A nanomedicine composed of polymer-ss-DOX and polymer-Ce6 prodrugs with monoclonal antibody targeting effect for anti-tumor chemo-photodynamic synergetic therapy.

Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity and uncontrolled drug release due to their lack of targeting. To improve the bioavailability of drugs and reduce side effects, we have developed a mixed micelle of nanomedicine composed of two prodrugs with surface modified monoclonal antibody for cancer therapy. In this system, Nimotuzumab was used as targeting ligands of the mixed micelles (named as DCMMs) that is composed of polymer-doxorubicin prodrug (abbreviated as PEG-b-P(GMA-ss-DOX)) and maleimide polyethylene glycol-chlorin e6 (abbreviated as Mal-PEG-Ce6). The mixed micelles modified with Nimotuzumab (named as NTZ-DCMMs) bind to overexpressed EGFR receptors on Hepatoma-22 (H22) cells. Disulfide bonds in PEG-b-P(GMA-ss-DOX) are disrupted in tumor microenvironment, inducing the reduction-responsive release of DOX and leading to tumor cell apoptosis. Simultaneously, Chlorin e6 (Ce6) produced plenty of singlet oxygen (1O2) under laser irradiation to kill tumor cells. In vivo biological distribution and antineoplastic effect experiments demonstrate that NTZ-DCMMs enhanced drug enrichment at tumor sites through targeting function of antibody, dramatically suppressing tumor growth and mitigating cardiotoxicity of drugs. All results prove that NTZ-DCMMs have the ability to actively target H22 cells and quickly respond to tumor microenvironment, which is expected to become an intelligent and multifunctional drug delivery carrier for efficient chemotherapy and photodynamic therapy of hepatoma. STATEMENT OF SIGNIFICANCE: Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity due to their lack of targeting. Therefore, it's necessary to develop effective, targeted, and collaborative treatment strategies. We construct a mixed micelle of nanomedicine based on two polymer prodrugs and modified with monoclonal antibody on surface for cancer therapy. Under the tumor cell microenvironment, the disulfide bonds of polymer-ss-DOX were broken, effectively triggering DOX release. The photosensitizer Ce6 could generate a large amount of ROS under light, which synergistically promotes tumor cell apoptosis. By coupling antibodies to the hydrophilic segments of polymer micelles, drugs can be specifically delivered. Compared with monotherapy, the combination of chemotherapy and photodynamic therapy can significantly enhance the therapeutic effect of liver cancer.

A CD326 monoclonal antibody modified core cross-linked curcumin-polyphosphoester prodrug for targeted delivery and cancer treatment.

Stimuli-responsive cross-linked micelles (SCMs) are ideal nanocarriers for anti-cancer drugs. Compared with non-cross-linked micelles, SCMs exhibit superior structural stability. At the same time, the introduction of an environmentally sensitive crosslinker into a drug delivery system allows SCMs to respond to single or multiple stimuli in the tumor microenvironment, which can minimize drug leakage during the blood circulation process. In this study, curcumin (CUR) was modified as the hydrophobic core crosslinker by utilizing the bisphenol structure, and redox sensitive disulfide bonds were introduced to prepare the glutathione (GSH) stimulated responsive core crosslinker (abbreviated as N3-ss-CUR-ss-N3). In addition, amphiphilic polymer APEG-b-PBYP was prepared through the ring opening reaction, and reacted with the crosslinker through the "click" reaction. After being dispersed in the aqueous phase, core cross-linked nanoparticles (CCL NPs) were obtained. Finally, monoclonal antibody CD326 (mAb-CD326) was reduced and coupled to the hydrophilic chain ends to obtain the nanoparticles with surface modified antibodies (R-mAb-CD326@CCL NPs) for further enhancing targeted drug delivery. The structures of the polymer and crosslinker were characterized by 1H NMR, UV-Vis, FT-IR, and GPC. The morphology, size and stability of CCL NPs and R-mAb-CD326@CCL NPs were investigated by DLS and TEM. The in vitro drug release behavior of CCL NPs was also studied. The results showed that the CCL NPs exhibited reduction-responsiveness and were able to release the original drug CUR under 10 mM GSH conditions. Additionally, the CCL NPs exhibited excellent stability in both the simulated body fluid environment and organic solvents. Especially, R-mAb-CD326@CCL NPs can actively target tumor cells and showed better therapeutic efficacy in in vivo experiments with a tumor suppression rate of 78.7%. This work provides a new idea for the design of nano-drugs targeting breast cancer.

