Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells.

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.

Mutagenic Effect during Combined Exposure to Ionizing and Non-Ionizing Electromagnetic Radiation.

Using the method of dominant lethal mutations, we assessed the frequency of the death of Drosophila melanogaster embryos under combined exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field at various doses and modes of exposure. Mutagenic effect of combined exposure is antagonistic in nature. The antagonism is more pronounced when the following mode of exposure was used: exposure to non-ionizing pulsed magnetic field for 5 h followed by exposure to γ-radiation at doses of 3, 10, and 60 Gy. In case of reverse sequence of exposures, the antagonistic effect was statistically significant after exposure to γ-radiation at doses of 3 and 10 Gy, whereas at a dose of 20 Gy, a synergistic interaction was noted.

[The influence of diet therapy and regular physical trainings on monocyte chemoattractant protein-1 (MCP-1) secretion by monocytes among obese patients with coronary heart disease].

Chronic systemic inflammation is one of the leading pathogenetic pathways for the development of atherosclerosis in obese patients. In this regard, it seems promising to evaluate the effect of the diet and physical exertion on the proinflammatory activity of monocytes. The purpose of this research was to evaluate the effect of the diet and regular physical trainings on the secretion of monocyte chemotactic factor 1 (MCP-1) by monocytes in obese patients with coronary artery disease. Material and methods. 27 obese participants (body mass index >30 kg/m2) with a confirmed diagnosis of coronary heart disease were recruited. All participants were prescribed with 12 weeks of a specialized diet with a restriction of simple carbohydrates and salt, a 500-kcal daily energy deficit, and with inclusion of cruciferous (200 g per day), seasonal dark berries (70 g per day) and green tea (200 ml per day). The regular assisted physical trainings were also administered. The body composition, blood biochemical parameters and MCP-1 secretion rates in the primary culture of monocytes isolated from blood samples via the immunomagnetic separation method were assessed before and after the intervention. Results. As a result, after the 12-weeks intervention the reliable body weight loss (-4.0%), waist circumference (-4.2%), visceral fat (-5.4%), total cholesterol (-9.8%), LDL-cholesterol (-16.6%) and triglycerides (-26.0%), an improvement in the results of the 6-minute walk test (+10.33%) was achieved, as well as an LPS-stimulated monocytes secretion of MCP-1 decreased by 2.8 times (p=0.005). Conclusion. Overall, the results suggest that diet and regular physical activity in patients with obesity and coronary heart disease may decrease the functional "proinflammatory" activity of monocytes.

Octahedral Distortion and Displacement-Type Ferroelectricity with Switchable Photovoltaic Effect in a 3d

Because of the half-filled t_{2g}-electron configuration, the BO_{6} octahedral distortion in a 3d^{3} perovskite system is usually very limited. In this Letter, a perovskitelike oxide Hg_{0.75}Pb_{0.25}MnO_{3} (HPMO) with a 3d^{3} Mn^{4+} state was synthesized by using high pressure and high temperature methods. This compound exhibits an unusually large octahedral distortion enhanced by approximately 2 orders of magnitude compared with that observed in other 3d^{3} perovskite systems like RCr^{3+}O_{3} (R=rare earth). Essentially different from centrosymmetric HgMnO_{3} and PbMnO_{3}, the A-site doped HPMO presents a polar crystal structure with the space group Ama2 and a substantial spontaneous electric polarization (26.5 µC/cm^{2} in theory) arising from the off-center displacements of A- and B-site ions. More interestingly, a prominent net photocurrent and switchable photovoltaic effect with a sustainable photoresponse were observed in the current polycrystalline HPMO. This Letter provides an exceptional d^{3} material system which shows unusually large octahedral distortion and displacement-type ferroelectricity violating the "d^{0}-ness" rule.

[Association between remnant cholesterol levels and incident diabetic retinopathy in middle-aged and older patients with diabetes].

Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.

Mutation Effect of Ionizing and Non-Ionizing Electromagnetic Radiation on Drosophila melanogaster.

The frequency of D. melanogaster embryonic death was estimated using the method of dominant lethal mutations after exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field. γ-Radiation had a dose-dependent mutational effect on D. melanogaster. A pronounced increase in embryonic death was observed starting from a dose of 3 Gy and reaches a plateau at 60 Gy due to the maximum death of eggs. When D. melanogaster was exposed to pulsed magnetic field, the effect did not depend on the exposure time; a statistically significant genotoxic effect was detected after 5-h exposure.

[The oral microbiome in the context of systemic disease].

