Nanobodies in cytokine­mediated immunotherapy and immunoimaging (Review).

Cytokines are the main regulators of innate and adaptive immunity, mediating communications between the cells of the immune system and regulating biological functions, including cell motility, differentiation, growth and apoptosis. Cytokines and cytokine receptors have been used in the treatment of tumors and autoimmune diseases, and to intervene in cytokine storms. Indeed, the use of monoclonal antibodies to block cytokine­receptor interactions, as well as antibody­cytokine fusion proteins has exhibited immense potential for the treatment of tumors and autoimmune diseases. Compared with these traditional types of antibodies, nanobodies not only maintain a high affinity and specificity, but also have the advantages of high thermal stability, a high capacity for chemical manipulation, low immunogenicity, good tissue permeability, rapid clearance and economic production. Thus, nanobodies have extensive potential for use in the diagnosis and treatment of cytokine­related diseases. The present review summarizes the application of nanobodies in cytokine­mediated immunotherapy and immunoimaging.

Preparation of Thin Film Composite (TFC) Membrane with DESPs Interlayer and Its Forward Osmosis (FO) Performance for Organic Solvent Recovery.

To explore the application of forward osmosis (FO) technology in the organic solvent recovery field, we prepared a new solvent-resistant triple layer thin film composite (TFC) membrane on the PI (polyimide) substrate. The deep eutectic supramolecular polymers (DESPs) interlayer was constructed on the substrate to improve the separation performance and solvent resistance. DESPs interlayer was formed by mixing and heating with cyclodextrin as the hydrogen bond acceptor and L-malic acid as the hydrogen bond donor. The chemical changes, surface property and morphology of the composite membrane with DESPs interlayer were characterized. The separation performance and stability of the triple layer composite membrane in organic solvent FO were studied. For the monascorubrin-ethanol system, the permeation flux of TFC/DESPs5-PI membrane could reach 9.51 LMH while the rejection rate of monascorubrin was 98.4% (1.0 M LiCl/ethanol as draw solution), which was better than the pristine membrane. Therefore, this solvent-resistant triple layer composite FO membrane has good potential for the recovery of organic solvents.

Detection of the communicating accessory bile duct in laparoscopic resection of residual gallbladder by the combination of the indocyanine green fluorescence cholangiography and the intraoperative cholangiography: A case report.

BACKGROUND: The partial cholecystectomy may be performed while in complicated laparoscopic cholecystectomy (LC). Biliary anomalies especially the accessory bile duct are established high risk of bile duct injury (BDI) in LC. Laparoscopic resection of residual gallbladder is a challenging procedure and extremely vulnerable to BDI. We report the execution of a laparoscopic resection of residual gallbladder with a communicating accessory bile duct using indocyanine green (ICG) fluorescence cholangiography and the intraoperative cholangiography (IOC). A case that has not been reported previously. PRESENTATION OF CASE: A 29-year-old female with history of laparoscopic partial cholecystectomy was admitted in our hospital. Magnetic resonance cholangiopancreatography (MRCP) revealed the residual gallbladder with an accessory bile duct. Considering the complexity of this patient, we performed a laparoscopic surgery using ICG fluorescence cholangiography. ICG was injected intravenously 1 h before the surgery, the residual gallbladder and the extrahepatic biliary structures including the accessory bile duct were imaged in green in fluorescence imaging that could be recognized clearly. IOC revealed that residual gallbladder communicated with intrahepatic bile duct through the accessory bile duct and drained into the common bile duct (CBD). The entire procedure was performed smoothly and successfully without bile duct injuries. DISCUSSION: Laparoscopic resection of residual gallbladder is a challenging procedure. Fluorescence cholangiography using ICG is regarded as a novel technique that could provide a real-time imaging intraoperative, which allowed to recognize and identify the residual gallbladder and the extrahepatic bile duct. IOC is also important in identifying a communicating accessory bile duct. Under the guidance of them, we completed this laparoscopic surgery. CONCLUSIONS: The combination of fluorescence cholangiography using ICG and IOC have profound significance in complicated LC.

Clinical outcomes of percutaneous transhepatic biliary drainage at different Couinaud's hepatic entry segments for treating obstructive jaundice.

