The rapid emergence of antibiotic resistance in pathogenic microbes is becoming an imminent global public health problem. Local application of antibiotics might be a solution. In local application, materials need to act as the drug delivery system. The drug delivery system should be biodegradable and prolonged antibacterial effect should be provided to satisfy clinical demand. Hydrogel is a promising material for local antibacterial application. Hydrogel refers to a kind of biomaterial synthesized by a water-soluble natural polymer or a synthesized polymer, which turns into gel according to the change in different signals such as temperature, ionic strength, pH, ultraviolet exposure etc. Because of its high hydrophilicity, unique three-dimensional network, fine biocompatibility and cell adhesion, hydrogel is one of the suitable biomaterials for drug delivery in antimicrobial areas. In this review, studies from the past 5 years were reviewed, and several types of antimicrobial hydrogels according to different ingredients, different preparations, different antimicrobial mechanisms, different antimicrobial agents they contained and different applications, were summarized. The hydrogels loaded with metal nanoparticles as a potential method to solve antibiotic resistance were highlighted. Finally, future prospects of development and application of antimicrobial hydrogels are suggested.

In recent years, in situ chemotherapy mediated by biodegradable polymer platforms has attracted increased attention. Herein, an advanced drug delivery system, combretastatin A-4 (CA4) and docetaxel (DTX)-loaded microsphere embedded in injectable thermosensitive polypeptide hydrogel (i.e., hydrogel-microsphere (Gel-MP) construct), was reported for sequential release of drugs with different mechanisms to treat osteosarcoma synergistically. The Gel-MP construct showed sequential biodegradability and excellent biocompatibility. CA4 was preferentially released from hydrogel with faster degradation to disturb the vascular structure of the tumor and reduce the exchange of nutrients between the tumor and surrounding tissues, which created interstitial space in the tissue for DTX penetration to inhibit tumor cell proliferation. The in vivo treatment with Gel/CA4-MP/DTX efficiently suppressed the growth of mouse K7 osteosarcoma compared to other formulations. More importantly, by systematical study of histopathology and immunohistochemistry, the Gel-MP construct can significantly upregulate antiproliferation effect and reduce toxicity of drugs. Therefore, this injectable and locally sequential delivery system has a bright prospect in clinical application of in situ synergistic chemotherapy.

Titanium alloy prostheses have been widely used for the treatment of orthopedic diseases, in which the interconnected porosity and appropriate pore size are crucial for the osseointegration capacity. Three-dimensional (3D) printing technology provides an efficient method to construct prosthesis scaffolds with controllable internal and surface structure, but printing high-porosity (>60%) scaffolds with pore diameters below 300 μm as implants structures has not yet been studied. In this work, four types of titanium alloy scaffolds with interconnected porosity more than 70% were successfully prepared by selective laser melting (SLM). The actual mean pore sizes of cylindrical scaffolds are 542, 366, 202, and 134 μm. Through the in vitro characterization of the scaffolds, in vivo experiments, and mechanical experiments, it is concluded that as the scaffold pore diameter decreases, the titanium alloy scaffold with diameter of 202 μm has the strongest osseointegration ability and is also the most stable one with the surrounding bone. These findings provide a reference for the clinical pore-size design of porous scaffolds with optimal bone growth stability on the surface of the titanium alloy implant.

TMEM16A, a calcium-activated chloride channel (CaCC), is highly amplified and expressed in human cancers and is involved in the growth and metastasis of some malignancies. Inhibition of TMEM16A represents a novel pharmaceutical approach for the treatment of cancers and metastases. The purpose of this study is to identify a new TMEM16A inhibitor, investigate the effects of this inhibitor on the proliferation and metastasis of TMEM16A-amplified SW620 cells, and to elucidate the underlying molecular mechanism in vitro. We identified a novel small-molecule TMEM16A inhibitor dehydroandrographolide (DP). By using patch clamp electrophysiology, we showed that DP inhibited TMEM16A chloride currents in Fisher rat thyroid (FRT) cells that were transfected stably with human TMEM16A and in TMEM16A-overexpressed SW620 cells but did not alter cystic fibrosis transmembrane conductance regulator (CFTR) chloride currents. Further functional studies showed that DP suppressed the proliferation of SW620 cells in a dose- and time-dependent manner using MTT assays. Moreover, DP significantly inhibited migration and invasion of SW620 cells as detected by wound-healing and transwell assays. Further mechanistic study demonstrated that knockdown of human TMEM16A decreased the inhibitory effect of DP on the proliferation of SW620 cells and that TMEM16A-dependent cells (SW620 and HCT116) were more sensitive to DP than TMEM16A-independent cells (SW480 and HCT8). In addition, we found that treatment of SW620 cells with DP led to a decrease in TMEM16A protein levels but had no effect on TMEM16A mRNA levels. The current work reveals that DP, a novel TMEM16A inhibitor, exerts its anticancer activity on SW620 cells partly through a TMEM16A-dependent mechanism, which may introduce a new targeting approach for an antitumour therapy in TMEM16A-amplified cancers.

