Charge Dynamics Engineering Sparks Hetero-Interfacial Polarization for an Ultra-Efficient Microwave Absorber with Mechanical Robustness.

Microwave absorbers with high efficiency and mechanical robustness are urgently desired to cope with more complex and harsh application scenarios. However, manipulating the trade-off between microwave absorption performance and mechanical properties is seldom realized in microwave absorbers. Here, a chemistry-tailored charge dynamic engineering strategy is proposed for sparking hetero-interfacial polarization and thus coordinating microwave attenuation ability with the interfacial bonding, endowing polymer-based composites with microwave absorption efficiency and mechanical toughness. The absorber designed by this new conceptual approach exhibits remarkable Ku-band microwave absorption efficiency (-55.3 dB at a thickness of 1.5 mm) and satisfactory effective absorption bandwidth (5.0 GHz) as well as desirable interfacial shear strength (97.5 MPa). The calculated differential charge density depicts the uneven distribution of space charge and the intense hetero-interfacial polarization, clarifying the structure-performance relationship from a theoretical perspective. This work breaks through traditional single performance-oriented design methods and ushers a new direction for next-generation microwave absorbers.

Peritoneal Gene Transfection of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand for Tumor Surveillance and Prophylaxis.

Peritoneal metastasis is very common in gastrointestinal, reproductive, and genitourinary tract cancers in late stages or postsurgery, causing poor prognosis, so effective and nontoxic prophylactic strategies against peritoneal metastasis are highly imperative. Herein, we demonstrate the first gene transfection as a nontoxic prophylaxis preventing peritoneal metastasis or operative metastatic dissemination. Lipopolyplexes of TNF-related-apoptosis-inducing-ligand (TRAIL) transfected peritonea and macrophages to express TRAIL for over 15 days. The expressed TRAIL selectively induced tumor cell apoptosis while exempting normal tissue, providing long-term tumor surveillance. Therefore, tumor cells inoculated in the pretransfected peritoneal cavity quickly underwent apoptosis and, thus, barely formed tumor nodules, significantly prolonging the mouse survival time compared with chemotherapy prophylaxis. Furthermore, lipopolyplex transfection showed no sign of toxicity. Therefore, this peritoneal TRAIL-transfection is an effective and safe prophylaxis, preventing peritoneal metastasis.

Smartphone-Based Electrochemical Biosensors for Directly Detecting Serum-Derived Exosomes and Monitoring Their Secretion.

Exosomes are potential biomarkers, which play an important role in early diagnosis and prognosis prediction of cancer-related diseases. Nevertheless, direct quantification of exosomes in biological fluid, especially in point-of-care tests (POCTs), remains extremely challenging. Herein, we developed a sensitive and portable electrochemical biosensor in combination with smartphones for quantitative analysis of exosomes. The improved double-antibody sandwich method-based poly-enzyme signal amplification was adopted to detect exosomes. We could detect as low as 7.23 ng of CD63-positive exosomes in 5 µL of serum within 2 h. Importantly, we demonstrated that the biosensor worked well with microliter-level serum and cell culture supernatant. The biosensor holds great potential for the detection of CD-63-expressing exosomes in early diagnosis of prostate disease because CD63-positive exosomes were less detected from the prostate patient serum. Also, the biosensor was used to monitor the secretion of exosomes with the drug therapy, showing a close relationship between the secretion of exosomes and the concentration of cisplatin. The biosensing platform provides a novel way toward POCT for the diagnosis and prognosis prediction of prostate disease and other diseases via biomarker expression levels of exosomes.

Integrating Multi-Heterointerfaces in a 1D@2D@1D Hierarchical Structure via Autocatalytic Pyrolysis for Ultra-Efficient Microwave Absorption Performance.

Developing microwave absorption (MA) materials with ultrahigh efficiency and facile preparation method remains a challenge. Herein, a superior 1D@2D@1D hierarchical structure integrated with multi-heterointerfaces via self-assembly and an autocatalytic pyrolysis is designed to fully unlock the microwave attenuation potential of materials, realizing ultra-efficient MA performance. By precisely regulating the morphology of the metal organic framework precursor toward improved impedance matching and intelligently integrating multi-heterointerfaces to boosted dielectric polarization, the specific return loss value of composites can be effectively tuned and optimized to -1002 dB at a very thin thickness of 1.8 mm. These encouraging achievements shed fresh insights into the precise design of ultra-efficient MA materials.

