Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.

Crosstalk between autophagy and inflammasomes in ricin-induced inflammatory injury.

Ricin (ricin toxin, RT) has the potential to cause damage to multiple organs and systems. Currently, there are no existing antidotes, vaccinations, or effective therapies to prevent or treat RT intoxication. Apart from halting protein synthesis, RT also induces oxidative stress, inflammation and autophagy. To explore the mechanisms of RT-induced inflammatory injury and specific targets of prevention and treatment for RT poisoning, we characterized the role of cross-talk between autophagy and NLRP3 inflammasome in RT-induced damage and elucidated the underlying mechanisms. We showed that RT-induced inflammation was attributed to activation of the TLR4/MyD88/NLRP3 signaling and ROS production, evidenced by increased ASC speck formation and attenuated TXNIP/TRX-1 interaction, as well as pre-treatment with MCC950, MyD88 knockdown and NAC significantly reduced IL-1ß, IL-6 and TNF-α mRNA expression. In addition, autophagy is also enhanced in RT-triggered MLE-12 cells. RT elevated the levels of ATG5, p62 and Beclin1 protein, provoked the accumulation of LC3 puncta detected by immunofluorescence staining. Treatment with rapamycin (Rapa) reversed the RT-caused TLR4/MyD88/NLRP3 signaling activation, ASC specks formation as well as the levels of IL-1ß, IL-6 and TNF-α mRNA. In conclusion, RT promoted NLRP3 inflammasome activation and autophgay. Inflammation induced by RT was attenuated by autophagy activation, which suppressed the NLRP3 inflammasome. These findings suggest Rapa as a potential therapeutic drug for the treatment of RT-induced inflammation-related diseases.

Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71.

Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.

AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via BadSer136 phosphorylation.

Epithelial disruption is the initiation of most infectious disease. Regulation of epithelium apoptosis may play a key role in balance the survival competition between resident bacteria and host cells. The role of the mTOR/p70S6K pathway in preventing apoptosis of human gingival epithelial cells (hGECs) infected with Porphyromonas gingivalis (Pg) was investigated in order to further understand the survival strategy of the epithelial cells in during Pg infecting. hGECs was challenged with Pg for 4, 12, and 24 h. Additionally, hGECs was pretreated with LY294002 (PI3K signaling inhibitor) or Compound C (AMPK inhibitor) for 12 h and exposed them to Pg for 24 h. Subsequently, apoptosis was detected using flow cytometry, and expression and activity of Bcl-2, Bad, Bax, PI3K, AKT, AMPK, mTOR, and p70S6K proteins were analyzed using western blotting. Pg-infecting did not increase apoptosis of hGECs; but the expression ratio of Bad to Bcl-2 was increased after infecting. In contrast, BadSer136 phosphorylation was promoted, accompanied by a significant reduction of mTOR/p70S6K and PI3K/AKT signaling, along with the upregulation of AMPKThr172 signaling. Morrover, the PI3K inhibitor LY294002 promoted Pg-mediated reduction of mTOR/p70S6K expression, and the increase of AMPK signaling and BadSer136 phosphorylation rate, eventually decreasing apoptosis. While Compound C inhibited Pg-mediated activation of AMPK and downregulation of mTOR/p70S6K signaling, significantly reduced the BadSer136 phosphorylation rate, thereby increasing apoptosis. Thus, hGECs prevent apoptosis via an inherent cellular-homeostasis, pro-survival mechanism during Pg infection, the AMPK/mTOR/p70S6K pathway helps prevent apoptosis in hGECs infected with Pg by regulating BadSer136 phosphorylation.

Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, which has yet no curable medication. Neuroinflammation and mitochondrial dysfunction are tightly linked to DPN pathology. G-protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic ß-cells, but also in spinal dorsal horn and dorsal root ganglion (DRG) neurons, regulating neuropathic pain. We previously have reported that vincamine (Vin), a monoterpenoid indole alkaloid extracted from Madagascar periwinkle, is a GPR40 agonist. In this study, we evaluated the therapeutic potential of Vin in ameliorating the DPN-like pathology in diabetic mice. Both STZ-induced type 1 (T1DM) and db/db type 2 diabetic (T2DM) mice were used to establish late-stage DPN model (DPN mice), which were administered Vin (30 mg·kg-1·d-1, i.p.) for 4 weeks. We showed that Vin administration did not lower blood glucose levels, but significantly ameliorated neurological dysfunctions in DPN mice. Vin administration improved the blood flow velocities and blood perfusion areas of foot pads and sciatic nerve tissues in DPN mice. We demonstrated that Vin administration protected against sciatic nerve myelin sheath injury and ameliorated foot skin intraepidermal nerve fiber (IENF) density impairment in DPN mice. Moreover, Vin suppressed NLRP3 inflammasome activation through either ß-Arrestin2 or ß-Arrestin2/IκBα/NF-κB signaling, improved mitochondrial dysfunction through CaMKKß/AMPK/SIRT1/PGC-1α signaling and alleviated oxidative stress through Nrf2 signaling in the sciatic nerve tissues of DPN mice and LPS/ATP-treated RSC96 cells. All the above-mentioned beneficial effects of Vin were abolished by GPR40-specific knockdown in dorsal root ganglia and sciatic nerve tissues. Together, these results support that pharmacological activation of GPR40 as a promising therapeutic strategy for DPN and highlight the potential of Vin in the treatment of this disease.

Risk prediction model for long-term atelectasis in children with pneumonia.

BACKGROUND: This study aimed to develop a risk prediction model for long-term atelectasis in children with pneumonia. METHODS: A retrospective study of 532 children with atelectasis was performed at the Children's Hospital of Chongqing Medical University from February 2017 to March 2020. The predictive variables were screened by LASSO regression analysis and the nomogram was drawn by R software. The area under the Receiver Operating Characteristic (ROC) curve, calibration chart and decision curve were used to evaluate the predictive accuracy and clinical utility. 1000 Bootstrap resampling was used for internal verification. RESULTS: Multivariate logistic regression analysis showed that clinical course before bronchoscopy, length of stay, bronchial mucus plug formation, age were independent risk factors for long-term atelectasis in children. The area under the ROC curve of nomogram was 0.857(95% CI = 0.8136 ~ 0.9006) in training set and 0.849(95% CI = 0.7848-0.9132) in the testing set. The calibration curve demonstrated that the nomogram was well-fitted, and decision curve analysis (DCA) showed that the nomogram had good clinical utility. CONCLUSIONS: The model based on the risk factors of long-term atelectasis in children with pneumonia has good predictive accuracy and consistency, which can provide a certain reference value for clinical prevention and treatment of long-term atelectasis in children.

Analysis of Volatile Compounds and Flavor Fingerprint Using Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) on Crassostrea gigas with Different Ploidy and Gender.

In this study, GC-IMS was used to analyze the volatile component and flavor profiles of Crassostrea gigas individuals of different ploidy and gender. Principal component analysis was used to explore overall differences in flavor profiles, and a total of 54 volatile compounds were identified. The total volatile flavor contents in the edible parts of tetraploid oysters were significantly higher than in diploid and triploid oysters. The concentrations of ethyl (E)-2-butenoate and 1-penten-3-ol were significantly higher in triploid oysters than in diploid and tetraploid oysters. In addition, the volatile compounds propanoic acid, ethyl propanoate, 1-butanol, butanal, and 2-ethyl furan were significantly higher in females than in males. The volatile compounds p-methyl anisole, 3-octanone, 3-octanone, and (E)-2-heptenal were present in higher levels in male than in female oysters. Overall, different ploidy and gender of oysters are connected with different sensory characteristics, providing new insights for understanding the flavor characteristics of oysters.

[Determination of three furfural compounds in coffee and coffee products by gas chromatography-tandem mass spectrometry with internal standard isotope].