Albumin pre-opsonized membrane-active iPep nanomedicine potentiates chemo to immunotherapy of cancer.

Chemotherapy-conjugated immunotherapy in clinical oncology conceptually resembles the combined effects of cytoreduction and immunostimulation in membrane targeted cell killings mediated by pore-forming proteins or host defense peptides. Of the similar concept, targeting cancer cell membrane using membrane active peptides is a hopeful therapeutic modality but had long been hindered from in vivo application. Here we report an enabling strategy of pre-opsonizing a membrane penetrating Ir-complexed octa-arginine peptide (iPep) with serum albumin via intrinsic amphipathicity-driven bimodal interactions into nanoparticles (NP). We found that NP triggered stress-mediated 4T1 cell oncosis which induced potent immunological activation, surpassing several well-known immunogenic medicines. Vested with albumin-enhanced in vivo tumor targeting specificity and pharmacokinetic properties, NP showed combined chemo to immunotherapies of s. c. tumors in mice, with decreased percentages of MDSC, Treg, M2-like macrophage and improved infiltration of CTLs in tumor site, caused complete regression of 4T1 and CT26 tumors, outperforming clinical medicines. In a challenging orthotopic breast cancer model, boost i. v. injections of NP acted as in situ tumor vaccine that drastically enhanced 4T1-specific cellular and humoral immunities to reverse disease progression. Thus, with combined effects of direct cytoreduction, immune activation and tumor vaccine, iPep-NP presents the promise and potential of a new modality of cancer medicine.

Liquid metal microspheres with an eddy-thermal effect for magnetic hyperthermia-enhanced cancer embolization-immunotherapy.

Patients with hepatocellular carcinoma (HCC) display poor prognosis because HCC involves a high rate of metastasis and regrowth. Herein, we present an effective strategy to treat HCC using magnetic hyperthermia therapy (MHT)-enhanced cancer immunotherapy combined with transcatheter arterial embolization (TAE). Uniform liquid metal microspheres (LM MSs) obtained by microfluidic technology with powerful eddy-thermal effects could be used as both MHT and TAE agents for effective cancer therapy. The eddy-thermal effect of LM MSs demonstrated effective MHT, whereas LM MS-induced MHT boosted the immune system, promoted immune cell infiltration, and further stimulated powerful immune responses to suppress the growth of distant tumors, together with immune checkpoint blockade therapy. Furthermore, LM MS-lipiodol dispersion displayed excellent efficacy of the combined MHT-TAE in the orthotopic rabbit liver cancer model. Our work not only highlighted that LM MSs could act as effective MHT agents to achieve MHT-enhanced immunotherapy but also presented the significant promise of combining MHT with TAE for the efficient treatment of large orthotopic liver tumors.

Tailoring the d-band electronic structure of deficient LaMn0.3Co0.7O3-δ perovskite nanofibers for boosting oxygen electrocatalysis in Zn-Air batteries.

The development and design of efficient bifunctional electrocatalysts towards oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are crucial for rechargeable Zinc-air batteries (ZABs). Optimizing the d-band structure of active metal center in perovskite oxides is an effective method to enhance ORR/OER activity by accelerating the rate-determining step. Herein, we report a deficient method to optimize the d-band structure of Co ions in LaMn0.3Co0.7O3-δ (LMCO-2) perovskite nanofibers, which regulates the mutual effect between B-site Co ions and reactive oxygen intermediates. It is proved by experiment and theoretical calculation that the d-band center (Md) of transition metal ions in LMCO-2 is moved up and the electron filling number of eg orbital in B site is 1.01, thus leading to the reduction of Gibbs free energy required for ORR rate-determining step (OH*→H2O*) to 0.22 eV and promoting reaction proceeds. In this manner, LMCO-2 showed good bifunctional oxygen electrocatalytic activity, with a half-wave potential of 0.71 V vs. RHE. Furthermore, the high specific capacity of 811.54 mAh g-1 and power density of 326.56 mW cm-2 were obtained by using LMCO-2 as the cathode catalyst for ZABs. This study proved the feasibility of d-band structure regulation to enhance the electrocatalytic activity of perovskite oxides.