The oral microbiome is a community of symbiotic, commensal and opportunistic microorganisms, usually present in the form of biofilm, that plays a critical role in maintaining the homeostasis and protective function of the oral cavity. Recently, the study of the human oral microbiome to develop new diagnostic and therapeutic approaches has become a promising new area of the research in the field of personalized medicine. The aim of this review was to generalise and analyse the accumulated data on the relationship between the oral microbiome characteristics and the course of systemic diseases. Material and methods. Literature searches were performed using RSCI, PubMed, Google Scholar, and included original research data published mainly in the last 5 years. Results. The review summarized data on the role of the oral microbiome in the development of a number of systemic diseases, including alimentary diseases. The importance of the major exogenous and endogenous factors that lead to changes in the oral microbiome, including diet, macro- and micronutrient composition of foods, was highlighted. Data were provided on the main types of microorganisms associated with the development and c ourse of a number of somatic diseases, represented mainly by obligate anaerobic periodontal pathogens (Tannerella forsythia, Treponema denticola, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans). The role of the systemic inflammatory response as the main pathogenetic factor of oral dysbiosis has been described. The benefits of periodontal therapy in metabolic disorders such as diabetes mellitus, obesity, and dyslipidemia have been discussed. Promising approaches to correct oral dysbiosis have been presented. Conclusion. The knowledge of the relationships between the oral microbiome composition, the development and characteristics of the course of somatic disease can contribute to the development of new technologies for its prevention and treatment. The change in the structure of the oral microbiome observed in systemic diseases is usually accompanied by a decrease in bacterial diversity and an increase in the number of pathogenic bacteria. Lifestyle modification, dietary therapy, smoking cessation, rational use of antibacterial drugs and treatment of periodontitis play an important role in normalising the structure of the oral microbiome.

[Physical activity in sarcopenia: rehabilitation approaches in prevention and treatment of age-related muscle disorders]. / Fizicheskaya aktivnost' pri sarkopenii: reabilitatsionnye podkhody v profilaktike i lechenii vozrastnoi patologii myshechnoi tkani.

Sarcopenia is a widespread condition in the elderly people, that occurs as a result of impaired muscle structure and function and is significantly associated with reduced quality and time of life. This review represents current approaches to the diagnosis of sarcopenia with reference to recent European and Asian consensus. They include rules for the evaluation of the main muscle strength and function tests (hand dynamometry, sit-to-stand test, 6-minute walk test, physical performance battery tests, etc.), physical and instrumental methods of muscle mass analysis (densitometry, bioimpedance analysis, magnetic resonance imaging). Furthermore, the pathogenetic relationship between the lack of physical activity and muscle dysfunction in elderly people is broached, including in particular the role of myostatin, interleukin-6, somatotropin and insulin resistance. The article represents possibilities of impact of aerobic, strength and neuromuscular physical exercises on prevention and correction of sarcopenic changes in different age groups based on the analysis of current clinical studies.

The DOMON domain protein LmKnk contributes to correct chitin content, pore canal formation and lipid deposition in the cuticle of Locusta migratoria during moulting.

Insects prevent uncontrolled penetration of water and xenobiotics by producing an impermeable cuticle. The major component of the cuticle is chitin that adopts a crystalline structure thereby contributing to cuticle stability. Our understanding of the contribution of chitin to the cuticle barrier function is limited. Here, we studied the role of the DOMON domain protein Knickkopf (LmKnk) that is involved in chitin organization and cuticle permeability in the migratory locust Locusta migratoria. We show that LmKnk localizes to the chitin layer in the newly produced cuticle. Injection of double-stranded RNA targeting LmKnk (dsLmKnk) in locust nymphs caused failure of moulting to the next stage. Histological experiments revealed that apolysis, i.e., the detachment of the old cuticle from the body surface, was normal; however, the newly synthesized cuticle was thinner than the cuticle of the control insects. Indeed, chitin content dropped after suppression of LmKnk expression. As seen by transmission electron microscopy, crystalline chitin organization was lost in dsLmKnk-treated insects. In addition, the structure of pore canals, which are lipid transporting routes in the cuticle, was abnormal. Consistently, their content was reduced and, probably by consequence, lipid deposition on the cuticle was decreased after injection of dsLmKnk. Suppression of LmKnk transcript levels rendered L. migratoria more susceptible to each of four selected insecticides including malathion, chlorpyrifos, carbaryl and deltamethrin. Overall, our data show that LmKnk is needed for correct chitin amounts and organization, and their changes ultimately affect cuticular permeability in L. migratoria.

