Quma Tongluo Prescription in the Treatment of Chronic Oxaliplatin Related Peripheral Neuropathy: A Single-Center, Open, Randomized Controlled Study.

Objective: To observe the effect of oral Quma Tongluo decoction on oxaliplatin-related chronic peripheral neuropathy. Methods: A total of 64 patients who met the inclusion criteria were randomly divided into an experimental group and a control group, with 32 cases in each group. The experimental group took Quma Tongluo decoction granules orally (2 times a day, 1 package each time, morning and evening after meals), and the control group took mecobalamin tablets orally (1 tablet each time, 3 times a day, after meals). After 4 weeks of treatment, the quantitative score of chronic peripheral neuropathy severity, a quantitative score of numbness, a quantitative score of pain, a chemotherapeutic peripheral neurotoxicity score, comprehensive neuropathy score, peripheral neurotoxicity grade, KPS score, and neuropathy area range score were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences between the two groups in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score (P > .05). After 4 weeks of treatment, there were significant differences in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score between the two groups (P < .05). There was no significant difference in pain quantification score and KPS score between the two groups before and after treatment (P > .05). The total effective rate of Quma Tongluo decoction in the treatment of oxaliplatin-related chronic peripheral neuropathy was higher than that of mecobalamin (87.1% > 20.6%), and no obvious adverse reactions such as Gastrointestinal reactions and allergic reactions were observed.One patient in the experimental group had diarrhea, the incidence of adverse reactions was about 3.2%, and the control group had no adverse reactions. Conclusions: Quma Tongluo decoction can effectively treat oxaliplatin-related chronic peripheral neuropathy, reduce the symptoms while reducing the scope of symptoms, and has no obvious adverse reactions in clinical practice, with good safety.

Bioactivities of essential oil extracted from Elsholtzia densa Benth. And its main components against Tribolium castaneum eggs and pupae.

This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, ß-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of ß-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of ß-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of ß-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of ß-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, ß-caryophyllene, and limonene.

Bioactivities and Synergistic Effect of Elsholtzia ciliata Essential Oil and Its Main Components against Lasioderma serricorne.

Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.

Sensitivity of Pharmacokinetics to Differences in the Particle Size Distribution for Formulations of Locally Acting Mometasone Furoate Suspension-Based Nasal Sprays.

To assess bioequivalence of locally acting suspension-based nasal sprays, the U.S. FDA currently recommends a weight-of-evidence approach. In addition to in vitro and human pharmacokinetic (PK) studies, this includes a comparative clinical endpoint study to ensure equivalent bioavailability of the active pharmaceutical ingredient (API) at the site of action. The present study aimed to assess, within an in vitro/in vivo correlation paradigm, whether PK studies and dissolution kinetics are sensitive to differences in drug particle size for a locally acting suspension-based nasal spray product. Two investigational suspension-based nasal formulations of mometasone furoate (MF-I and MF-II; delivered dose: 180 µg) differed in API particle size and were compared in a single-center, double-blind, single-dose, randomized, two-way crossover PK study in 44 healthy subjects with oral charcoal block. Morphology-directed Raman spectroscopy yielded volume median diameters of 3.17 µm for MF-I and 5.50 µm for MF-II, and dissolution studies showed that MF-II had a slower dissolution profile than MF-I. The formulation with larger API particles (MF-II) showed a 45% smaller Cmax and 45% smaller AUC0-inf compared to those of MF-I. Systemic bioavailability of MF-I (2.20%) and MF-II (1.18%) correlated well with the dissolution kinetics, with the faster dissolving formulation yielding the higher bioavailability. This agreement between pharmacokinetics and dissolution kinetics cross-validated both methods and supported their use in assessing potential differences in slowly dissolving suspension-based nasal spray products.

Mechanisms of cancer cell death induction by paclitaxel: an updated review.