Dextran-doxorubicin prodrug nanoparticles conjugated with CD147 monoclonal antibody for targeted drug delivery in hepatoma therapy.

Antibody-drug conjugates (ADCs) are a class of tumor cell-targeting drugs that have developed rapidly in recent years. From the perspective of further improving ADC targeting and developing natural macromolecules as drug carriers, it is still challenging and necessary to try new targeted drug delivery modalities. In this study, we have developed an antibody-modified prodrug nanoparticle based on biomacromolecule dextran (DEX) to delivery antitumour drug doxorubicin (DOX). Firstly, oxidized dextran (ODEX) and DOX were bonded to yield ODEX-DOX via Schiff base reaction, which can self-assemble into nanoparticles (NPs) carrying some aldehyde groups. Subsequently, the amino groups of CD147 monoclonal antibody were bound to the aldehyde groups on the surface of ODEX-DOX NPs, resulting in acid-responsive and antibody-modified CD147-ODEX-DOX NPs with relatively small particle size and high DOX loading. FT-IR, UV-Vis, HPLC, and 1H NMR were used to demonstrate the successful synthesis of polymer prodrug ODEX-DOX NPs and antibody-modified nanomedicine CD147-ODEX-DOX NPs. Dynamic light scattering (DLS) was used to evaluate the stability and the pH responsiveness of ODEX-DOX NPs in different media and tumour microenvironment. The in vitro total release content of DOX reached approximately 70% in PB 5.0 buffer solution after 103 h. Furthermore, the in vivo antitumour efficacy and biodistribution experiments confirmed that CD147-ODEX-DOX NPs could significantly inhibit the growth of HepG2 tumour. All of the results indicate that this acid-sensitive nanomedicine has higher safety and targeting effects. It promises to be an ideal strategy for future targeted drug delivery systems and anticancer therapies.

A hybrid hydrogel constructed using drug loaded mesoporous silica and multiple response copolymer as an intelligent dressing for wound healing of diabetic foot ulcers.

Traditional wound dressings have poor mechanical properties and a single function, which cannot achieve rapid healing of diabetic wounds in a unique physiological microenvironment. In order to develop multifunctional hydrogel dressings with appropriate biological activity to accelerate wound healing and obtain better clinical therapeutic effects, herein we report a hybrid system based on drug loaded mesoporous silica and injectable polymer hydrogels mixed with hypoglycemic drug metformin (Met) as a dressing for diabetic wounds. Firstly, a copolymer with the phenylboronic acid group in the side group, poly(acrylamide-co-dimethylaminopropylacrylamide-co-methacrylamidophenylboronic acid) (abbreviated as PB), was prepared. PB was mixed with polyvinyl alcohol (PVA) to obtain an injectable hydrogel (named PP) with pH/glucose dual responsiveness, which was formed through the combination of the phenylborate group of PB and o-diol of PVA. In another reaction, polydopamine-modified mesoporous silica nanoparticles (MSN@PDA) were prepared and used to adsorb antibiotic tetracycline hydrochloride (TH) to obtain drug-loaded MSN@PDA-TH nanoparticles. Subsequently, the hybrid hydrogel dressing (abbreviated as PP/MSN@PDA-TH/Met) was obtained by mixing PB, PVA, Met and MSN@PDA-TH. The self-healing, rheological and adhesive properties of the hybrid hydrogel were characterized. The results show that the hydrogel dressing has good physical properties. Met and TH were released in vitro in different pH media and glucose environments. The results show that the hydrogel dressing has dual responsiveness towards pH and glucose, and can continuously release metformin and tetracycline, which is conducive to accelerating wound healing. The antimicrobial activity, ROS clearance ability and biocompatibility of the hydrogel dressing were evaluated. The results indicate that the hydrogel dressing was multifunctional. Finally, a full-thickness wound repair model of diabetic mice induced by streptozotocin (STZ) was established. The hybrid hydrogel dressing was applied to the wound surface of mice. The wound healing testing on diabetic mice confirmed that the wound covered with the hybrid hydrogel dressing was completely healed with the formation of the new skin and hair within 9 days to 12 days. Histological analysis indicates that, compared to the PBS control, the hydrogel dressing did not cause significant inflammation in the wound, and a large number of blood vessels, glands and hair follicles appeared. This study provides a good strategy for multi-drug synergistic treatment of diabetic foot ulcers.