Enhancing overall properties of epoxy-based composites using polydopamine-coated edge-carboxylated graphene prepared via one-step high-pressure ball milling.

Graphene (GN) nanofillers have been widely used to enhance the overall performance of polymer composites due to their various superior properties, which strongly rely on the uniform dispersion and strong interfacial bonding of GN with high-quality polymer matrices. In the present study, the strengthening and functional effects of polydopamine-coated edge-carboxylated graphene (p-ECG) on the mechanical, moisture-barrier and electromagnetic properties of epoxy (EP)-based composites were systematically evaluated. p-ECG was successfully prepared via one-step high-pressure ball milling through the edge-selective functionalization and exfoliation of pristine graphite in the presence of dry ice, followed by synchronous reduction and coating via the mild oxidative polymerization of mussel-inspired dopamine. p-ECG showed prominent advantages of a small sheet size, excellent dispersibility and high chemical reactivity in the EP matrix. Obvious enhancements were achieved in the tensile and flexural properties and moisture-barrier performance of EP composites as well as the interlaminar shear strength (ILSS) and transverse fiber bundle tensile (TFBT) strength of carbon fiber (CF)/EP composites, which confirmed the excellent dispersion and chemically strengthened interfacial bonding of p-ECG in the EP matrix. More importantly, p-ECG introduced onto the surface of desized CF led to significant enhancement in the electromagnetic interference (EMI) shielding capability of CF/EP composites, which was primarily ascribed to the polarization relaxation effect induced by the defects and functional groups in p-ECG as well as the increase in electrical conductivity derived from the "bridging effect" of p-ECG. Specifically, with p-ECG content of 0.5 wt%, the increments in tensile strength, TFBT strength, shielding effectiveness (total, SET) and shielding effectiveness (reflection loss, SER) were as high as 33.3, 34.3, 31.3 and 71.0%, respectively.

Quantitative proteomic study of myocardial mitochondria in urea transporter B knockout mice.

In previous research, we showed that 16-week-old urea transporter B (UT-B) null mice have an atrial-ventricular conduction block, and hypothesized myocardial mitochondrial dysfunction. To investigate the mechanism of this block, we examined the proteomic differences in the myocardial mitochondria of UT-B null and wild-type mice with nanoscale LC-MS/MS. Of 26 proteins clearly downregulated in the UT-B null mice, 15 are involved in complexes I, III, IV, and V of the respiratory chain, which would strongly reduce the activity of the electron transport chain. Excess electrons from complexes I and III pass directly to O2 to generate ROS and deplete ROS-scavenging enzymes. Myocardial intracellular ROS were significantly higher in UT-B null mice than in wild-type mice (p < 0.01), constituting an important cause of oxidative stress injury in the myocardia of UT-B null mice. The mitochondrial membrane potential (ΔΨm) was also lower in UT-B null mice than in wild-type mice (p < 0.05), causing oxidative phosphorylation dysfunction of complex V and insufficient ATP in the myocardial cells of UT-B null mice. HADHA (a trifunctional protein) and HSP60 were also downregulated in the UT-B null myocardial mitochondria. These results confirm that mitochondrial dysfunction underlies the pathogenesis of the atrial-ventricular conduction block in UT-B null mice.

Fracture mechanism of amorphous polymers at strain fields.

Owing to the wide application of polymeric materials, understanding the fracture mechanism of amorphous polymers at strain fields is a fundamentally important challenge. In this work, we use molecular dynamics simulations to investigate the uniaxial deformation of amorphous polyethylene and further monitor the polyethylene fracture process induced by stretching. Results indicate that the polyethylene systems with chain lengths of 600-800 united atoms exhibit the fracture behavior at a temperature T < 200 K and the strain of 1.0. Further study shows that in the stretching process, the disentanglement and orientation of chains lead to the formation of small cavities in the middle region of the system, and the small cavities subsequently form a large hole, causing the fracture of the whole system. Definitely, the fracture is determined by the two factors of mobility and entanglement of chains. The polyethylene systems with a high chain mobility or a high chain entanglement do not fracture. Finally, a schematic diagram is put forward to illustrate the fracture behavior.

Sinularin stabilizes FOXO3 protein to trigger prostate cancer cell intrinsic apoptosis.