Introduction: Percutaneous transhepatic biliary drainage (PTBD) is a common procedure for biliary obstructive jaundice caused by biliary tract obstruction. In clinical practice, PTBD can be carried out at right- or left-sided approach. However, different hepatic entry site may affect success rates and complications. Couinaud classification of liver anatomy further divides the liver into functionally independent segments (segment 2/3, segment 5/6, and segment 7/8). Therefore, this study aimed to elucidate whether different Couinaud hepatic segments as PTBD entry site are associated with high PTBD success and low complications. Methods: A total of 617 patients who underwent PTBD were retrospectively reviewed. Univariate and multivariate logistic regression analyses were performed to identify entry segments associated with PTBD success, bilirubin reduction, and complications. Results: With higher hepatic segment of PTBD entry site (segment 2/3, 5/6, and 7/8), the trend of PTBD success rate (82.0%, 71.7% and 60.7%; P<0.001) and bilirubin reduction (93.2%, 89.5%, and 82.0%; P=0.012) decreased. Furthermore, PTBD entry at segment 7/8 (42.6%) had highest complication rate than segment 5/6 (6.4%) and 2/3 (9.4%). Univariate and multivariate logistic regression analyses showed that PTBD entry segment was an independent factor associated with PTBD success, bilirubin reduction, and complications. Compared to segment 7/8, segment 2/3 and 5/6 had higher odds of PTBD success (aOR=2.699 and aOR=1.454, respectively) and bilirubin reduction (aOR=3.472 and aOR=2.361, respectively) and associated with lower risk of complications (aOR=0.143 and aOR=0.098, respectively). No independent risk factor for PTBD success and bilirubin reduction were identified in intrahepatic tumors. Moreover, for extrahepatic tumors, PTBD entry at segment 2/3 and segment 5/6 was more likely achieve PTBD success (aOR=3.037 and aOR=1.929, respectively), bilirubin reduction (aOR=3.069 and aOR=3.515) and low complications (aOR=0.102 and aOR=0.126, respectively). Discussion: Good clinical outcomes were observed for PTBD entry at segments 5/6 and 2/3. In contrast, segment 7/8 had the lowest success rate, smallest bilirubin reduction, and the highest complication rate. For patients with obstructive jaundice, PTBD entry in hepatic segments 2/3 and 5/6 is recommended to achieve high success rates and low complications.

Effectiveness and safety of ultrasound-guided percutaneous microwave ablation for hepatic alveolar echinococcosis.

BACKGROUND: Microwave ablation (MWA) is a popular therapy for liver malignant tumor in recent years. Few studies have been conducted on its use in the treatment of hepatic alveolar echinococcosis (HAE). The study aims to evaluate the efficacy and safety of MWA in the treatment of HAE. METHODS: This study analyzed the data of 45 patients (mean age, 38 ± 2 years; 24 males) diagnosed with HAE and underwent MWA treatment between June 2014 to December 2019. The patients after MWA were examined by CT or MRI [follow-up: 32 months (IQR 23-48.5)] to determine whether the lesions were relapsed and to evaluate the therapeutic effect of MWA. The safety of MWA was evaluated by monitoring postoperative complications. Clinical data, such as patient demographics, imaging features of the lesions, relevant findings of laboratory tests before and after ablation, and information related to ablation, were collected and analyzed. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare relevant laboratory indicators before and after MWA. RESULTS: MWA was applied to 57 HAE lesions in 45 patients. The median size of lesions was 3.42 cm (IQR2.85-4.41). The rate of complete ablation was 100% (57/57). The median follow-up time was 32 months (IQR 23-48.5). The recurrence rate was 13% (6/45), and the median time of recurrence was 22 months. The rate of minor complications was 11.1% (5/45), and there were no major complications and deaths. Compared to preoperative, ALB, RBC, HBG, and PLT were decreased (p < 0.001); ALT, TB, DB, and WBC were increased (p < 0.001); and no statistically difference in PT, APTT, and INR (p > 0.05). CONCLUSIONS: MWA might be a safe and effective way to cure HAE. Meanwhile, it provides a new option and a new way of thinking about treatment for patients with HAE.

Analysis of the efficacy of microwave ablation in the treatment of early hepatic alveolar echinococcosis: A propensity score matching based study.

BACKGROUND: To explore the efficacy of microwave ablation (MWA) in the treatment of hepatic alveolar echinococcosis (HAE) with a diameter of ≤5 cm. METHOD: From June 2014 to January 2020, patients diagnosed with HAE were retrospectively analyzed. After balancing the confounding factors by propensity score matching (PSM) , the patients were divided into MWA group (n = 20) and radical operation group (n = 20) by 1:1 matching. The safety and effectiveness of MWA were assessed by comparing the differences between the two groups in terms of postoperative general laboratory indices, grading of postoperative complications, length of postoperative hospitalization, the outcome of treatment, and disease recurrence. RESULT: After PSM, all confounders were not statistically different (P>0.05) . Compared with the radical surgery group, patients in the MWA group had lower postoperative ALT and WBC elevations (P<0.001) , shorter postoperative hospital stay (P<0.001) ) , lower hospital costs (P<0.001) . The effective rate of the two groups was 100%. There was no statistical difference in the incidence of postoperative complications and recurrence rate (P>0.05). CONCLUSION: MWA is a safe and effective means of treating HAE ≤ 5 cm in diameter.