CD163 Monoclonal Antibody Modified Polymer Prodrug Nanoparticles for Targeting Tumor-Associated Macrophages (TAMs) to Enhance Anti-Tumor Effects.

Tumor-associated macrophages (TAMs)-based immunotherapy is a promising strategy. Since TAMs are mainly composed of M2-type macrophages, they have a promoting effect on tumor growth, invasion, and metastasis. M2-type macrophages contain a specific receptor CD163 on their surface, providing a prerequisite for active targeting to TAMs. In this study, we prepared CD163 monoclonal antibody modified doxorubicin-polymer prodrug nanoparticles (abbreviated as mAb-CD163-PDNPs) with pH responsiveness and targeted delivery. First, DOX was bonded with the aldehyde group of a copolymer by Schiff base reaction to form an amphiphilic polymer prodrug, which could self-assemble into nanoparticles in the aqueous solution. Then, mAb-CD163-PDNPs were generated through a "Click" reaction between the azide group on the surface of the prodrug nanoparticles and dibenzocyclocytyl-coupled CD163 monoclonal antibody (mAb-CD163-DBCO). The structure and assembly morphology of the prodrug and nanoparticles were characterized by 1H NMR, MALDI-TOF MS, FT-IR UV-vis spectroscopy, and dynamic light scattering (DLS). In vitro drug release behavior, cytotoxicity, and cell uptake were also investigated. The results show that the prodrug nanoparticles have regular morphology and stable structure, especially mAb-CD163-PDNPs, which can actively target TAMs at tumor sites, respond to the acidic environment in tumor cells, and release drugs. While depleting TAMs, mAb-CD163-PDNPs can actively enrich drugs at the tumor site and have a strong inhibitory effect on TAMs and tumor cells. The result of the in vivo test also shows a good therapeutic effect, with a tumor inhibition rate of 81%. This strategy of delivering anticancer drugs in TAMs provides a new way to develop targeted drugs for immunotherapy of malignant tumors.

PD-1 monoclonal antibodies enhance the cryoablation-induced antitumor immune response: a breast cancer murine model research.

BACKGROUND: It has been demonstrated that cryoablation (Cryo) causes specific T-cell immune responses in the body; however, it is not sufficient to prevent tumor recurrence and metastasis. In this report, we evaluated changes in the tumor immune microenvironment (TIME) in distant tumor tissues after Cryo and investigated the immunosuppressive mechanisms that limit the efficacy of Cryo. METHODS: Bilateral mammary tumor models were established in mice, and we first observed the dynamic changes in immune cells and cytokines at different time points after Cryo. Then, we confirmed that the upregulation of PD-1 and PD-L1 signaling in the contralateral tumor tissue was closely related to the immunosuppressive state in the TIME at the later stage after Cryo. Finally, we also evaluated the synergistic antitumor effects of Cryo combined with PD-1 monoclonal antibody (mAb) in the treatment of breast cancer (BC) mouse. RESULTS: We found that Cryo can stimulate the body's immune response, but it also induces immunosuppression. The elevated PD-1/PD-L1 expression in distant tumor tissues at the later stage after Cryo was closely related to the immunosuppressive state in the TIME but also created the conditions for Cryo combined with PD-1 mAb for BC mouse treatment. Cryo + PD-1 mAb could improve the immunosuppressive state of tumors and enhance the Cryo-induced immune response, thus exerting a synergistic antitumor effect. CONCLUSIONS: The PD-1/PD-L1 axis plays an important role in suppressing Cryo-induced antitumor immune responses. This study provides a theoretical basis for Cryo combined with PD-1 mAb therapy in clinical BC patients.

Functional cRGD-Conjugated Polymer Prodrug for Targeted Drug Delivery to Liver Cancer Cells.