Sinularin, a natural product that purified from soft coral, exhibits anti-tumor effects against various human cancers. However, the mechanisms are not well understood. In this study, we demonstrated that Sinularin inhibited the viability of human prostate cancer cells in a dose-dependent manner and displayed significant cytotoxicity only at high concentration against normal prostate epithelial cell RWPE-1. Flow cytometry assay demonstrated that Sinularin induced tumor cell apoptosis. Further investigations revealed that Sinularin exerted anti-tumor activity through intrinsic apoptotic pathway along with up-regulation of pro-apoptotic protein Bax and PUMA, inhibition of anti-apoptotic protein Bcl-2, mitochondrial membrane potential collapses, and release of mitochondrial proteins. Furthermore, we illustrated that Sinularin induced cell apoptosis via up-regulating PUMA through inhibition of FOXO3 degradation by the ubiquitin-proteasome pathway. To explore how Sinularin suppress FOXO3 ubiquitin-proteasome degradation, we tested two important protein kinases AKT and ERK that regulate FOXO3 stabilization. The results revealed that Sinularin stabilized and up-regulated FOXO3 via inhibition of AKT- and ERK1/2-mediated FOXO3 phosphorylation and subsequent ubiquitin-proteasome degradation. Our findings illustrated the potential mechanisms by which Sinularin induced cell apoptosis and Sinularin may be applied as a therapeutic agent for human prostate cancer.

Intrinsically reactive hyperbranched interface governs graphene oxide dispersion and crosslinking in epoxy for enhanced flame retardancy.

Enhancing the flame retardancy of epoxy (EP) resins typically entailed a trade-off with other physical properties. Herein, hyperbranched poly(amidoamine) (HPAA) and phytic acid (PA) were used to functionalize graphene oxide (GO) via electrostatic self-assembly in water to prepare a phosphorus-nitrogen functionalized graphene oxide nanosheet (PN-GOs), which could be utilized as high efficient flame-retardant additive of epoxy resin without sacrificing other properties. The PN-GOs demonstrated improved dispersion and compatibility within the EP matrix, which resulted in significant concurrent enhancements in both the mechanical performance and flame-retardant properties of the PN-GOs/EP nanocomposites over virgin EP. Notably, the incorporation of just 1.0 wt% PN-GOs yielded a 20.4, 6.4 and 42.7 % increases in flexural strength, flexural modulus and impact strength for the PN-GOs/EP nanocomposites, respectively. Furthermore, simultaneous reductions were achieved in the peak heat release rate (pHRR) by 60.0 %, total smoke production (TSP) by 43.0 %, peak CO production rate (pCOP) by 57.9 %, and peak CO2 production rate (pCO2P) by 63.9 %. This study presented a facile method for the design of GO-based nano flame retardants, expanding their application potential in polymer-matrix composites.

Methylation specific enzyme-linked oligonucleotide assays (MS-ELONA) for ultrasensitive DNA methylation analysis.

Methylation of the promoter region of cancer related genes plays a crucial role in the occurrence and development of cancer, and the degree of methylation has great potential for the early cancer diagnosis. At present, the technology used to quantify DNA methylation is mainly based on the DNA sequencing which are time-consuming and high-cost in the relating application. We have developed an ultrasensitive method of methylation specific enzyme-linked oligonucleotide assays (MS-ELONA) to detect and quantify the level of DNA methylation. We could detect as little as 2 pg of methylated DNA in the 100000-fold excess of unmethylated genes, and discriminate prostate cancer from benign prostatic hyperplasia (BPH) and control with serum samples. We also demonstrate the reversibility of DNA methylation modification by treatment with demethylation drugs. With 16-channel electrochemical work station, our research reveals a simple and inexpensive method to quantify the methylation level of specially appointed genes, and have the potential to be applied in the clinical research.

Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.

Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known. Methods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs. Results: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed. Conclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.

Carbon-Confined Two-Dimensional Sodiophilic Sites Boosted Dendrite-Free Sodium Metal Anodes.

