Cavitation-on-a-Chip Enabled Size-Specific Liposomal Drugs for Selective Pharmacokinetics and Pharmacodynamics.

The size of liposomal drugs has been demonstrated to strongly correlate with their pharmacokinetics and pharmacodynamics. While the microfluidic method successfully achieves the production of liposomes with well-controlled sizes across various buffer/lipid flow rate ratio (FRR) settings, any adjustments to the FRR inevitably influence the concentration, encapsulation efficiency (EE), and stability of liposomal drugs. Here we describe a controllable cavitation-on-a-chip (CCC) strategy that facilitates the precise regulation of liposomal drug size at any desired FRR. The CCC-enabled size-specific liposomes exhibited striking differences in uptake and biodistribution behaviors, thereby demonstrating distinct antitumor efficacy in both tumor-bearing animal and melanoma patient-derived organoid (PDO) models. Intriguingly, as the liposome size decreased to approximately 80 nm, the preferential accumulation of liposomal drugs in the liver transitioned to a predominant enrichment in the kidneys. These findings underscore the considerable potential of our CCC approach in influencing the pharmacokinetics and pharmacodynamics of liposomal nanomedicines.

Air pollution's numerical, spatial, and temporal heterogeneous impacts on childhood hand, foot and mouth disease: a multi-model county-level study from China.

BACKGROUND: While stationary links between childhood hand, foot and mouth disease (HFMD) and air pollution are known, a comprehensive study on their heterogeneous relationships (nonstationarity), jointly considering numerical, temporal and spatial dimensions, has not been reported. METHODS: Monthly HFMD incidence and air pollution data were collected at the county level from Sichuan-Chongqing, China (2009-2011), alongside meteorological and social environmental covariates. Key influential factors were identified using random forest (RF) under the stationary assumption. Factors' numerically, temporally, and spatially heterogeneous relationships with HFMD were assessed using generalized additive model (GAM) and geographically and temporally weighted regression (GTWR). RESULTS: Our findings highlighted the relatively higher stationary contributions of fine particulate matter (PM2.5) and ozone (O3) to HFMD incidence across Sichuan-Chongqing counties. We further uncovered heterogeneous impacts of PM2.5 and O3 from three nonstationary perspectives. Numerically, PM2.5 showed an inverse 'V'-shaped relationship with HFMD incidence, while O3 exhibited a complex pattern, with increased HFMD incidence at low PM2.5 and moderate O3 concentrations. Temporally, PM2.5's impact peaked in autumn and was weakest in spring, whereas O3's effect was strongest in summer. Spatially, hotspot mapping revealed high-risk clusters for PM2.5 impact across all seasons, with notable geographical variations, and for O3 in spring, summer, and autumn, concentrated in specific regions of Sichuan-Chongqing. CONCLUSIONS: This study underscores the nuanced and three-perspective heterogeneous influences of air pollution on HFMD in small areas, emphasizing the need for differentiated, localized, and time-sensitive prevention and control strategies to enhance the precision of dynamic early warnings and predictive models for HFMD and other infectious diseases, particularly in the fields of environmental and spatial epidemiology.

Analysis of sterilizer allocation and related factors in dental health-care settings in Yunnan Province, China: a cross-sectional study.

OBJECTIVE: To investigate the status and related factors of sterilizers in dental health-care settings in Yunnan Province, with the aim of providing a theoretical basis for the health administrative department to formulate regional quality control programs and systems, proposing reasonable suggestions for optimizing the allocation of sterilizer resources in Yunnan's dental health-care settings, thereby improving resource utilization efficiency. METHODS: This cross-sectional survey was conducted in 2600 dental health-care settings in Yunnan Province in March 2020. Uni-variable linear regression, multi-variable linear regression, curve fitting and threshold effect analysis were used to understand the relationship between dental units and sterilizers. RESULTS: A total of 2600 dental health-care settings were included. The disinfection and sterilization work were mainly completed by the dental department in 1510(58.1%) institutions. 44(1.7%) institutions were not allocated sterilization equipment, and 1632 (62.8%) had only one sterilizer. The median allocation of sterilizers was 1.0. Uni-variable linear regression showed significant differences in covariates such as dental unit, dental handpiece, disinfection equipment, dentist, and dental assistant, which were more sensitive (p < 0.001) and statistically significant. The adjusted model was more stable in the multi-variable linear regression, and the differences in covariates between different settings were statistically significant. Curve fitting revealed an S-shaped curvilinear relationship between the number of dental units and sterilizers in oral healthcare settings. CONCLUSION: The disinfection and sterilization work was mainly completed by the dental department in dental health-care settings in Yunnan Province. Sterilizer allocation increases with the number of dental units, but some institutions have insufficient allocation of sterilizer and manpower resources, resulting in certain risks of infection control. Thus, it is necessary to strengthen supervision, inspection and regional quality control work in infection control of dentistry.