To overcome the limitation of conventional nanodrugs in tumor targeting efficiency, coupling targeting ligands to polymeric nanoparticles can enhance the specific binding of nanodrugs to tumors. Cyclo(Arg-Gly-Asp-d-Phe-Lys) (abbreviated as c(RGDfK)) peptide has been widely adopted due to its high affinity to the tumor marker αvß3 integrin receptor. In this study, we develop a cRGD peptide-conjugated camptothecin (CPT) prodrug, which enables self-assembly of nanoparticles for precise targeting and enrichment in tumor tissue. We first synthesized a camptothecin derivative (CPT-ss-N3) with a reduction-sensitive bond and simultaneously modified PEG to obtain cRGD-PEG-N3. After ring-opening polymerization of the 2-(but-3-yn-1-yolxy)-2-oxo-1,3,2-dioxaphospholane (BYP), an amphiphilic polymeric prodrug, referred to as cRGD-PEG-g-(PBYP-ss-CPT), was obtained via copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The self-assembly in buffer solution of the cRGD-functional prodrug was studied through DLS and TEM. The in vitro drug release behavior of cRGD-PEG-g-(PBYP-ss-CPT) nanoparticles was investigated. The results show that the nanoparticles are reduction-responsive and the bonded CPT can be released. Endocytosis and MTT assays demonstrate that the cRGD-conjugated prodrug has better affinity for tumor cells, accumulates more intracellularly, and is therefore, more effective. The in vivo drug metabolism studies show that nanoparticles greatly prolong the retention time in circulation. By monitoring drug distribution in tumor and in various tissues, we find that free CPT can be rapidly metabolized, resulting in low accumulation in all tissues. However, cRGD-PEG-g-(PBYP-ss-CPT) nanoparticles accumulate in tumor tissues in higher amounts than PEG-g-(PBYP-ss-CPT) nanoparticles, except for the inevitable capture by the liver. This indicates that the nanomedicine with cRGD has a certain targeting property, which can improve drug delivery efficiency.

A Bifunctional Chemomechanics Strategy To Suppress Electrochemo-Mechanical Failure of Ni-Rich Cathodes for All-Solid-State Lithium Batteries.

Electrochemo-mechanical failure of Ni-rich cathodes leads to rapid performance degradation, and thus hinders their practical implementation in all-solid-state lithium batteries (ASSLBs). To solve this problem, herein, we propose a bifunctional chemomechanics strategy by protecting polycrystalline LiNi0.6Co0.2Mn0.2O2 (NCM) cathodes using a high-mechanical-strength fast ionic conductor LiZr2(PO4)3 (LZP) coating layer. The coating layer's synergistic effect between mechanical strength and electrochemical stability is studied in Li6PS5Cl (LPSCl)-based ASSLBs for the first time. Using finite element method (FEM) simulations and various characterization techniques, we demonstrate that the robust and stable LZP (Young's modulus 140.7 GPa, electrochemical stability window >5 V) coating layer mitigates the volume change and particle disintegration of polycrystalline NCM and electrochemical decomposition of LPSCl on the LPSCl/NCM interface. As a result, the LZP-modified ASSLBs display remarkably improved reversible capacity, cycle life, and rate performance. The synergy of mechanical and electrochemical properties of the coating layer will provide valuable guidance for the development of high-energy-density ASSLBs.

Healing Diabetic Ulcers with MoO3-X Nanodots Possessing Intrinsic ROS-Scavenging and Bacteria-Killing Capacities.

Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO3-X ) for healing the DUs are reported. The ROS scavenging ability of MoO3-X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO3-X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO3-X nanodots for diabetic wound therapy.

Embedding Co2P nanoparticles in Cu doping carbon fibers for Zn-air batteries and supercapacitors.

Developing highly efficient and non-precious materials for Zn-air batteries (ZABs) and supercapacitors (SCs) are still crucial and challenging. Herein, electronic reconfiguration and introducing conductive carbon-based materials are simultaneously conducted to enhance the ZABs and SCs performance of Co2P. We develop a simple and efficient electrospinning technology followed by carbonization process to synthesize embedding Co2P nanoparticles in Cu doping carbon nanofibers (Cu-Co2P/CNFs). As a result, the 7% Cu-Co2P/CNFs presents high oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activity (half-wave potential of 0.792 V for ORR, an overpotential of 360 mV for OER). The ZABs exhibit a power density of 230 mW cm-2and excellent discharge-charge stability of 80 h. In addition, the 7% Cu-Co2P/CNFs show the specific capacitance of 558 F g-1at 1 A g-1. Moreover, the 7% Cu-Co2P/CNFs//CNFs asymmetric supercapacitor was assembled applying 7% Cu-Co2P/CNFs electrode and pure CNFs, which exhibits a high energy density (25.9 Wh kg-1), exceptional power density (217.5 kW kg-1) and excellent cycle stability (96.6% retention after 10 000 cycles). This work may provide an effective way to prepared Co2P based materials for ZABs and SCs applications.