Superconductivity in a unique type of copper oxide.

The mechanism of superconductivity in cuprates remains one of the big challenges of condensed matter physics. High-T c cuprates crystallize into a layered perovskite structure featuring copper oxygen octahedral coordination. Due to the Jahn Teller effect in combination with the strong static Coulomb interaction, the octahedra in high-T c cuprates are elongated along the c axis, leading to a 3dx 2-y 2 orbital at the top of the band structure wherein the doped holes reside. This scenario gives rise to 2D characteristics in high-T c cuprates that favor d-wave pairing symmetry. Here, we report superconductivity in a cuprate Ba2CuO4-y , wherein the local octahedron is in a very exceptional compressed version. The Ba2CuO4-y compound was synthesized at high pressure at high temperatures and shows bulk superconductivity with critical temperature (T c ) above 70 K at ambient conditions. This superconducting transition temperature is more than 30 K higher than the T c for the isostructural counterparts based on classical La2CuO4 X-ray absorption measurements indicate the heavily doped nature of the Ba2CuO4-y superconductor. In compressed octahedron, the 3d3z 2-r 2 orbital will be lifted above the 3dx 2-y 2 orbital, leading to significant 3D nature in addition to the conventional 3dx 2-y 2 orbital. This work sheds important light on advancing our comprehensive understanding of the superconducting mechanism of high T c in cuprate materials.

[Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro].

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHODS: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULTS: Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 µg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 µg/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 µmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 µmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro. CONCLUSION: Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.

[Neuroendoscopy-assisted microneurosurgery for cerebellopontine angle cholesteatoma].

A total of 49 patients with cerebellopontine angle cholesteatoma from the Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University between January 2013 and January 2021 were recruited. All patients were evaluated by MRI scan before surgery and tumor resection was performed under microscope via retrosigmoid sinus approach. Then residual tumor was searched with 0°and 30°neuroendoscopy, and tumor resection was performed.Residual tumors were foundand resectedin 38 cases under theneuroendoscopy after routine microsurgery.Total and subtotalresections were performed in 44 cases and 5 cases, respectively. Complications included aseptic meningitis (n=8), cerebrospinal fluid leakage (n=1) and intracranial hematoma (n=2). Follow-up[42±3(6-72)months] was available in all patients. During follow-up, 45 cases (91.8%) had a Kar-nofsky Performance Status (KPS)score ≥80.Neuroendoscopy-assisted microsurgery for cerebellopontine angle cholesteatomas helps enhance the total resection rate and decrease the operative risk.

[Associations between gene polymorphisms of signal transducer and activator of transcription 3 and the susceptibility to hepatitis B virus related liver cirrhosis].

To investigate the associations between gene polymorphisms of signal transducer and activator of transcription 3 (STAT3) and liver cirrhosis (LC) after hepatitis B virus (HBV) infection. A case-control study was conducted in 243 patients with hepatitis B cirrhosis (HBV-LC, case group) and 486 HBV-infected subjects without LC (non-LC, control group) collected from January 2018 to September 2020 at the Changsha Central Hospital Affiliated to Nanhua University. Three single nucleotide polymorphisms (SNPs) of STAT3 gene, including rs4796793C>G, rs2293152C>G, and rs1053004T>C were selected through literature and biological information database, and the genotypes were detected by real-time fluorescent quantitative PCR (RFQ-PCR). The distribution differences of STAT3 SNPs genotypes between the two groups were compared using Chi-square test and haplotype analysis was conducted by Shesis online. The proportion of HBV C genotype in HBV-LC patients was significantly higher than that in the control group (80.91% vs. 70.79%, χ2=7.109, P=0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 vs. 1.95±0.54, t=3.801, P=0.000). The genotypes distributions of rs4796793, rs2293152, and rs1053004 were not significantly different between HBV-LC and non-LC in overall analysis and stratified analysis by gender (χ²=2.610, 1.505, 0.586, 2.653, 2.685, 1.583, 0.351, 5.388, 0.339, respectively, P>0.05 for each). Among the subjects infected with HBV genotype C, rs1053004 CC (vs. TT) significantly increased the risk of HBV-LC [odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, rs4796793 GG genotype (vs. CC) and G allele (vs. C) significantly increased the risks of HBV-LC (OR = 2.17, 95%CI: 1.11-4.23; OR = 1.45, 95%CI: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of rs4796793, rs2293152, and rs1053004 was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% vs. 35.6%, χ²=9.949, P = 0.001). The correlation between STAT3 and HBV-LC is different in HBV-infected subjects with different infection status. The HBV-infected subjects carrying haplotype rs4796793C-rs2293152G-rs1053004T of STAT3 gene have significantly decreased risk of LC.

