Non-Invasive Detection of Early-Stage Fatty Liver Disease via an On-Skin Impedance Sensor and Attention-Based Deep Learning.

Early-stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non-invasive and cost-effective detection method for early-stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on-skin sensor with low electrode-skin contact impedance for early-stage NAFLD detection is fabricated. A method is developed to synthesize platinum nanoparticles and reduced graphene quantum dots onto the on-skin sensor to reduce electrode-skin contact impedance by increasing double-layer capacitance, thereby enhancing detection accuracy. Furthermore, an attention-based deep learning algorithm is introduced to differentiate impedance signals associated with early-stage NAFLD in high-fat-diet-fed low-density lipoprotein receptor knockout (Ldlr-/-) mice compared to healthy controls. The integration of an adhesive, soft on-skin sensor with low electrode-skin contact impedance and the attention-based deep learning algorithm significantly enhances the detection accuracy for early-stage NAFLD, achieving a rate above 97.5% with an area under the receiver operating characteristic curve (AUC) of 1.0. The findings present a non-invasive approach for early-stage NAFLD detection and display a strategy for improved early detection through on-skin electronics and deep learning.

Multifunctional Microneedle Patches via Direct Ink Drawing of Nanocomposite Inks for Personalized Transdermal Drug Delivery.

Additive manufacturing, commonly known as 3D printing, allows decentralized drug fabrication of orally administered tablets. Microneedles are comparatively favorable for self-administered transdermal drug delivery with improved absorption and bioavailability. Due to the cross-scale geometric characteristics, 3D-printed microneedles face a significant trade-off between the feature resolution and production speed in conventional layer-wise deposition sequences. In this study, we introduce an economical and scalable direct ink drawing strategy to create drug-loaded microneedles. A freestanding microneedle is efficiently generated upon each pneumatic extrusion and controlled drawing process. Sharp tips of ∼5 µm are formed with submillimeter nozzles, representing 2 orders of magnitude improved resolution. As the key enabler of this fabrication strategy, the yield-stress fluid inks are formulated by simply filling silica nanoparticles into regular polymer solutions. The approach is compatible with various microneedles based on dissolvable, biodegradable, and nondegradable polymers. Various matrices are readily adopted to adjust the release behaviors of the drug-loaded microneedles. Successful fabrication of multifunctional patches with heterogeneously integrated microneedles allows the treatment of melanoma via synergistic photothermal therapy and combination chemotherapy. The personalized patches are designed for cancer severity to achieve high therapeutic efficacy with minimal side effects. The direct ink drawing reported here provides a facile and low-cost fabrication strategy for multifunctional microneedle patches for self-administering transdermal drug delivery.

A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy.

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Polymeric Phthalocyanine-Based Nanosensitizers for Enhanced Photodynamic and Sonodynamic Therapies.

Photodynamic therapy and sonodynamic therapy are two highly promising modalities for cancer treatment. The latter holds an additional advantage in deep-tumor therapy owing to the deep penetration of the ultrasonic radiation. The therapeutic efficacy depends highly on the photo/ultrasound-responsive properties of the sensitizers as well as their tumor-localization property and pharmacokinetics. A novel nanosensitizer system based on a polymeric phthalocyanine (pPC-TK) is reported herein in which the phthalocyanine units are connected with cleavable thioketal linkers. Such polymer could self-assemble in water forming nanoparticles with a hydrodynamic diameter of 48 nm. The degradable and flexible thioketal linkers could effectively inhibit the π-π stacking of the phthalocyanine units, rendering the resulting nanoparticles an efficient generator of reactive oxygen species upon light or ultrasonic irradiation. The nanosensitizer could be internalized into cancer cells readily, inducing cell death by efficient photodynamic and sonodynamic effects. The potency is significantly higher than that of the monomeric phthalocyanine (PC-4COOH). The nanosensitizer could also effectively inhibit the growth of tumor in liver tumor-bearing mice by these two therapies without causing noticeable side effects. More importantly, it could also retard the growth of a deep-located orthotopic liver tumor in vivo by sonodynamic therapy.

Secondary Structure in Overcoming Photosensitizers' Aggregation: α-Helical Polypeptides for Enhanced Photodynamic Therapy.