Long noncoding RNA VPS9D1-AS1 promotes esophageal squamous cell carcinoma progression via the Wnt/ß-catenin signaling pathway.

The VPS9D1 antisense RNA1 (VPS9D1-AS1, lncRNA MYU) can act as an oncogene or an antioncogene in different malignancies. In the present study, we demonstrated that VPS9D1-AS1 is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and assessed its biological function and clinical prognosis. RNA-sequencing was conducted in four pairs of ESCC tissues and normal adjacent tissues (NATs). Compared with controls, lncRNA VPS9D1-AS1 was highly expressed in ESCC tissues, cell lines and plasma. VPS9D1-AS1 upregulation significantly correlated with the histopathological grade and clinical stage of ESCC. Analyses revealed poor prognosis in ESCC patients with high VPS9D1-AS1 expression. VPS9D1-AS1 knockdown led to the inhibition of tumor proliferation, migration, and invasion in vivo and vitro. VPS9D1-AS1 silencing downregulated the Wnt/ß-catenin signaling pathways by acting on key proteins such as ß-catenin and c-Myc. However, the expressions of these proteins increased after the addition of pathway agonist CT99021. Therefore, taken together VPS9D1-AS1 is highly expressed in ESCC and its expression can lead to poor prognosis. In conclusion, this study suggested that VPS9D1-AS1 acts as a vital part in facilitating ESCC progression and can be a potential biomarker for the diagnosis of patients with ESCC.

Glucose-Sensitive Core-Cross-Linked Nanoparticles Constructed with Polyphosphoester Diblock Copolymer for Controlling Insulin Delivery.

This work aims to construct biocompatible, biodegradable core-cross-linked and insulin-loaded nanoparticles which are sensitive to glucose and release insulin via cleavage of the nanoparticles in a high-concentration blood glucose environment. First, a polyphosphoester-based diblock copolymer (PBYP-g-Gluc)-b-PEEP was prepared via ring-opening copolymerization (ROP) and the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in which PBYP and PEEP represent the polymer segments from 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane and 2-ethoxy-2-oxo-1,3,2-dioxaphospholane, respectively, and Gluc comes from 2-azidoethyl-ß-d-glucopyranoside (Gluc-N3) that grafted with PBYP. The structure and molecular weight of the copolymer were characterized by 1H NMR, 31P NMR, GPC, FT-IR, and UV-vis measurements. The amphiphilic copolymer could self-assemble into core-shell uncore-cross-linked nanoparticles (UCCL NPs) in aqueous solutions and form core-cross-linked nanoparticles (CCL NPs) after adding cross-linking agent adipoylamidophenylboronic acid (AAPBA). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to study the self-assembly behavior of the two kinds of NPs and the effect of different Gluc group contents on the size of NPs further to verify the stability and glucose sensitivity of CCL NPs. The ability of NPs to load fluorescein isothiocyanate-labeled insulin (FITC-insulin) and their glucose-triggered release behavior were detected by a fluorescence spectrophotometer. The results of methyl thiazolyl tetrazolium (MTT) assay and hemolysis activity experiments showed that the CCL NPs had good biocompatibility. An in vivo hypoglycemic study has shown that FITC-insulin-loaded CCL NPs could reduce blood glucose and have a protective effect on hypoglycemia. This research provides a new method for constructing biodegradable and glucose-sensitive core-cross-linked nanomedicine carriers for controlled insulin release.

Perioperative and Postoperative Complications of Supraclavicular, Ultrasound-Guided, Totally Implantable Venous Access Port via the Brachiocephalic Vein in Adult Patients: A Retrospective Multicentre Study.

