructed. The results of immunohistochemical staining and qPCR indicated that CCNI2 had a high expression level in the CRC tissues and cell lines. Kaplan-Meier survival analysis manifested that the high expression of CCNI2 suggested poor prognosis. The expression of CCNI2 was significantly reduced by CCNI2-siRNAs, and the downregulated expression level of CCNI2 inhibited CRC cell proliferation and colony formation, arrested cell cycle in G2 phase, as well as promoted cell apoptosis. The various indexes of solid tumor in mice models indicated that CCNI2 knockdown could suppress the growth of CRC tumor. Based on the comprehensive analysis of the above results, CCNI2 was contributed to the progression of CRC and could serve as a prognostic marker for CRC.

An investigation on health risk behaviors among high school students in Jiangxi province / 中国学校卫生

Objective@#To determine health risk behaviors related to accidental injury of adolescent in Jiangxi province,and to provide a peference for taking targeted measures to prevent the occurence of adolescent’s risk behaviors. @*Methods@#By using the cluster stratified sampling, students of grade one and grade two from 10 classes in 5 middle schools in Nanchang city and from 1 middle school in Wuyuan county were selected. Health risk behaviors were investigated through questionnaire survey and were compared within the two areas.@*Results@#Regarding to safety, the rates of never or rarely wearing a helmet when riding a bicycle during the past 12 months, never or rarely wearing a seat belt, text or Email while driving a vehicle and in a physical fight were very high. In Wuyuan county, 35.2% of the students have ever tried cigarette smoking, 51.5% of the students have had at least one drink of alcohol, 4.0% of the students have ever had sexual intercourse, 32.7% of the students describe their weight as slightly or very overweight, 49.1% of the students trying to lose weight. After standardized, the rate of health risk behaviors in Nanchang city was higher than that in Wuyuan county.@*Conclusion@#here are more healthrisk behaviors found among middle school students in Nanchang than in Wuyuan county.The targeted measures should be taken to develop healthy behavior habits of the students to effectively reduce its occurence.

miR218-5p regulates the proliferation of gastric cancer cells by targeting TFF1 in an Erk1/2-dependent manner.

Trefoil factor 1 (TFF1), a member of the trefoil peptide family, is not only associated with mucosal protection and restoration but is also correlated with tumorigenesis of the gastrointestinal tract. In an early study, we performed sequence analysis and identified one potential miR423-5p binding site within the 3'-untranslated region of TFF1 using microRNA target prediction tools. In the current study, we demonstrated that the coding DNA region within TFF1 is also a candidate for miR218-5p targeting. We used real-time PCR and in situ hybridization to analyze the correlation between miR218-5p and TFF1 expression in tumor lesions and paracancerous tissue in gastric cancer (GC) samples. Additionally, endogenous and exogenous TFF1 were suppressed by miR218-5p in gastric cancer cells and influenced the progression of GC in an Erk1/2-dependent manner. Targeting miR218-5p may provide a novel strategy for the treatment of GC.

ECHS1 acts as a novel HBsAg-binding protein enhancing apoptosis through the mitochondrial pathway in HepG2 cells.

We aimed to confirm the role of ECHS1 as a binding protein of HBsAg (HBs) and investigate its function during the development of hepatocellular carcinoma (HCC). Our results show that both exogenous and endogenous ECHS1 proteins bind to HBs and co-localize in the cytoplasm in vitro. The coexistence of HBs and ECHS1 enhances HepG2 cell apoptosis, affects ECHS1 localization in the mitochondria and induces apoptosis by decreasing the mitochondrial membrane potential (MMP). These findings suggest that ECHS1 may be applied as a potential therapeutic target during the treatment of HBV-related hepatitis or HCC.

TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells.

Increasing evidence indicates that in gastric epithelial cells, induction of TFF3 by hypoxia is mediated by HIF-1. Since VEGF is one of the most important angiogenic factors on cancer progression, we have started to investigate the possible link among HIF-1α, VEGF, and TFF3 in gastric cancer cells. We induced the hypoxic condition in SGC-7901cells using hypoxia-mimetic agent of CoCI2. SGC7901 cells were transfected with pcPUR + U6 plasmid carrying RNAi targeted to human TFF3 and selected puromycin-resistant pools to establish the stable knockdown of TFF3 cells. Our results showed the induction of HIF-1a via hypoxia and consequences of increased expressions of the TFF3 and VEGF in gastric cancer SGC-7901 cells. Overexpression of TFF3 upregulated the mRNA expressions of VEGF and HIF-1a induced by hypoxia, and stable knockdown of TFF3 impaired the mRNA upregulations of VEGF and HIF-1a induced by hypoxia. Furthermore, knockdown of TFF3 reduced the VEGF protein secretion: as VEGF secretion was increased time dependent manner in response to the hypoxia induction in TFF3-WT cells; however, VEGF production was significantly decreased in TFF3-KD cells (621 ± 89 vs. 264 ± 73 at 6 h and 969 ± 97 vs. 508 ± 69 at 12 h, P < 0.05). Our data demonstrated the TFF3 mediated regulation of VEGF expression induced by hypoxia, and implicated that TFF3 might be applied as a potential anti-angiogenic target for treatment of gastric cancer.