Chemoresistance of cancer cells is a major problem in treating cancer. Knowledge of how cancer cells may die or resist cancer drugs is critical to providing certain strategies to overcome tumour resistance to treatment. Paclitaxel is known as a chemotherapy drug that can suppress the proliferation of cancer cells by inducing cell cycle arrest and induction of mitotic catastrophe. However, today, it is well known that paclitaxel can induce multiple kinds of cell death in cancers. Besides the induction of mitotic catastrophe that occurs during mitosis, paclitaxel has been shown to induce the expression of several pro-apoptosis mediators. It also can modulate the activity of anti-apoptosis mediators. However, certain cell-killing mechanisms such as senescence and autophagy can increase resistance to paclitaxel. This review focuses on the mechanisms of cell death, including apoptosis, mitotic catastrophe, senescence, autophagic cell death, pyroptosis, etc., following paclitaxel treatment. In addition, mechanisms of resistance to cell death due to exposure to paclitaxel and the use of combinations to overcome drug resistance will be discussed.

High-temperature magnetic skyrmions in BiCrX3 (X = Se and Te) monolayers.

Two-dimensional magnetic van der Waals materials provide a fertile platform for the design and control of topological spin textures such as skyrmions. However, despite studies reporting skyrmions in many 2D magnetic systems, those of the hosting van der Waals materials remain limited. Here, via first-principles calculations and Monte Carlo simulations, we propose BiCrX3 as a new family of materials for hosting skyrmions. Due to the large SOC of the X atom and intrinsic inversion asymmetry, an inherent large DMI occurs in all systems, enabling intriguing Néel-type skyrmions. Furthermore, upon applying a moderate magnetic field, isolated skyrmions and skyrmion lattices emerge in our systems, and are robust within a relatively wide temperature range.

N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways.

BACKGROUND: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP. METHODS: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level was scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression. RESULTS: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG. CONCLUSIONS: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

MicroRNAs and angiogenesis: a new era for the management of colorectal cancer.

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20-22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.

Receptor activity-modifying protein 1 regulates the phenotypic expression of BMSCs via the Hippo/Yap pathway.

Receptor activity-modifying protein 1 (RAMP1) might be a critical regulator during bone wound healing. However, the roles and mechanisms of RAMP1 in osteogenesis remain unclear. Here, we aimed to elucidate the role of RAMP1 and explore the effects of Yes-associated protein 1 (Yap1), an effector of the Hippo/Yap pathway, in this process. We used a RAMP1 overexpression lentiviral system in bone marrow mesenchymal stem cells (BMSCs), which enhanced RAMP1 expression in an effective, appropriate, and sustained manner. Alkaline phosphatase (ALP) activity assays and alizarin red staining showed that RAMP1 promoted osteogenic differentiation of BMSCs after calcitonin gene-related peptide (CGRP) treatment (10 -8 mol/L). Moreover, real-time polymerase chain reaction and Western blot analysis indicated that RAMP1 upregulated the expression of osteogenic phenotypic markers (ALP, runt-related transcription factor 2, osteopontin; p < 0.05). To further uncover the mechanism of RAMP1 in osteogenic differentiation, we used verteporfin (10 -7 mol/L) to block Yap1. Notably, verteporfin impaired RAMP1-induced osteogenesis. Taken together, our findings confirmed that RAMP1 is a key mediator of bone regeneration and indicate that RAMP1 promotes CGRP-induced osteogenic differentiation of BMSCs via regulation of the Hippo/Yap pathway.

Corpus Callosotomy for Patients With Intractable Seizures: An Insight Into the Rapid Relapse.