Carbon-supported sodium metal anodes (SMAs) have attracted growing interest in next-generation energy storage applications. Sodiophilic sites on carbon hosts such as foreign metal/metal compounds are critical for suppressing Na dendrite growth. However, the foreign active materials are mostly restricted to nanoparticle-like structures, which suffer from severe agglomeration and low metal utilization. Here, we develop the carbon-encapsulated mosaic Fe3O4 nanosheets (Fe3O4@CNS) with two-dimensional (2D) active sites via the oriented attachment (OA) mechanism. Ultrathin Fe3O4 nanosheets not only endow the carbon hosts with a continuous 2D nucleation region and high metal utilization but also catalyze the formation of a stable solid electrolyte interphase (SEI) film. Additionally, carbon shells can protect the Fe3O4 against electrolyte exfoliation. As a result, the Fe3O4@CNS half cells achieve a cycle of up to 1800 h with an average Coulombic efficiency (CE) of 99.6% at 1.0 mA cm-2 and 1.0 mA h cm-2 and still stably cycle for 800 h with a high CE of 99.2% even at 3.0 mA cm-2 and 3.0 mA h cm-2. The Na@Fe3O4@CNS symmetric cells can last for more than 2200 h at 1.0 mA cm-2 and 1.0 mA h cm-2. And the Na3V2(PO4)3 || Na@Fe3O4@CNS full cells can attain a specific capacity of 86.6 mA h g-1 after 350 cycles at 1.0 A g-1 (∼8C), showing excellent cycle stability for practical applications. This work provides a new method to establish efficient 2D nucleation sites in the Na hosts.

Tyrosine kinase receptor RON activates MAPK/RSK/CREB signal pathway to enhance CXCR4 expression and promote cell migration and invasion in bladder cancer.

Bladder cancer (BC) is one of the most lethal malignancies worldwide. The poor survival may be due to a high proportion of tumor metastasis. RON and CXCR4 are the key regulators of cell motility in BC, while the relationship between RON and CXCR4 remains elusive. In the present study, immunohistochemistry analysis of BC and adjacent normal tissues found that higher RON expression was positively correlated with CXCR4 expression. Inhibiting and replenishing RON level were used to regulate CXCR4 expression, observing the effects on migration and invasion of BC cells. Overexpression of RON reversed the inhibited cell migration and invasion following siCXCR4 treatment. Conversely, overexpression of CXCR4 restored the inhibition of cell migration and invasion caused by shRON. The activation of RON-MAPK/RSK/CREB pathway was demonstrated in BC cells under MSP treatment. Dual luciferase and CHIP assay showed that p-CREB targeted CXCR4 by binding to its CRE sequence. RON knockdown suppressed BC tumor growth in xenograft mouse tumors, accompanied by reduced expression of CXCR4. In conclusion, our data adds evidence that RON, a membrane tyrosine kinase receptor, promotes BC migration and invasion not only by itself, but also by activating MAPK/RSK/CREB signaling pathway to enhance CXCR4 expression.

Bimetal-doped core-shell carbon derived from nickel-cobalt dual-ligand metal-organic framework for adjustable strong microwave absorption.

Metal-organic framework materials (MOF) have become a new generation of microwave absorption (MA) materials. However, it is still challenging to design an appropriate microstructure that can efficiently adjust the microwave absorbing characteristics. Herein, a novel bimetal-doped core-shell carbon derived from nickel-cobalt dual-ligand MOF has been successfully prepared. By changing the ratio of the second ligand, the morphology can change from sea urchin-like to rod-like and petal-like shapes, thereby regulating the final wave absorption performance of MOF derivatives. The Bi-MOF-1 exhibited strong microwave absorption (up to -70.70 dB), while Bi-MOF-2 presented broad effective absorption bandwidth (5.92 GHz). The analyses indicated that the excellent impedance matching can be attributed to the double-layer magnetic loss and multiple dielectric loss of the core-shell structure. This work provides a feasible approach for the design and preparation of functional composite structures based on MOF derivatives with controllable microwave absorbing properties.

Case report: Complete response of a bladder cancer patient with multiple hepatic and pelvic metastases treated by nab-paclitaxel combined with sintilimab.

This article described a patient with metastatic bladder cancer (mBC) who was successfully treated with nab-paclitaxel plus sintilimab. Localized muscle-invasive bladder cancer (MIBC) was discovered in a 56-year-old man who received radical cystectomy and platinum-based adjuvant chemotherapy. Eleven months after cystectomy, this patient developed numerous hepatic and pelvic metastases and progressed to mBC. The patient was given an anti-PD-1 antibody (sintilimab 200mg, q3w) in combination with Nab-paclitaxel (100mg, qw) for mBC. Complete remission (CR) was achieved after nine cycles of therapy, and the patient had no severe side effects during the treatment. The disease remained in CR after 41 months of follow-up. This case suggests that nab-paclitaxel combined with sintilimab is a safe and effective option in treatment of mBC.