OBJECTIVE: To establish a method for the determination of three furfural compounds in coffee and its products by gas chromatography-tandem mass spectrometry. METHODS: The samples were extracted with ethanol water(1∶2, V∶V) solution, ultrasonic with 10% Na_2CO_3 solution for 5 min, purified with 100 mg C_(18), 50 mg Srong Cation exchang(SCX), 150 mg anhydrous MgSO_4, separated by HP-INNOWAX capillary column(30 m×0.25 mm, 0.25 µm), detected by gas chromatography-tandem mass spectrometry, and quantified by isotope internal standard method. RESULTS: The correlation coefficients(r) of the three furfural compounds were all greater than 0.999, the limits of detection were 0.004-0.011 mg/kg, and the limits of quantitation were 0.013-0.031 mg/kg. The average recoveries were 86.0%-112% and the relative standard deviations were 4.1%-10.6%(n=6), at 3 supplemental levels in 3 different coffee substrates. Nine samples of coffee beans, instant coffee and coffee drinks were tested, and all three components to be tested were detected. CONCLUSION: The method is simple, rapid, sensitive, with good accuracy and precision. It is suitable for the determination of three furfural compounds in coffee and its products.

A chromosome-level genome of Semiothisa cinerearia provides insights into its genome evolution and control.

BACKGROUND: Semiothisa cinerearia belongs to Geometridae, which is one of the most species-rich families of lepidopteran insects. It is also one of the most economically significant pests of the Chinese scholar tree (Sophora japonica L.), which is an important urban greenbelt trees in China due to its high ornamental value. A genome assembly of S. cinerearia would facilitate study of the control and evolution of this species. RESULTS: We present a reference genome for S. cinerearia; the size of the genome was ~ 580.89 Mb, and it contained 31 chromosomes. Approximately 43.52% of the sequences in the genome were repeat sequences, and 21,377 protein-coding genes were predicted. Some important gene families involved in the detoxification of pesticides (P450) have expanded in S. cinerearia. Cytochrome P450 gene family members play key roles in mediating relationships between plants and insects, and they are important in plant secondary metabolite detoxification and host-plant selection. Using comparative analysis methods, we find positively selected gene, Sox15 and TipE, which may play important roles during the larval-pupal metamorphosis development of S. cinerearia. CONCLUSION: This assembly provides a new genomic resource that will aid future comparative genomic studies of Geometridae species and facilitate future evolutionary studies on the S. cinerearia.

Accuracy and Challenges in the Vesical Imaging-Reporting and Data System for Staging Bladder Cancer.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) scoring system has been widely used to stage bladder cancer (BCa) since 2018. PURPOSE: To describe the characteristics of cases with discordant T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) scores in patients with BCa and further verify the accuracy of the VI-RADS scoring system and the necessity of dynamic contrast-enhanced (DCE) sequence. STUDY TYPE: Retrospective. SUBJECTS: A total of 106 patients (include 16.5% female) with bladder cancer. SEQUENCE: T2WI (fast spin echo), DWI (echo planer imaging), and DCE (gradient echo). ASSESSMENT: Some cases are difficult to score according to the system, mainly when the T2WI (category 4) and DWI (category 2) sequence scores are discordant, termed the discordant group below. The complementary group will be termed concordant group. Each MRI sequence was reviewed respectively according to the 5-point VI-RADS scoring system by three observers. The diagnostic ability of sequences for evaluating muscle invasion by BCa was calculated using histopathology as the reference standards. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, DeLong test, intraclass correlation coefficient. A P value of 0.05 or less was considered statistically significant. RESULTS: Fourteen cases (13.2%) had discordant VI-RADS scoring system. In the discordant group, the area under the ROC curve (AUC) of DCE was 0.875, while the T2WI and DWI showed limited diagnostic performance (AUCs = 0.50). In the concordant group, there was no significant difference in diagnostic efficacy between the overall VI-RADS (AUC: 0.950) and the combination of T2WI and DWI (AUC: 0.946) (P = 0.56). Among all patients, the AUC of overall VIRADS was 0.939 with a 3 or greater cutoff value. DATA CONCLUSION: The DCE was crucial in the discordant group for evaluating muscle-invasiveness, while DCE may not be necessary for the concordant group. The VI-RADS scoring system performed with overall good diagnostic performance in evaluating muscle-invasiveness in BCa patients. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Evaluation of a fractional-order calculus diffusion model and bi-parametric VI-RADS for staging and grading bladder urothelial carcinoma.