It is well known that corpus callosotomy (CC) can bring a favorable seizure control outcome for disabling generalized seizures, but the complete remission rate achieved by CC is rarely reported, and the postoperative relapse pattern is still not clear. In this study, the authors reviewed patients with medically refractory epilepsy who were suffering disabling seizures, including drop attacks, generalized tonic-clonic seizures (GTCS), tonic seizures, atonic seizures, atypical absences, and complex partial seizures. The patients underwent anterior two third or complete CC in our hospital. Seizure control outcome was evaluated postoperatively at 2 weeks, 1 month, 3 months, 6 months, thereafter, at yearly intervals. Seizure-free or >90% reduction was considered to be satisfactory. There were 14 patients with mean age 11.00 ±â€Š6.34 at surgery. Of all the patients, 6 patients underwent anterior two third CC, and the other 8 patients underwent complete CC. All the patients were postoperatively followed up for at least 1 year. Four patients (28.57%) were free of all seizure types in the first year after surgery. Among the 9 patients with follow-up longer than 3 years, 2 patients (22.22%) were free of all seizure types. In the first 3 months after surgery, more than half of the seizure free patients (55.56%) relapsed with the same seizure types as preoperatively. Although after that, there was only 1 patient relapsed. Of all the seizure types, CC achieved the most favorable seizure outcome in drop attacks. In conclusion, CC could achieve complete seizure remission in a small portion of selected candidates. Exploration of the relapse mechanism will contribute to improve the seizure outcome following CC.

Notable mucosal immune responses induced in the intestine of zebrafish (Danio rerio) bath-vaccinated with a live attenuated Vibrio anguillarum vaccine.

Live attenuated vaccine is one of the efficient vaccine candidates in aquaculture, which can be easily delivered to fish via bath-vaccination. An outstanding advantage of bath-vaccination is that vaccine delivery is through the same route as that utilized by many fish pathogens, generating specific mucosal immune responses. In this work, we investigated the mucosal immune responses induced by a live attenuated Vibrio anguillarum vaccine in zebrafish via bath-vaccination. Bacteria proliferated rapidly in 3 h after vaccination and maintained at a high level until 6 h in the intestine. Besides, bacteria persisted in the intestine for a longer time whereas decreased rapidly in the skin and gills. Moreover, a significant up-regulation of TLR5 triggering a MyD88-dependent signaling pathway was observed in the intestine, which implied that flagella were the crucial antigenic component of the live attenuated vaccine. And macrophages and neutrophils showed active responses participating in antigen recognition and sampling after vaccination. Furthermore, an inflammation was observed with plenty of lymphocytes in the intestine at 24 h post vaccination but eliminated within 7 days. In conclusion, the live attenuated V. anguillarum vaccine induced notable mucosal immune responses in the intestine which could be used as a mucosal vaccine vector in the future.

Largazole pharmacokinetics in rats by LC-MS/MS.

A highly sensitive and specific LC-MS/MS method for the quantitation of largazole thiol, the active species of the marine-derived preclinical histone deacetylase inhibitor, largazole (prodrug), was developed and validated. Largazole thiol was extracted with ethyl acetate from human or rat plasma along with the internal standard, harmine. Samples were separated on an Onyx Monolithic C18 column by a stepwise gradient elution with 0.1% formic acid in methanol and 0.1% aqueous formic acid employing multiple reaction monitoring (MRM) detection. Linear calibration curves were obtained in the range of 12.5-400 ng/mL with 200 µL of human plasma. The overall intra-day precision was from 3.87% to 12.6%, and the inter-day precision was from 7.12% to 9.8%. The accuracy at low, medium and high concentrations ranged from 101.55% to 105.84%. Plasma protein bindings of largazole thiol in human and rat plasma as determined by an ultrafiltration method were 90.13% and 77.14%, respectively. Plasma drug concentrations were measured by this LC-MS/MS method. The pharmacokinetics of largazole thiol in rats was studied following i.v. administration at 10 mg/kg and found to follow a two-compartment model. Largazole thiol was rapidly eliminated from systemic circulation within 2 h. The established LC-MS/MS method is suitable for the analysis of largazole thiol in human plasma, as well.

Photoelectrons Sequentially Regulate Antibacterial Activity and Osseointegration of Titanium Implants.