PURPOSE: The totally implantable venous access port (TIVAP) provides patients with safe, effective and long-term convenient venous access for the administration of medications such as chemotherapy drugs. The implantation and long-term use of TIVAP are related to thrombosis, infection and other complications. In this study, the medical records of multicentre patients were collected, and the perioperative and postoperative complications were retrospectively analysed to objectively evaluate the safety of the implantation of supraclavicular, ultrasound-guided TIVAP via the brachiocephalic vein (BCV). PATIENTS AND METHODS: We retrospectively analysed the clinical data of 433 adult patients who had undergone ultrasound-guided TIVAP implantation via the BCV at four hospitals in China from March 2018 to May 2019. The success rates of the first puncture, operation time, and perioperative and postoperative complications were analysed. RESULTS: All the TIVAPs were implanted successfully (100%). The average TIVAP carrying time was 318.15 ±44.22 days (range: 38-502 days) for a total of 197,694 catheter days. The success rate of the first puncture was 94.92% (411/433), and the average operation time was 29.66 ±7.45 min (range: 18-60 min). The perioperative complications included arterial puncture in 4 patients and pneumothorax in 1 patient. The incidence of postoperative complications was 5.08% (22/433), including poor incision healing (n = 2), catheter-related infection (n = 3), port infection (n = 6), thrombosis (n = 2) and fibrin sheath formation (n = 8). Another patient had infusion disturbance 2 days after the operation, and chest X-ray showed bending at the connection between the catheter and port. No other serious complications occurred, such as catheter rupture and drug leakage. The total incidence of complications was 6.24% (27/433). CONCLUSION: This study showed excellent tolerance of supraclavicular, ultrasound-guided BCV puncture to implant TIVAP and a low incidence of complications. As a safe and effective method of TIVAP implantation, it can provide a new choice for clinicians.

Perioperative and Postoperative Complications of Ultrasound-Guided Totally Implantable Venous Access Ports via the Brachiocephalic Vein in Patients with Cancer: A Prospective Study.

Objectives: To evaluate the safety and efficacy of ultrasound (US)-guided totally implantable venous access ports (TIVAPs) via the right brachiocephalic vein (BCV) or the left BCV approach. Methods: Patients requiring TIVAP for chemotherapy were included in the study. US-guided TIVAPs via BCV were used for patients from July 2018 to December 2018. General information about the patients (sex, age, and diagnosis), side (right or left), surgical procedures and complications were recorded. Results: A total of 107 TIVAPs in 107 patients (ages 38-73 years) were included, 75 via the right BCV and 32 via the left BCV. All of the patients underwent successful surgery. The BCV was successfully punctured on the first attempt in 99 patients (92.52%). Two attempts were needed in 6 patients (5.61%), and three attempts were necessary in 2 patients (1.87%). The mean operation time was 29 ± 5 min (range: 24 to 38 min). No serious complications occurred during the surgery, except the formation of a local haematoma in 1 case after artery puncture. During the follow-up period of 12 months, the incidence of long-term complications was 3.74% (4/107), including 2 cases of catheter-related infection and 2 cases of fibrin sheath formation. No serious complications such as catheter malposition or rupture were found. Conclusion: US-guided TIVAP via the BCV offers an alternative for adults with good needle guidance and a low rate of perioperative and postoperative complications.

Application of ultrasound-guided intranodal lymphangiography and embolisation in cancer patients with postoperative lymphatic leakage.

BACKGROUND: Traumatic lymphatic leakage is a rare but potentially life-threatening complication. The purpose of this study was to introduce ultrasound-guided intranodal lymphangiography and embolisation techniques for postoperative lymphatic leakage in patients with cancer. METHODS: From January 2018 through June 2020, seven cancer patients (three males, four females, aged 59-75 years [mean 67.57 ± 6.11 years]) developed lymphatic leakage after abdominal or pelvic surgery, with drainage volumes ranging from 550 to 1200 mL per day. The procedure and follow-up of ultrasound-guided intranodal lymphangiography and embolisation were recorded. This study retrospectively analysed the technical success rate, operative time, length of hospital stay, clinical efficacy, and complications. RESULTS: The operation was technically successful in all patients. Angiography revealed leakage, and embolisation was performed in all seven patients (7/7, 100%). The operative time of angiography and embolisation was 41 to 68 min, with an average time of 53.29 ± 10.27 min. The mean length of stay was 3.51 ± 1.13 days. Lymph node embolisation was clinically successful in five patients (5/7, 71.43%), who had a significant reduction in or disappearance of chylous ascites. The other two patients received surgical treatment 2 weeks later due to poor results after embolisation. All patients were followed for 2 weeks. No serious complications or only minor complications were found in all the patients. CONCLUSIONS: Ultrasound-guided intranodal lymphangiography and embolisation were well tolerated by the patients, who experienced a low incidence of complications. Early intervention is recommended for cancer patients with postoperative lymphatic leakage.