OBJECTIVES: To evaluate the feasibility of high b-value diffusion-weighted imaging (DWI) for distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC) and low- from high-grade bladder urothelial carcinoma using a fractional-order calculus (FROC) model as well as a combination of FROC DWI and bi-parametric Vesical Imaging-Reporting and Data System (VI-RADS). METHODS: Fifty-eight participants with bladder urothelial carcinoma were included in this IRB-approved prospective study. Diffusion-weighted images, acquired with 16 b-values (0-3600 s/mm2), were analyzed using the FROC model. Three FROC parameters, D, ß, and µ, were used for delineating NMIBC from MIBC and for tumor grading. A receiver operating characteristic (ROC) analysis was performed based on the individual FROC parameters and their combinations, followed by comparisons with apparent diffusion coefficient (ADC) and bi-parametric VI-RADS based on T2-weighted images and DWI. RESULTS: D and µ were significantly lower in the MIBC group than in the NMIBC group (p = 0.001 for each), and D, ß, and µ all exhibited significantly lower values in the high- than in the low-grade tumors (p ≤ 0.011). The combination of D, ß, and µ produced the highest specificity (85%), accuracy (78%), and the area under the ROC curve (AUC, 0.782) for distinguishing NMIBC and MIBC, and the best sensitivity (89%), specificity (86%), accuracy (88%), and AUC (0.892) for tumor grading, all of which outperformed the ADC. The combination of FROC parameters with bi-parametric VI-RADS improved the AUC from 0.859 to 0.931. CONCLUSIONS: High b-value DWI with a FROC model is useful in distinguishing NMIBC from MIBC and grading bladder tumors. KEY POINTS: • Diffusion parameters derived from a FROC diffusion model may differentiate NMIBC from MIBC and low- from high-grade bladder urothelial carcinomas. • Under the condition of a moderate sample size, higher AUCs were achieved by the FROC parameters D (0.842) and µ (0.857) than ADC (0.804) for bladder tumor grading with p ≤ 0.046. • The combination of the three diffusion parameters from the FROC model can improve the specificity over ADC (85% versus 67%, p = 0.031) for distinguishing NMIBC and MIBC and enhance the performance of bi-parametric VI-RADS.

Detection of pulmonary tuberculosis in children using the Xpert MTB/RIF Ultra assay on sputum: a multicenter study.

Microbiological confirmation is rare in children with active tuberculosis; therefore, a more accurate test is needed to detect pulmonary tuberculosis in children. In this multicenter study, we evaluated the utility of the Xpert MTB/RIF Ultra (Ultra) on sputum, an assay recommended by the World Health Organization to test for childhood tuberculosis in high-burden settings. Children with symptoms suggestive of tuberculosis were enrolled at three hospitals in China and categorized as having active tuberculosis or nontuberculosis. The sensitivity and specificity of Ultra were 42.1% (48/114) and 99.0% (208/210), respectively. Using three MTB culture results as the reference, the sensitivity of Ultra in the subset of 38 children with culture-positive and 76 children with culture-negative was 68.4% (26/38) and 28.9% (22/76), respectively(p < 0.001). A single MTB culture combined with a single Ultra could detect 54 (54/114,47.4%) cases with active TB, while repeated MTB culture combined with a single Ultra detected 60 (60/114, 52.6%) cases with active TB(p = 0.427). Among 155 children (58 with TB and 97 with RTIs) simultaneously tested with the Ultra and Xpert MTB/RIF (Xpert), the sensitivity of the Xpert (24.1%, 14/58) was lower than that of the Ultra (41.4%, 24/58; p = 0.048). Eight children were found to have rifampin-resistant MTB strains. The Xpert MTB/RIF Ultra assay should be implemented to test for pulmonary tuberculosis in children to achieve higher confirmation rates.