Titanium implants are widely used ; however, implantation occasionally fails due to infections during the surgery or poor osseointegration after the surgery. To solve the problem, an intelligent functional surface on titanium implant that can sequentially eradicate bacteria biofilm at the initial period and promote osseointegration at the late period of post-surgery time is designed. Such surfaces can be excited by near infrared light (NIR), with rare earth nanoparticles to upconvert the NIR light to visible range and adsorb by Au nanoparticles, supported by titanium oxide porous film on titanium implants. Under NIR irradiation, the implant converts the energy of phonon to hot electrons and lattice vibrations, while the former flows directly to the contact substance or partially reacts with the surrounding to generate reactive oxygen species, and the latter leads to the local temperature increase. The biofilm or microbes on the implant surface can be eradicated by NIR treatment in vitro and in vivo. Additionally, the surface exhibits superior biocompatibility for cell survival, adhesion, proliferation, and osteogenic differentiation, which provides the foundation for osseointegration. In vivo implantation experiments demonstrate osseointegration is also promoted. This work thus demonstrates NIR-generated electrons can sequentially eradicate biofilms and regulate the osteogenic process, providing new solutions to fabricate efficient implant surfaces.

Ion-incorporated titanium implants for staged regulation of antibacterial activity and immunoregulation-mediated osteogenesis.

Antibacterial properties and osteogenic activity are considered as two crucial factors for the initial healing and long-term survivability of orthopedic implants. For decades, various drug-loaded implants to enhance biological activities have been investigated extensively. More importantly, to control the drug release timing is equally significant due to the sequential biological processes after implantation. Hence, developing a staged regulation system on the titanium surface is practically significant. Here, we prepared TiO2 nanotubes (TiO2 NTs) on the titanium surface by anodization, followed by the incorporation of zinc (Zn) and strontium (Sr) sequentially through a hydrothermal process. Surface characterization confirmed the successful fabrication of Zn and Sr-incorporated TiO2 NTs (Zn-Sr/TiO2) on the titanium surface. The ion release results exhibited the differential release characteristic of Zn and Sr, which meant the early-stage release of Zn and the long-term release of Sr. It was exactly in accord with  the biological process after implantation, laying the basis of staged regulation after implantation. Zn-Sr/TiO2 showed favorable anti-early infection properties both in vitro and in vivo. Its inhibition effect on bacterial biofilm formation was attributed to the resistance against bacteria's initial adhesion and the killing effect on planktonic bacteria. Additionally, the release of Sr could alleviate infection-induced damage via immunoregulation. The biocompatibility and osteogenic activity mediated by M2 macrophage activation were confirmed with in vitro and in vivo studies. Therefore, it exhibited great potential in staged regulation for antibacterial activity in the early stage and the M2 activation-mediated osteogenic activity in the late stage. The staged regulation process was based on the differential release of Zn and Sr to achieve the early antibacterial effect and the long-term immune-induced osteogenic activity, to prevent implant-related infection and achieve better osseointegration. These two kinds of ions played their roles synergistically and complement mutually. This work is expected to provide an innovative idea for realizing sequential regulation after implantation.

Regulation of the upconversion effect to promote the removal of biofilms on a titanium surface via photoelectrons.

Biofilms on public devices and medical instruments are harmful. Hence, it is of great importance to fabricate antibacterial surfaces. In this work, we target the preparation of an antibacterial surface excited by near-infrared light via the coating of rare earth nanoparticles (RE NPs) on a titanium surface. The upconverted luminescence is absorbed by gold nanoparticles (Au NPs, absorber) to produce hot electrons and reactive oxygen species to eliminate the biofilms. The key parameters in tuning the upconversion effect to eliminate the biofilms are systematically investigated, which include the ratios of the sensitizer, activator, and matrix in the RE NPs, or the absorber Au NPs. The regulated RE NPs exhibit an upconversion quantum yield of 3.5%. Under illumination, photogenerated electrons flow through the surface to bacteria, such as E. coli, which disrupt the breath chain and eventually lead to the death of bacteria. The mild increase of the local temperature has an impact on the elimination of biofilms on the surface to a certain degree as well. Such a configuration on the surface of titanium exhibits a high reproducibility on the removal of biofilms and is functional after the penetration of light using soft tissue. This work thus provides a novel direction in the application of upconversion materials to be used in the fabrication of antibacterial surfaces.