Atypical granular cell tumor of the urinary bladder: A case report.

BACKGROUND: Granular cell tumor (GCT) is a neurogenic tumor mainly occurring in the head and neck. GCT in the genitourinary system is extremely rare and only sporadic cases of urinary bladder GCT have been reported. Most urinary bladder GCT cases are benign and only two malignant cases have been reported. Due to its rarity, no consensus criteria for the treatment of urinary bladder GCT are available at present. CASE SUMMARY: A 62-year-old Chinese woman was found to have a urinary bladder tumor without any clinical manifestations on physical examination. Cystoscopy revealed a semispherical shaped lesion measuring approximately 4.0 cm in diameter at the junction of the left wall and roof of the bladder, which was covered with normal bladder mucosa. Computed tomography scan demonstrated a high-density lesion on the left wall of the bladder, measuring approximately 2.9 cm × 2.4 cm with clear boundaries. Contrast-enhanced pelvic magnetic resonance imaging revealed a space-occupying lesion on the left wall of the bladder (non-mucosal origin/ external pressure), which was preliminarily suspected to be a desmoplastic fibroma or leiomyoma. In the context of the above findings, a pre-operative diagnosis of bladder leiomyoma was made. The patient consequently underwent a laparoscopic partial cystectomy. The resected bladder mass looked yellowish and well-demarcated, measuring 4.0 cm × 3.5 cm and infiltrated the muscular layer. The diagnosis of urinary bladder GCT was finally made by postoperative pathology, with positive immunohistochemical S-100 staining and negative pancytokeratin. The patient has been followed for 6 mo so far, with no tumor recurrence detected. CONCLUSION: This case highlights the biological feature and differential diagnosis of urinary bladder GCT at the pathological and molecular levels. Transurethral resection of the bladder tumor and partial cystectomy are recommended in most urinary bladder GCT cases, while radical cystectomy is recommended in malignant cases.

Aptamer Probes Labeled with Lanthanide-Doped Carbon Nanodots Permit Dual-Modal Fluorescence and Mass Cytometric Imaging.

High-dimensional imaging mass cytometry (IMC) enables simultaneous quantification of over 35 biomarkers on one tissue section. However, its limited resolution and ultralow acquisition speed remain major issues for general clinical application. Meanwhile, conventional immunofluorescence microscopy (IFM) allows sub-micrometer resolution and rapid identification of the region of interest (ROI), but only operates with low multiplicity. Herein, a series of lanthanide-doped blue-, green-, and red-fluorescent carbon nanodots (namely, B-Cdots(Ln1 ), G-Cdots(Ln2 ), and R-Cdots(Ln3 )) as fluorescence and mass dual-modal tags are developed. Coupled with aptamers, B-Cdots(159 Tb)-A10-3.2, G-Cdots(165 Ho)-AS1411, and R-Cdots(169 Tm)-SYL3C dual-functional aptamer probes, which are then multiplexed with commercially available Maxpar metal-tagged antibodies for analyzing clinical formalin-fixed, paraffin-embedded (FFPE) prostatic adenocarcinoma (PaC) tissue, are further synthesized. The rapid identification of ROI with IFM using fluorescence signals and subsequent multiplexed detection of in situ ROI with IMC using the same tissue section is demonstrated. Dual-modal probes save up to 90% IMC blind scanning time for a standard 3.5 mm × 3.5 mm overall image. Meanwhile, the IFM provides refined details and topological spatial distributions for the functional proteins at optical resolution, which compensates for the low resolution of the IMC imaging.

CRISPR/Cas12a Powered DNA Framework-Supported Electrochemical Biosensing Platform for Ultrasensitive Nucleic Acid Analysis.