WiFi Indoor Location Based on Area Segmentation.

Indoor positioning is the basic requirement of future positioning services, and high-precision, low-cost indoor positioning algorithms are the key technology to achieve this goal. Different from outdoor maps, indoor data has the characteristic of uneven distribution and close correlation. In areas with low data density, in order to achieve a high-precision positioning effect, the positioning time will be correspondingly longer, but this is not necessary. The instability of WiFi leads to the introduction of noise when collecting data, which reduces the overall performance of the positioning system, so denoising is very necessary. For the above problems, a positioning system using the DBSCAN algorithm to segment regions and realize regionalized positioning is proposed. DBSCAN algorithm not only divides the dataset into core points and edge points, but also divides part of the data into noise points to achieve the effect of denoising. In the core part, the dimensionality of the data is reduced by using stacking auto-encoders (SAE), and the localization task is accomplished by using a deep neural network (DNN) with an adaptive learning rate. At the edge points, the random forest (RF) algorithm is used to complete the localization task. Finally, the proposed architecture is verified on the UJIIndoorLoc dataset. The experimental results show that our positioning accuracy does not exceed 1.5 m with a probability of less than 87.2% at the edge point, and the time is only 32 ms; the positioning accuracy does not exceed 1.5 m with a probability of less than 98.8% at the core point. Compared with indoor positioning algorithms such as multi-layer perceptron and K Nearest Neighbors (KNN), good results have been achieved.

The contributions of mesoderm-derived cells in liver development.

The liver is an indispensable organ for metabolism and drug detoxification. The liver consists of endoderm-derived hepatobiliary lineages and various mesoderm-derived cells, and interacts with the surrounding tissues and organs through the ventral mesentery. Liver development, from hepatic specification to liver maturation, requires close interactions with mesoderm-derived cells, such as mesothelial cells, hepatic stellate cells, mesenchymal cells, liver sinusoidal endothelial cells and hematopoietic cells. These cells affect liver development through precise signaling events and even direct physical contact. Through the use of new techniques, emerging studies have recently led to a deeper understanding of liver development and its related mechanisms, especially the roles of mesodermal cells in liver development. Based on these developments, the current protocols for in vitro hepatocyte-like cell induction and liver-like tissue construction have been optimized and are of great importance for the treatment of liver diseases. Here, we review the roles of mesoderm-derived cells in the processes of liver development, hepatocyte-like cell induction and liver-like tissue construction.

Integrated, Highly Flexible, and Tailorable Thermoelectric Type Temperature Detectors Based on a Continuous Carbon Nanotube Fiber.

As possible alternatives to traditional thermoelectric (TE) materials, carbon nanomaterials and their hybrid materials have great potential in the future application of flexible and lightweight temperature detection. In this work, an integrated, highly flexible, and tailorable TE temperature detector with high performance has been fabricated based on a continuous single-walled carbon nanotube (SWCNT) fiber. The detector consists of more than one pairs of thermocouples composed of p-type SWCNT fiber and n-type SWCNT hybrid fiber in situ doped by polyethylenimine. Due to the node contact mechanism of the detection, the sensitivity of the detector can be improved with the increase of the number of p-n thermocouples, independent of the length of the thermocouple. The temperature detection process of the detector has been studied in detail. In particular, the integrated and flexible detector can be divided into several sub-detectors easily by cutting, illustrating the prospect of large-scale preparation of this kind of novel temperature detectors. Its high flexibility ensures the detector to maintain excellent detection performance after 15 000 bending circles. Furthermore, the as-designed TE type temperature detector demonstrates a great application promise for real-time temperature detection and temperature change sensing even in complex surface and harsh environment.

Tumor-Targeted Delivery of Bufalin-Loaded Modified Albumin-Polymer Hybrid for Enhanced Antitumor Therapy and Attenuated Hemolysis Toxicity and Cardiotoxicity.