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Different indices have been used to reflect, or monitor the ionospheric scintillation, e.g. the detrended carrier phase, δφ, S4,  the rate of change of the total electron content index (ROTI), as well as the ionosphere‐free linear combination (IFLC) of two carrier phases. However, few studies have been performed to investigate the refractive and diffractive contributions to these indices, especially during geomagnetic storms. In this study, we analyze the high-resolution (50 Hz) phase and amplitude measurements from four high-latitude stations in Svalbard, Norway during the geomagnetic storm on 7-8 September 2017. Our results show that at high latitudes, the high-pass filter with a standard cutoff frequency of 0.1 Hz sometimes cannot effectively remove the refraction driven phase variations, especially during the geomagnetic storm, leading to a remaining refraction contribution to the detrended carrier phase and δφ when scintillation happens. In the meanwhile, as ROTI is sensitive to the TEC gradients, regardless of small- or large-scale ionospheric structures, both refraction and diffraction effects can cause visible fluctuations of ROTI. For most of the scintillation events, the phase indices (including detrended carrier phase, δφ, and ROTI), IFLC and S4 show consistent fluctuations, indicating that diffraction usually occurs simultaneously with refraction during scintillation. One interesting feature is that although the IFLC and S4 are thought to be both related to the diffraction effect, they do not always show simultaneous correspondence during scintillations. The IFLC is enhanced during the geomagnetic storm, while such a feature is not seen in S4. We suggest that the enhanced IFLC during geomagnetic storm is caused by the increased high-frequency phase power, which should be related to the enhanced density of small-scale irregularities during storm periods.

Introduction:Periprosthetic femoral fractures (PFF) around tumor prosthesis of knee are stubborn problems for surgeons, huge bone defect and inappropriate biomechanics of the revision implant design can be disaster for reconstruction. With the development of three-dimensional (3D) printing technology, surgeons participate more in precise preoperative design and simulation for treatment of such fractures. In this study we explored an accurate and feasible way to restore normal anatomy and function of the knee joint with 3D printing technology.Case presentation:Rationale: This report explored an accurate and feasible way to treat PFF around tumor knee prosthesis in a 32 years old women with 3D printing technology, which restored normal anatomy and function of the knee joint. Patient concerns: Pain in left thigh lasted for 10 months after resection of left femoral chondroma and knee joint replacement four years ago. Diagnoses: periprosthetic femoral fractures (PFF) around tumor knee prosthesis.Interventions:CT images of the patient were collected and reconstructed. Parameters of bilateral femurs were virtually sliced and measured. Novel femoral stem and nail paths were specially designed by doctors according to these parameters. The prosthetic femoral stem components and navigator were customized by engineers according to the doctor's design. The residual femoral resin model, customized components and navigator were printed with Stereo Lithography Apparatus 3D printer. The shape-preconcerted allograft bone was selected as patch for the bone defect before operation with the printed bone model. All the steps were simulated preoperatively with the models printed, and then the operation was carried out. Outcomes: The operation was successfully performed. The postoperative x-ray image, MSTS93 scores were examined and the function restoration sustained well in the follow-up period from 1 month to 27 months. Lessons: 3D printing and medical interaction are key points in complex PFF cases.Conclusion:As for PFF of the complex tumor of knee, preoperative design and simulation with 3D printing technology may provide more accurate and effective operative outcome than traditional methods, which might be considered as a method suitable for popularization in complex and severe cases.

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