Aggregation caused quenching (ACQ) effect can severely inhibit the application of hydrophobic photosensitizers (PSs) bearing planar and rigid structures. Most of the reported cases utilized random-coiled polymers for the in vivo delivery of PSs, which would inevitably aggravate ACQ effect due to the flexible chains. In this work, the role of polymers' secondary structures (especially α-helical conformation) in overcoming the PSs' aggregation is systemically investigated based on the design of α-helical polypeptides bearing tetraphenylporphyrin (TPP) side chains. Atomistic molecular dynamics simulation, fluorescence quantum yield, and reactive oxygen species (ROS) generation yield are evaluated to demonstrate that α-helical polypeptide backbones can significantly boost both fluorescence quantum yield and ROS by suppressing the π-π stacking interaction between TPP units. The enhanced in vitro and in vivo phototoxicity for helical polypeptides also reveal functions of secondary structures in inhibiting ACQ and improving the membrane activity. Successful in vivo photodynamic therapy (PDT) results in mice bearing H22 tumors showed great potentials for further clinical applications.

Management of Fused Anterior Teeth: Review and Clinical Report.

The phenomenon of fusion is a type of tooth dysplasia, but few studies have systematically described the treatment of this kind of abnormality. This paper summarizes the treatment methods for fused teeth and classifies the management schemes according to whether the pulp is fused. Then, the treatment for a patient with bilateral anterior tooth fusion is reported. After orthodontic treatment, porcelain veneers were used to restore the normal shape and aesthetic appearance of the anterior teeth.

The hsa_circRNA_102049 mediates the sorafenib sensitivity of hepatocellular carcinoma cells by regulating Reelin gene expression.

A growing body of research has illuminated that non-coding RNAs (ncRNAs) plays an important role in the development of drug resistance in hepatocellular carcinoma (HCC) cells. The expression profiles of differential expressed genes (DEGs) and ncRNAs related to the sorafenib resistance in HCC cells were analyzed according to the Gene Expression Omnibus (GEO) dataSets and The Cancer Genome Atlas (TCGA) datasets. Bioinformatics technology was used to construct the interaction network of DEGs and ncRNAs. Cell transfection, dual-luciferase reporter assay, Western blot, cell counting kit-8 (CCK-8), flow cytometry and quantitative real-time polymerase chain reaction(qRT-PCR) were used to study the mechanism of sorafenib resistance in HepG2 cells and Huh-7 cells. The expression of reelin (RELN) and secretagogin (SCGN) were the only down-regulated in sorafenib-resistant HCC cells. The results showed that RELN gene demethylation reversed the cytotoxic of sorafenib on HepG2 cells and Huh-7 cells. Hsa_circRNA_102049 over-expression promoted the sensitivity of HepG2 cells and Huh-7 cells to sorafenib, hsa_circRNA_102049 up-regulated the expression of RELN gene by sponging hsa-miR-214-3p. The resistance to sorafenib in RELN knockout HepG2 cells and Huh-7 cells could be reverted by has-circRNA_102049. These findings support targeting of hsa_circRNA_102049 and RELN in sorafenib-treated HCC cells as a novel intervention, which is expected to overcome sorafenib resistance of HCC cells.

Robot-assisted technique vs conventional freehand technique in spine surgery: A meta-analysis.

BACKGROUND: The impact of robot-assisted techniques versus conventional freehand techniques in terms of the accuracy of pedicle screw placement remains conflicting. This meta-analysis was performed to evaluate this relationship. METHODS: A systematic literature search up to July 2020 was performed and 15 studies were detected with 6041 pedicle screw placements with 2748 of them were using robot-assisted techniques and 3293 were conventional freehand techniques. They reported relationships between robot-assisted techniques and conventional freehand techniques in pedicle screw placement. Odds ratio (OR) or Mean differences (MD) with 95% confidence intervals (CIs) was calculated comparing the robot-assisted techniques to conventional freehand techniques in pedicle screw placement risks using the dichotomous and continuous method with a random or fixed-effect model. RESULTS: Robot-assisted techniques had a significantly higher screw position grade A in Gertzbein-Robbins classification of the screw placement accuracy (OR, 2.43; 95% CI, 1.66-3.54, P < .001); shorter postoperative stay (MD, -0.67; 95% CI, -1.16 to -0.19, P < .001); lower intraoperative blood loss (MD, -91.64; 95% CI, -152.44 to -30.83, P = .003); fewer intraoperative radiation dose (MD, -23.52; 95% CI, -40.12 to -6.0.93, P = .005); and low proximal facet violations (MD, 0.08; 95% CI, 0.03-0.20, P < .001) compared with conventional freehand techniques. However, no significant difference was found between robot-assisted techniques and conventional freehand techniques in surgical time (OR, 11.71; 95% CI, 03.27-26.70, P = .13); visual analogue scale scores (MD, -0.15; 95% CI, -0.54 to 0.23, P = .44); and Oswestry disability index scores (MD, 0.21; 95% CI, -5.09-5.51, P = .94). CONCLUSIONS: The extent of the improvement with robot-assisted techniques in screw position grade A in Gertzbein-Robbins classification of the screw placement accuracy, postoperative stay, intraoperative blood loss, intraoperative radiation dose, and proximal facet violations was significantly better than conventional freehand techniques. This relationship forces us to recommend robot-assisted techniques for pedicle screw placement to avoid any possible negative postoperative results.