A novel albumin polymer hybrid with a core-shell structure was designed to target delivery of bufalin, which is an antineoplastic monomer with serious cardiotoxicity. The sheath layer was composed of ursodeoxycholic acid (UA)-modified bovine serum albumin (UA-BSA), while the stable core consisted of poly n-butyl cyanoacrylate (PBCA) nanoparticles. The UA-BSA was synthetized, and the substitution degree was characterized. The physical properties of bufalin-loaded UA-modified protein-PBCA nanocomplexes (BF-uPPNCs), such as morphology, particle size, and encapsulation efficiency, were evaluated. FTIR and DSC revealed the bufalin to be in an amorphous state. Furthermore, the in vitro release study indicated a sustained release profile of BF-uPPNCs. The MTT and cellular uptake study demonstrated that BF-uPPNCs significantly improved the inhibitory effect of the bufalin accompanied with an enhanced cell uptake capacity on HepG2 cells. In addition, in vivo research demonstrated that BF-uPPNCs had a better antitumor effect coupled with improved therapeutic effect, and reduced hemolysis, vascular irritation, and cardiotoxicity. This work therefore presented a novel albumin polymer hybrid with favorable stability, efficient tumor-targeted delivery potential, and side effect reduction ability, which can be a potential vehicle for an anticancer drug.

Application of R2* and Apparent Diffusion Coefficient in Estimating Tumor Grade and T Category of Bladder Cancer.

OBJECTIVE. The objective of our study was to compare the feasibility of R2* and apparent diffusion coefficient (ADC) for differentiating tumor grade and T category of bladder cancer. SUBJECTS AND METHODS. In this prospective study, 58 patients with pathologically confirmed bladder cancers underwent pretreatment T2*-weighted imaging and DWI on a 3-T MRI unit. The apparent transverse relaxation rate R2*, which is derived from T2*-weighted imaging, and ADC, which is derived from DWI, were calculated and compared between low- and high-grade bladder cancers as well as between non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs) using the Mann-Whitney U test. The diagnostic performances of R2*, ADC, and the combination of R2* and ADC were evaluated through an ROC analysis. RESULTS. Significant differences were found in R2* (mean ± SD, 16.55 ± 5.54 vs 20.96 ± 7.75 s-1; p = 0.001) and ADC (1.62 ± 0.31 vs 1.33 ± 0.21 × 10-3 mm2/s; p < 0.001) between lowand high-grade bladder cancers. R2* was significantly higher (22.56 ± 8.41 vs 18.06 ± 6.46 s-1; p = 0.008) and ADC was considerably lower (1.21 ± 0.18 vs 1.53 ± 0.27 × 10-3 mm2/s; p < 0.001) in MIBCs than in NMIBCs. The AUCs for differentiating low-from high-grade groups were 0.714 using R2* and 0.779 using ADC. AUCs for distinguishing between NMIBC and MIBC groups using R2* and ADC were 0.682 and 0.850, respectively. CONCLUSION. In addition to ADC, R2* can be used as a quantitative imaging biomarker to provide additional information for tumor characterization of bladder cancer.

Prospective comparison of diffusion-weighted magnetic resonance enterography and contrast enhanced computed tomography enterography for the detection of ileocolonic Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic and relapsing course with various status of different segments, and there were no investigations comparing the lesion detection between magnetic resonance (MR) and computed tomography (CT) in term of the severity of CD. We aim to assess the performances of diffusion-weighted MR enterography (DW-MRE) and contrast enhanced CT enterography (CTE) for detecting different grade lesions in ileocolonic CD. METHODS: Forty-one consecutive patients finally diagnosed with ileocolonic CD were included. All the patients prospectively underwent DW-MRE, contrast enhanced CTE, and ileocolonoscopy within 2 weeks. DW-MRE and CTE images were interpreted for the presence or absence of active CD segments by two experienced radiologists independently. Ileocolonic segments (terminal ileum, right colon, transverse colon, left colon, and rectum) were graded as inactive (0-2), mild (3-6), or moderate-severe (≥ 7) by the simplified endoscopic score for CD (SES-CD). Diagnostic efficiencies of DW-MRE and CTE for mild and/or moderate-severe CD segments were calculated and compared, using ileocolonoscopy as reference standard. RESULTS: According to SES-CD, 190 ileocolonic segments from 41 CD patients were scored as 91 inactive, 68 mild, and 31 moderate-severe CD lesions. The sensitivity of DW-MRE for detecting active from inactive segments was higher than that of CTE, and the specificities of them had no significant differences. As for the subgroup analysis, DW-MRE was more sensitive for mild CD lesions than CTE (76.5% vs 60.3%; P = 0.019), while the sensitivities for moderate-severe CD were similar between these two modalities (96.8% for DW-MRE and 93.5% for CTE; P = 1.00). CONCLUSIONS: Both DW-MRE and CTE had comparably excellent performances for moderate-severe CD detection; DW-MRE demonstrated better sensitivity in mild lesions compared with CTE and could be more suitable for the diagnosis of mild CD.