The engineering of defect-modified boron nitride ribbons: an effective adsorbent to rapid capture for tetracycline.

Antibiotics, the persistent organic pollutants, have brought serious pollution to the aquatic environment. Therefore, it is necessary to select rapid adsorbents to remove them from their long-term threat. Herein, the introduction of defects in BN was employed to enhance its surface chemical activity for rapid capture of tetracycline via hydrothermal and calcination methods. The defect content in BN can be controlled by adjusting the volume ratio of ethanol to water. Among them, when the volume ratio of H2O/ethanol is 4/1 (BN-3), BN-3 has the most N defects at 33%, which increases the adsorption rate of h-BN for TC and promotes the adsorption capacity to 302.15 mg g-1, which is due to the introduction of nitrogen defects significantly regulates the electronic structure of BN. The corresponding theoretical calculations confirm that BN with N defects decreases the absorption energy of BN for TC. Additionally, the adsorption removal rate of tetracycline still reached 95.5% after 5 cycles of TC adsorption by BN-3, indicating that the defect-modified BN has good reusability and is beneficial for its use in pollutant adsorption.

Mechanism of Preventing Recurrence of Stage II-III Colorectal Cancer Metastasis with Immuno-inflammatory and Hypoxic Microenvironment by a Four Ingredients Chinese Herbal Formula: A Bioinformatics and Network Pharmacology Analysis.

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.

Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonite-gentamicin sulfate with drug release pathways.

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.

X-ray CT image denoising with MINF: A modularized iterative network framework for data from multiple dose levels.

In clinical applications, multi-dose scan protocols will cause the noise levels of computed tomography (CT) images to fluctuate widely. The popular low-dose CT (LDCT) denoising network outputs denoised images through an end-to-end mapping between an LDCT image and its corresponding ground truth. The limitation of this method is that the reduced noise level of the image may not meet the diagnostic needs of doctors. To establish a denoising model adapted to the multi-noise levels robustness, we proposed a novel and efficient modularized iterative network framework (MINF) to learn the feature of the original LDCT and the outputs of the previous modules, which can be reused in each following module. The proposed network can achieve the goal of gradual denoising, outputting clinical images with different denoising levels, and providing the reviewing physicians with increased confidence in their diagnosis. Moreover, a multi-scale convolutional neural network (MCNN) module is designed to extract as much feature information as possible during the network's training. Extensive experiments on public and private clinical datasets were carried out, and comparisons with several state-of-the-art methods show that the proposed method can achieve satisfactory results for noise suppression of LDCT images. In further comparisons with modularized adaptive processing neural network (MAP-NN), the proposed network shows superior step-by-step or gradual denoising performance. Considering the high quality of gradual denoising results, the proposed method can obtain satisfactory performance in terms of image contrast and detail protection as the level of denoising increases, which shows its potential to be suitable for a multi-dose levels denoising task.

Collision of Commonality and Personalization: Better Understanding of the Periosteum.

The periosteum is quite essential for bone repair. The excellent osteogenic properties of periosteal tissue make it a popular choice for accelerated osteogenesis in tissue engineering. With advances in research and technology, renewed attention has been paid to the periosteum. Recent studies have shown that the complexity of the periosteum is not only limited to histological features but also includes genetic and phenotypic features. In addition, the periosteum is proved to be quite site-specific in many ways. This brings challenges to the selection of periosteal donor sites. Limited understanding of the periosteum sets up barriers to developing optimal tissue regeneration strategies. A better understanding of periosteum could lead to better applications. Therefore, we reviewed the histological structure, gene expression, and function of the periosteum from both the commonality and personalization. It aims to discuss some obscure issues and untapped potential of periosteum and artificial periosteum in the application, where further theoretical research is needed. Overall, the site-specificity of the periosteum needs to be fully considered in future applications. However, significant further work is needed in relevant clinical trials to promote the further development of artificial periosteum.