[Chronic sacral neuromodulation for pelvic floor dysfunction in children with spina bifida]. / Lechenie narusheniya funktsii tazovykh organov u detei s mielodisplaziei metodom khronicheskoi sakral'noi neirostimulyatsii.

OBJECTIVE: To estimate the effectiveness of chronic sacral neurostimulation for neurogenic lower urinary tract dysfunction in children with spina bifida. MATERIAL AND METHODS: Eight patients with spina bifida and neurogenic lower urinary tract dysfunction underwent surgical treatment. Three patients had detrusor-sphincter dyssynergia and urinary incontinence. Five patients had detrusor overactivity and urine retention. Conservative treatment was failed in all cases. We implanted quadripolar test electrode on the S3 root through Tuohy needle under fluoroscopic control. Test stimulation was ineffective in three children with detrusor overactivity. Five patients with positive response to stimulation underwent implantation of chronic neurostimulation system. We estimated the efficacy of neurostimulation considering symptoms of neurogenic lower urinary tract dysfunction, urinary diary, PAD test and complex urodynamic examination data. RESULTS: Positive clinical effects were observed in 3 patients with detrusor-sphincter dyssynergia and 2 patients with detrusor overactivity. Clinical effect included improvement in urine leakage and higher bladder volume. In patients with urinary retention, we revealed voluntary urination and less number of daily catheterization procedures. In one patient, clinical effect of chronic stimulation regressed within 3 month after surgery. CONCLUSION: Preliminary results of chronic sacral neuromodulation confirmed its advisability in children with neurogenic lower urinary tract dysfunction. Patients with detrusor-sphincter dyssynergia had better results compared to those with detrusor overactivity.

Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and its role in osteoclastogenesis.

Anti-citrullinated protein/peptide antibodies (ACPA) play important roles in the pathogenesis of rheumatoid arthritis (RA). ACPA-positive (ACPA+ ) and ACPA-negative (ACPA- ) RA were suggested to be different disease subsets, with distinct differences in genetic variation and clinical outcomes. The aims of the present study were to compare gene expression profiles in ACPA+ and ACPA- RA, and to identify novel candidate gene signatures that might serve as therapeutic targets. Comprehensive transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from ACPA+ and ACPA- RA patients and healthy controls was performed via RNA sequencing. A validation cohort was used to further investigate differentially expressed genes via polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Spearman's correlation test was used to evaluate the correlation of differentially expressed genes and the clinical and laboratory data of the patients. The role of differentially expressed genes in osteoclastogenesis was further investigated. Expression of C-X-C motif chemokine ligand 2 (CXCL2) was significantly increased in ACPA+ RA than in ACPA- RA, which was validated in PBMCs and serum. CXCL2 promoted the migration of CD14+ monocytes and increased osteoclastogenesis in RA patients. RAW264.7 macrophages were used to investigate specific mechanisms, and the results suggested that CXCL2 stimulated osteoclastogenesis via extracellular receptor kinase (ERK) mitogen-activated protein kinase (MAPK) and nuclear factor kappa B pathways. In conclusion, CXCL2 was highly expressed in ACPA+ RA than in ACPA- RA. CXCL2 promoted osteoclastogenesis and was related to bone erosion in RA, which suggests that the blockade of CXCL2 might be a novel strategy for the treatment of RA.

Directional massless Dirac fermions in a layered van der Waals material with one-dimensional long-range order.

One or a few layers of van der Waals (vdW) materials are promising for applications in nanoscale electronics. Established properties include high mobility in graphene, a large direct gap in monolayer MoS2, the quantum spin Hall effect in monolayer WTe2 and so on. These exciting properties arise from electron quantum confinement in the two-dimensional limit. Here, we use angle-resolved photoemission spectroscopy to reveal directional massless Dirac fermions due to one-dimensional confinement of carriers in the layered vdW material NbSi0.45Te2. The one-dimensional directional massless Dirac fermions are protected by non-symmorphic symmetry, and emerge from a stripe-like structural modulation with long-range translational symmetry only along the stripe direction as we show using scanning tunnelling microscopy. Our work not only provides a playground for investigating further the properties of directional massless Dirac fermions, but also introduces a unique component with one-dimensional long-range order for engineering nano-electronic devices based on heterostructures of vdW materials.

Dual Orbital Degeneracy Lifting in a Strongly Correlated Electron System.