Automated Stanford classification of aortic dissection using a 2-step hierarchical neural network at computed tomography angiography.

OBJECTIVES: This study aimed to evaluate the feasibility of automatic Stanford classification of classic aortic dissection (AD) using a 2-step hierarchical neural network. METHODS: Between 2015 and 2019, 130 arterial phase series (57 type A, 43 type B, and 30 negative cases) in aortic CTA were collected for the training and validation. A 2-step hierarchical model was built including the first step detecting AD and the second step predicting the probability (0-1) of Stanford types. The model's performance was evaluated with an off-line prospective test in 2020. The sensitivity and specificity for Stanford type A, type B, and no AD (Sens A, B, N and Spec A, B, N, respectively) and Cohen's kappa were reported. RESULTS: Of 298 cases (22 with type A, 29 with type B, and 247 without AD) in the off-line prospective test, the Sens A, Sens B, and Sens N were 95.45% (95% confidence interval [CI], 77.16-99.88%), 79.31% (95% CI, 60.28-92.01%), and 93.52% (95% CI, 89.69-96.25%), respectively. The Spec A, Spec B, and Spec N were 98.55% (95% CI, 96.33-99.60%), 94.05% (95% CI, 90.52-96.56%), and 94.12% (95% CI, 83.76-98.77%), respectively. The classification rate achieved 92.28% (95% CI, 88.64-95.04%). The Cohen's kappa was 0.766 (95% CI, 0.68-0.85; p < 0.001). CONCLUSIONS: Stanford classification of classic AD can be determined by a 2-step hierarchical neural network with high sensitivity and specificity of type A and high specificity in type B and no AD. KEY POINTS: • The Stanford classification for aortic dissection is widely adopted and divides it into Stanford type A and type B based on the ascending thoracic aorta dissected or not. • The 2-step hierarchical neural network for Stanford classification of classic aortic dissection achieved high sensitivity (95.45%) and specificity (98.55%) of type A and high specificity in type B and no aortic dissection (94.05% and 94.12%, respectively) in 298 test cases. • The 2-step hierarchical neural network demonstrated moderate agreement (Cohen's kappa: 0.766, p < 0.001) with cardiovascular radiologists in detection and Stanford classification of classic aortic dissection in 298 test cases.

Automated Radiology Alert System for Pneumothorax Detection on Chest Radiographs Improves Efficiency and Diagnostic Performance.

We aimed to set up an Automated Radiology Alert System (ARAS) for the detection of pneumothorax in chest radiographs by a deep learning model, and to compare its efficiency and diagnostic performance with the existing Manual Radiology Alert System (MRAS) at the tertiary medical center. This study retrospectively collected 1235 chest radiographs with pneumothorax labeling from 2013 to 2019, and 337 chest radiographs with negative findings in 2019 were separated into training and validation datasets for the deep learning model of ARAS. The efficiency before and after using the model was compared in terms of alert time and report time. During parallel running of the two systems from September to October 2020, chest radiographs prospectively acquired in the emergency department with age more than 6 years served as the testing dataset for comparison of diagnostic performance. The efficiency was improved after using the model, with mean alert time improving from 8.45 min to 0.69 min and the mean report time from 2.81 days to 1.59 days. The comparison of the diagnostic performance of both systems using 3739 chest radiographs acquired during parallel running showed that the ARAS was better than the MRAS as assessed in terms of sensitivity (recall), area under receiver operating characteristic curve, and F1 score (0.837 vs. 0.256, 0.914 vs. 0.628, and 0.754 vs. 0.407, respectively), but worse in terms of positive predictive value (PPV) (precision) (0.686 vs. 1.000). This study had successfully designed a deep learning model for pneumothorax detection on chest radiographs and set up an ARAS with improved efficiency and overall diagnostic performance.

Improvement of multisource localization of magnetic particles in an animal.

In this simulation work, the linearized Bregman iterative algorithm was applied to solve the magnetic source distribution problem of a magnetic particle imaging (MPI) system for small animals. MPI system can apply an excitation magnetic field, and the induced magnetic field from the magnetic nanoparticles (MNPs) can be detected by the sensors of MPI system. With a gaussian distribution source at the upper side of the mouse brain, sensors set above the mouse brain and the constant excitation magnetic field, the average deviation of the calculated source distribution from the multiplane scanning along the axis away from the mouse brain and the closest plane scanning are 2.78 × 10-3 and 2.84 × 10-3 respectively. The simulated result showed that combination of multiplane scanning hardly improves the accuracy of the source localization. In addition, a gradient scan method was developed that uses gradient magnetic field to scan the mouse brain. The position of the maximum of the lead field matrix will be controlled by the gradient field. With a set up gaussian distribution source at the bottom of the mouse brain, the average deviation of the calculated source distribution from the gradient scan method and the constant field are 4.42 × 10-2 and 5.05 × 10-2. The location error from the two method are 2.24 × 10-1 cm and 3.61 × 10-1 cm. The simulation showed that this method can improve the accuracy compared to constant field when the source is away from the sensor and having a potential for application.

lncRNA DGCR5 inhibits the proliferation of colorectal cancer cells by downregulating miR-21.