Prevalence of Clonorchis sinensis infection in fish in South-East Asia: A systematic review and meta-analysis.

Clonorchis sinensis, an important fish-borne zoonotic trematode, is widely distributed in South-East Asia, especially in China. Infections from human and animal reservoir hosts occur due to the consumption of raw or undercooked fish with C. sinensis metacercariae. This study aimed to evaluate the prevalence of C. sinensis metacercariae in fish in South-East Asia via systematic review and meta-analysis. We searched PubMed, ScienceDirect, China National Knowledge Infrastructure, Wanfang and Chongqing VIP databases for studies published between 1976 and 2020 that are related to the prevalence of C. sinensis metacercariae in fish. Studies were screened with keywords based on inclusion and exclusion criteria. Seventy-one eligible articles were identified, covering three countries: China, Korea and Vietnam. The pooled prevalence of C. sinensis metacercariae in fish from South-East Asia was 30.5%, with 35.1% in China, 29.7% in Korea and 8.4% in Vietnam. In subgroup analyses of climate, season, water source and publication date, the highest prevalence was identified in the Dwb climate type (43.3%), summer (70.2%), river (34.5%) and pre-2001 publications (38.9%), respectively. In comparison, the lowest prevalence was found in the Dfa climate type (14.5%), winter (19.5%), lake (8.0%) and post-2001 publications (23.8%). Meta-regression results indicated that country (p = .009), the published time (p = .035) and water source subgroups (p = .003) may be the source of heterogeneity. Overall, our study indicates that a high prevalence of C. sinensis infections occurs in fish in China, Korea and Vietnam, illuminating a significant public health concern in these countries.

An impedimetric immunosensor for determination of porcine epidemic diarrhea virus based on the nanocomposite consisting of molybdenum disulfide/reduced graphene oxide decorated with gold nanoparticles.

An electrochemical immunosensor for the determination of porcine epidemic diarrhea virus (PEDV) is described. It was manufactured by using gold nanoparticles/molybdenum disulfide/reduced graphene oxide nanocomposites modified on the surface of a glassy carbon electrode (GCE). The independently developed monoclonal antibody of PEDV-2C11 was immobilized on the modified electrode at site of gold nanoparticles provided in the nanocomposites. The concentration of PEDV was quantified by measuring the changes in the charge transfer resistance of the electrode before and after the immunoreaction between antigen-antibody by using hexacyanoferrate(II)/(III) as the redox probe. The frequency range was 10-1 to 105 Hz at the amplitude of 10 mV and an applied potential of + 0.180 V. Based on the immunoreaction between PEDV antigen and PEDV-2C11 antibody in 0.1 M phosphate buffer containing 0.1 M KCl at 37.5 °C for 140 min, the relative change in impedance was proportional to the logarithmic value of PEDV concentrations in the range of 82.5 to 1.65 × 104 TCID50 mL-1. Good reproducibility, stability, and specificity of the proposed immunosensor were obtained. It was successfully applied to the determination of PEDV in the spiked sample. Graphical abstractSchematic representation. a The preparation of AuNP/MoS2/rGO composites. b Representation of modification and functioning of the label-free electrochemical immunosensor and the electrochemical impedimetric response obtained before (a) and after (b) incubation of PEDV.