Comparison of total disc arthroplasty and fusion in treatment of lumbar disc disease: A cohort study protocol.

BACKGROUND: In recent years, the clinical efficacy of spinal fusion (SF) or total disc arthroplasty (TDA) in the treatment of the degenerative lumbar disc disease is still controversial. The objective of this retrospective clinical trial was to investigate whether TDA was superior to the SF in the complication rates and clinical outcome scores. METHODS: This retrospective research was based on the Strengthening the Reporting of Observational studies in Epidemiology checklist. Internal clinical data sets for 2014 to 2018 were acquired and consolidated with the approval of the Institutional Review Committee of Shaoxing Hospital of Zhejiang University. Inclusion criteria in this present research included: low back pain without or with the leg pain for more than one year; failure of conservative treatment planned for more than three months; age was 25 to 60 years old; followed up for at least one year. The main outcome measure was disability and pain measured via the Norwegian version of Oswestry disability index 2.0. The other clinical outcomes included Short-Form Health Survey, reoperations, duration of surgery, complications, hospital stay length, as well as the blood loss. The significance was set at 0.05 level with the confidence intervals of 95%. The software package of SPSS (version 21.0; SPSS Inc, Chicago, IL, USA) was applied for all the analyses of statistics. RESULTS: The null hypothesis is that there is no significant difference in outcomes between TDA and SF in the treatment of degenerative lumbar disc disease. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5847).

Efficacy of bone marrow stem cells combined with core decompression in the treatment of osteonecrosis of the femoral head: A PRISMA-compliant meta-analysis.

BACKGROUND: This study used the meta-analytic approach to assess the safety and treatment efficacy of bone marrow stem cells (BMSCs) with core decompression (CD) for osteonecrosis of the femoral head (ONFH) based on randomized controlled trials (RCTs). METHODS: Electronic database of PubMed, Embase, Google Scholar, China National Knowledge Infrastructure (CNKI), and Wanfang database was searched up to December 26, 2019 for relevant RCTs about combined utilization of BMSCs and CD versus CD alone for ONFH. Gray literature sources were also searched. We conducted a meta-analysis following the guidelines of the Cochrane Reviewer's Handbook. Two independent reviewers performed the data extraction and assessed study quality. Our outcomes included the Harris hip scores (HHS) at 12 months, HHS at 24 months, necrotic area of femoral head, conversion to total hip arthroplasty (THA), visual analog pain scale at final follow-up, and adverse effects. The meta-analysis was performed with Stata 12.0. RESULTS: A total of 15 published studies with 688 patients fulfilled the requirements of inclusion criteria. Across all populations, participants in combined utilization of BMSCs group showed a statistical significance with higher HHS at 12 months (standard mean difference [SMD] 0.53, 95% confidence interval [CI] 0.29-0.77) and 24 months (SMD 0.57, 95% CI 0.36-0.77). Similarly, participants in combined utilization of BMSCs group had more advantages in reducing necrotic area of femoral head (SMD -1.05, 95% CI -1.73 to -0.38) and the rate of conversion to THA (risk ratio [RR] = 0.53, 95% CI 0.38-0.74, P = .000). No significant differences were identified regarding postoperative adverse effects postoperatively (RR = 1.03, 95% CI 0.64-1.67, P = .893). CONCLUSION: Compared with CD treated alone in the treatment of ONFH, combined utilization of CD and autologous BMSCs implantation has a better pain relief and clinical outcomes and can delay the collapse of the femoral head more effectively.