Long non-coding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) serves roles as a tumor suppressor or oncogene in different types of cancer. The current study aimed to explore the role of DGCR5 in colorectal cancer (CRC). It was revealed that the expression of DGCR5 was downregulated, while microRNA (miR)-21 was upregulated in CRC. The expression level of DGCR5 in tumor tissue decreased, while expression levels of miR-21 increased, with advancing stages of the disease. The expression levels of DGCR5 and miR-21 were inversely associated in tumor tissues. In CRC cells in vitro, miR-21 overexpression failed to significantly affect DGCR5, while DGCR5 overexpression resulted in reduced expression levels of miR-21. DGCR5 overexpression showed no significant effects on cancer cell migration and invasion, but suppressed cancer cell proliferation in vitro. miR-21 overexpression increased cancer cell proliferation and attenuated the effects of DGCR5 overexpression. Therefore, lncRNA DGCR5 may inhibit the proliferation of CRC cells by downregulating miR-21.

Visible-Light-Mediated Decarboxylative Alkylation Cascade Cyano Insertion/Cyclization of N-Arylacrylamides under Transition-Metal-Free Conditions.

The visible-light-mediated decarboxylative functionalization of aliphatic carboxylic acids using organocatalysts has rarely been reported. This study represented an environmentally benign decarboxylation method involving the combination of eosin Y and (NH4)2S2O8. This system converted aliphatic carboxylic acids to alkyl radicals, followed by their addition to the carbon-carbon double bond of the N-arylacrylamide cascade cyano insertion/cyclization to construct alkylated phenanthridines in moderate to good yields under photoredox catalysis.

Characterizations of Anti-Alpha-Fetoprotein-Conjugated Magnetic Nanoparticles Associated with Alpha-Fetoprotein for Biomedical Applications.

In this work, we report characterizations of biofunctionalized magnetic nanoparticles (BMNPs) associated with alpha-fetoprotein (AFP) for biomedical applications. The example BMNP in this study is anti-alpha-fetoprotein (anti-AFP) conjugated onto dextran-coated Fe3O4 labeled as Fe3O4-anti-AFP, and the target is AFP. We characterize magnetic properties, such as increments of magnetization ΔMH and effective relaxation time Δτeff in the reaction process. It is found that both ΔMH and Δτeff are enhanced when the concentration of AFP, ФAFP, increases. The enhancements are due to magnetic interactions among BMNPs in magnetic clusters, which contribute extra MH after the association with MH and in turn enhance τeff. The screening of patients carrying hepatocellular carcinoma (HCC) is verified via ΔMH/MH. The proposed method can be applied to detect a wide variety of analytes. The scaling characteristics of ΔMH/MH show the potential to develop a vibrating sample magnetometer system with low field strength for clinic applications.

Transmission of 20-Gb/s OFDM signals occupying 7-GHz license-free band at 60 GHz using a RoF system employing frequency sextupling optical up-conversion.

This work describes a proposed 60-GHz radio-over-fiber (RoF) system employing a frequency sextupling optical up-conversion scheme. Based on the modified single sideband modulation scheme, spectrally efficient vector signals were transmitted with no performance degradation due to dispersion-induced fading. Wavelength-division- multiplexed optical up-conversion can be realized using the proposed system. Since the required transmitter bandwidth is significantly reduced, radio-frequency components with lower bandwidth and higher reliability can be utilized. Both 13.75-Gb/s QPSK-OFDM and 20.625-Gb/s 8QAM-OFDM signals were experimentally demonstrated. After transmission over 25-km of standard single mode fiber, no significant received power penalty was observed.

WDM up-conversion employing frequency quadrupling in optical modulator.

This work presents an optical up-conversion system with frequency quadrupling for wavelength-division-multiplexing (WDM) communication systems using a dual-parallel Mach-Zehnder modulator without optical filtering. Four-channel 1.25-Gb/s wired fiber-to-the-x (FTTx) and wireless radio-over-fiber (RoF) signals are generated and transmitted simultaneously. Moreover, the decline in receiver sensitivities due to Mach-Zehnder modulator bias drifts is also investigated. Receiver power penalties of the 20-GHz up-converted WDM signals and baseband (BB) FTTx signals are less than 1 dB when bias deviation voltage is less the 20% of the half-wave voltage. After transmission over a 50-km SSMF, the receiver power penalties of both the BB and 20-GHz RF OOK signals are less than 1 dB. Notably, 60-GHz optical up-conversion can be achieved using 15-GHz radio frequency (RF) components and equipment.