Nucleic acid analysis using ultrasensitive and simple methods is critically important for the early-stage diagnosis and treatment of diseases. The CRISPR/Cas proteins, guided by a single-stranded RNA have shown incredible capability for sequence-specific targeting and detection. Herein, in order to improve and expand the application of CRISPR/Cas technology to the electrochemical interface-based nucleic acids analysis, the authors develop a CRISPR/Cas12a powered DNA framework-supported electrochemical biosensing platform via the cis and trans cleavage of Cas12a on the heterogeneous carbon interface (the existing publications which commonly adopted trans-cleavage). Their solid-liquid interface is first immobilized by 3D tetrahedral framework nucleic acids (FNAs) with specific DNA recognition probe. Based on the recognition of the complementary target through protospacer adjacent motif (PAM) confirmation and CRISPR-derived RNA (crRNA) matching, the easily formed Cas12a/crRNA duplex can get access to the interface, and the cis and trans cleavage of Cas12a can be easily activated. In combination with the enzyme catalyzed reaction, they achieved an ultralow limit of detection (LOD) of 100 fm in HPV-16 detection without pre-amplification. Furthermore, the platform is compatible with a spike-in human serum sample and has superior stability. Thus, their reported platform offers a practical, versatile, and amplification-free toolbox for ultrasensitive nucleic acid analysis.

From "feeling" to "seeing": modification of the percutaneous peritoneal dialysis catheter insertion with an optical puncture system.

PURPOSE: Blind insertion limits the application of percutaneous peritoneal dialysis (PD) catheter placement. In this study, we first described the use of an optical puncture system in the PD catheter insertion, and investigated the feasibility and advantages of this modified technique. METHODS: This retrospective study included 65 patients with chronic kidney disease stage 5 (CKD5) who received ultrasound-guided percutaneous PD catheter insertion with or without optical puncture system assistance between June 2018 and July 2019. The patients' characteristics as well as the surgical outcomes and complications were compared between the modified group and the routine percutaneous insertion group. RESULTS: Twenty-five patients underwent optical puncture system assistant insertion, whereas 40 patients received routine percutaneous insertion. More patients had previous abdominal surgical histories in the modified group than those in the routine group (24.0% vs. 5.0%, p = 0.047). The time of accessing to the abdominal cavity was significantly shorter in the modified group (median [IQR]; 1.1 min [0.8-1.3] vs. 5.0 min [4.0-6.0]; p < 0.001). Meanwhile, the time of the whole procedure was also significantly shorter in the modified group (median [IQR]; 26.0 min [25.0-29.0] vs. 33.0 min [29.0-35.0]; p < 0.001). None of the patient in the modified group, while two patients (5.0%) in the routine group converted to open procedure. There were no significant differences in the short and long postoperative complications between the two groups. CONCLUSIONS: The operation of ultrasound-guided PD catheter placement with the optical puncture system is easy, safe, fast and accurate, whereby the PD catheter can be implanted percutaneously and visually under local anesthesia with minimal procedure-related complications. The visible puncture of the optical puncture system may facilitate ultrasound-guided percutaneous PD catheter insertion in patients with obesity and previous abdominal surgeries.

Antitumor effects and mechanisms of CpG ODN combined with attenuated Salmonella-delivered siRNAs against PD-1.

Numerous studies have focused on the treatment of melanoma, but the current therapies for melanoma have limited therapeutic effects. To find a more effective therapy for melanoma, we combined artificially designed CpG ODN (cytosine-phosphate-guanine oligodeoxynucleotides) and siRNAs (small-interfering ribonucleic acids) targeting PD-1 (programmed cell death protein 1), which were delivered by attenuated Salmonella to treat melanoma in mice, and explored the underlying antitumor mechanisms. We found that mice receiving the combination therapy had the smallest tumor size and the longest survival time. The possible mechanisms underlying this phenomenon include pathways mediated by cyclin D1, p-STAT3 (phosphorylated signal transducers and activators of transcription protein 3), MMP2 (matrix metallopeptidase 2) and cleaved caspase 3, since after treatment, the expression of cyclin D1, p-STAT3, and MMP2 decreased but that of cleaved caspase 3 increased; additional mechanisms include increases in the recruitment of immune cells to tumor sites and in the number of immune cells in mouse spleens and the upregulation of TNF-α (tumor necrosis factor) and IL-6 (interleukin 6). We demonstrated that the combination therapy composed of CpG ODN and PD-1-siRNA delivered by attenuated Salmonella exhibited a strong ability to inhibit melanoma and improve the antitumor immune responses of tumor-bearing mice.