Safety study of Folfox-HAIC in relieving bed restriction.

Objective: To investigate the safety of relieving bed restriction in hepatic arterial infusion chemotherapy (HAIC) and its effects on patient comfort. Methods: A prospective study was conducted. Patients with malignant liver tumors, who met the enrollment criteria, were randomly divided into experimental and control groups. During HAIC treatment, the patients in the experimental group, who were not confined to bed and could get out of bed, used electronic injection pumps to infuse chemotherapy drugs. The patients in the control group, who were strictly confined to bed and prohibited from getting out of bed, used infusion pumps to infuse chemotherapy drugs. The complications of the two groups were observed. The Christenson standard improved method was used to evaluate the bleeding and hematoma of limbs on the operation side. The Kolcaba General Comfort Questionnaire (GCQ) and Barthel Index (BI) were used to evaluate the two groups. Results: Ninety patients with malignant liver tumors were enrolled, including 53 with primary liver cancer and 37 with colorectal liver metastasis. There were 70 males and 20 females, aged 41-81 years old, with an average age of 61.6 â€‹± â€‹9.248 years old. There were 60 patients in the experimental group and 30 patients in the control group. All patients underwent HAIC. The study showed that, during the treatment period, there were 3 cases of postoperative puncture point hematoma formation in the two groups, including 2 cases in the experimental group (2/60, 3.3%) and 1 case in the control group (1/30, 3.3%). The difference was not statistically significant (p â€‹> â€‹0.05). There were 5 cases of postoperative puncture point bleeding, including 4 cases in the experimental group (4/60, 6.7%) and 1 case in the control group (1/30, 3.3%), and the difference was not statistically significant (p â€‹> â€‹0.05). A total of 23 cases, with 6 cases in the experimental group (6/60, 10%) and 17 cases in the control group (17/30, 56.7%), complained of back pain after the operation, and the difference was statistically significant (p â€‹< â€‹0.05). Twenty-one cases complained of poor defecation after the operation, including 10 cases in the experimental group (10/60, 16.7%) and 11 cases in the control group (11/30, 36.7%). The difference was statistically significant (p â€‹< â€‹0.05). During the period of infusion chemotherapy, the two groups of patients had there was a significant difference between the two groups in terms of comfort status (GCQ) (88.78 â€‹± â€‹6.705, 78.47 â€‹± â€‹9.519, p â€‹< â€‹0.001) and self-care ability (BI) (74.25 â€‹± â€‹9.152, 66.83 â€‹± â€‹6.628, p â€‹< â€‹0.001). Conclusion: During HAIC treatment, getting out of bed is safe and reliable and can increase the patients' comfort and self-care ability. Hence, it merits clinical application.

In-situ visualization of the space-charge-layer effect on interfacial lithium-ion transport in all-solid-state batteries.

The space charge layer (SCL) is generally considered one of the origins of the sluggish interfacial lithium-ion transport in all-solid-state lithium-ion batteries (ASSLIBs). However, in-situ visualization of the SCL effect on the interfacial lithium-ion transport in sulfide-based ASSLIBs is still a great challenge. Here, we directly observe the electrode/electrolyte interface lithium-ion accumulation resulting from the SCL by investigating the net-charge-density distribution across the high-voltage LiCoO2/argyrodite Li6PS5Cl interface using the in-situ differential phase contrast scanning transmission electron microscopy (DPC-STEM) technique. Moreover, we further demonstrate a built-in electric field and chemical potential coupling strategy to reduce the SCL formation and boost lithium-ion transport across the electrode/electrolyte interface by the in-situ DPC-STEM technique and finite element method simulations. Our findings will strikingly advance the fundamental scientific understanding of the SCL mechanism in ASSLIBs and shed light on rational electrode/electrolyte interface design for high-rate performance ASSLIBs.