The local structure of NaTiSi_{2}O_{6} is examined across its Ti-dimerization orbital-assisted Peierls transition at 210 K. An atomic pair distribution function approach evidences local symmetry breaking preexisting far above the transition. The analysis unravels that, on warming, the dimers evolve into a short range orbital degeneracy lifted (ODL) state of dual orbital character, persisting up to at least 490 K. The ODL state is correlated over the length scale spanning ∼6 sites of the Ti zigzag chains. Results imply that the ODL phenomenology extends to strongly correlated electron systems.

Physics-informed machine learning: case studies for weather and climate modelling.

Machine learning (ML) provides novel and powerful ways of accurately and efficiently recognizing complex patterns, emulating nonlinear dynamics, and predicting the spatio-temporal evolution of weather and climate processes. Off-the-shelf ML models, however, do not necessarily obey the fundamental governing laws of physical systems, nor do they generalize well to scenarios on which they have not been trained. We survey systematic approaches to incorporating physics and domain knowledge into ML models and distill these approaches into broad categories. Through 10 case studies, we show how these approaches have been used successfully for emulating, downscaling, and forecasting weather and climate processes. The accomplishments of these studies include greater physical consistency, reduced training time, improved data efficiency, and better generalization. Finally, we synthesize the lessons learned and identify scientific, diagnostic, computational, and resource challenges for developing truly robust and reliable physics-informed ML models for weather and climate processes. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

[In vivo study of liposome-modified polyetheretherketone implant on bacteriostasis and osseointegration].

OBJECTIVE: To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates. METHODS: Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis. RESULTS: The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo. CONCLUSION: Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.

[Differential diagnosis of pure ground glass nodules in lung with spectral CT imaging].

Objective: To evaluate the differential diagnostic performance of quantitative parameters derived from the spectral CT imagingin pure ground-glass nodules. Methods: A total of 44 patients with pure ground glass nodules underwent chest energy spectrum CT and with known subsequently pathological findings in the Imaging Department of the Second Affiliated Hospital of Soochow University from August 2017 to September 2019 were retrospectively analyzed. Among them, there are 18 males and 26 females, aged from 26 to 79 (51±12) years. They were divided into as the inflammatory group (n=12), pre-invasive adenocarcinoma group (n=17) and invasive adenocarcinoma group (n=15). The aforementioned three groups were further reclassified as non-invasive adenocarcinoma group (inflammatory lesion+pre-invasive lesion) and invasive adenocarcinoma group in order to evaluating the values of water concentration (WC) for the determination of adenocarcinoma infiltration status. The values of WC derived from the arterial and venous phase of the lesion, iodine concentration (IC), standardized iodine concentration (NIC) were measured respectively.The slope of the energy spectral curve (K40-70KeV) derived from the arterial and venous phase of the lesion was also calculated. One-way ANOVA analysis was performed to compare the differences of the three groups and the multiple comparison method was used for further comparing. Intraclass correlation efficient (ICC) was used to assess the consistency of the three times of measurements. The area under curve(AUC) of Receiver Operating Characteristic (ROC) was conducted to evaluate the diagnostic performance of water based values. Results: The values of WC in the arterial and venous phases were significantly different. As in the inflammatory group, the pre-invasive lesion group and the invasive adenocarcinoma group, the values of WC was (291.95±58.66) mg/cm3, (297.61±63.96) mg/cm3and (374.52±60.62) mg/cm3 of the arterial phase, and (277.07±33.78) mg/cm3, (291.74±50.49) mg/cm3 and (373.33±75.12) mg/cm3 of the venous phase, respectively(all P<0.05). Further comparison demonstrated that no significant difference was observed for the values of WC derived from the arterial phases and venous phases between the inflammatory lesion group and the pre-invasive lesion group (all P>0.05).There were an significant differences between the invasive adenocarcinoma group, the inflammatory lesion group and the pre-invasive lesion group (all P<0.05). The values of WC derived from the venous phase achieved the largest AUC (0.770) for differentiating invasive adenocarcinoma from non-invasive adenocarcinoma (inflammatory lesions+pre-invasive lesions) in the pure ground glass nodules. The sensitivity and specificity were 66.67% and 93.10%, respectively, when using 349.31 mg/cm³ as the optimal threshold. The slope of the spectral curve and iodine-related parameters (IC, NIC) derived from arterial or venous phases among the three groups were not significantly different (all P>0.05). Conclusion: The values of WC derived from the spectral CT can better distinguish inflammatory, pre-invasive lesions and invasive adenocarcinoma, which is helpful for the qualitative analysis for pure ground glass nodules.