A High-Efficiency Bioorthogonal Tumor-Membrane Reactor for In Situ Selective and Sustained Prodrug Activation.

The site-specific activation of bioorthogonal prodrugs has provided great opportunities for reducing the severe side effects of chemotherapy. However, the precise control of activation location, sustained drug production at the target site, and high bioorthogonal reaction efficiency in vivo remain great challenges. Here, we propose the construction of tumor cell membrane reactors in vivo to solve the above problems. Specifically, tumor-targeted liposomes with efficient membrane fusion capabilities are generated to install the bioorthogonal trigger, the amphiphilic tetrazine derivative, on the surface of tumor cells. These predecorated tumor cells act as many living reactors, transforming the tumor into a "drug factory" that in situ activates an externally delivered bioorthogonal prodrug, for example intratumorally injected transcyclooctene-caged doxorubicin. In contrast to the rapid elimination of cargo that is encapsulated and delivered by liposomes, these reactors permit stable retention of bioorthogonal triggers in tumor for 96 h after a single dose of liposomes via intravenous injection, allowing sustained generation of doxorubicin. Interestingly, an additional supplement of liposomes will compensate for the trigger consumed by the reaction and significantly improve the efficiency of the local reaction. This strategy provides a solution to the efficacy versus safety dilemma of tumor chemotherapy.

One-Step Formation of Targeted Liposomes in a Versatile Microfluidic Mixing Device.

Targeted liposomes, as a promising carrier, have received tremendous attention in COVID-19 vaccines, molecular imaging, and cancer treatment, due to their enhanced cellular uptake and payload accumulation at target sites. However, the conventional methods for preparing targeted liposomes still suffer from limitations, including complex operation, time-consuming, and poor reproducibility. Herein, a facile and scalable strategy is developed for one-step construction of targeted liposomes using a versatile microfluidic mixing device (MMD). The engineered MMD provides an advanced synthesis platform for multifunctional liposome with high production rate and controllability. To validate the method, a programmed death-ligand 1 (PD-L1)-targeting aptamer modified indocyanine green (ICG)-liposome (Apt-ICG@Lip) is successfully constructed via the MMD. ICG and the PD-L1-targeting aptamer are used as model drug and targeting moiety, respectively. The Apt-ICG@Lip has high encapsulation efficiency (89.9 ± 1.4%) and small mean diameter (129.16 ± 5.48 nm). In vivo studies (PD-L1-expressing tumor models) show that Apt-ICG@Lip can realize PD-L1 targeted photoacoustic imaging, fluorescence imaging, and photothermal therapy. To verify the versatility of this approach, various targeted liposomes with different functions are further prepared and investigated. These experimental results demonstrate that this method is concise, efficient, and scalable to prepare multifunctional targeted liposomal nanoplatforms for molecular imaging and disease theranostics.

Conjugated Polymer-Based Nanocomposites for Pressure Sensors.

Flexible sensors are the essential foundations of pressure sensing, microcomputer sensing systems, and wearable devices. The flexible tactile sensor can sense stimuli by converting external forces into electrical signals. The electrical signals are transmitted to a computer processing system for analysis, realizing real-time health monitoring and human motion detection. According to the working mechanism, tactile sensors are mainly divided into four types-piezoresistive, capacitive, piezoelectric, and triboelectric tactile sensors. Conventional silicon-based tactile sensors are often inadequate for flexible electronics due to their limited mechanical flexibility. In comparison, polymeric nanocomposites are flexible and stretchable, which makes them excellent candidates for flexible and wearable tactile sensors. Among the promising polymers, conjugated polymers (CPs), due to their unique chemical structures and electronic properties that contribute to their high electrical and mechanical conductivity, show great potential for flexible sensors and wearable devices. In this paper, we first introduce the parameters of pressure sensors. Then, we describe the operating principles of resistive, capacitive, piezoelectric, and triboelectric sensors, and review the pressure sensors based on conjugated polymer nanocomposites that were reported in recent years. After that, we introduce the performance characteristics of flexible sensors, regarding their applications in healthcare, human motion monitoring, electronic skin, wearable devices, and artificial intelligence. In addition, we summarize and compare the performances of conjugated polymer nanocomposite-based pressure sensors that were reported in recent years. Finally, we summarize the challenges and future directions of conjugated polymer nanocomposite-based sensors.

The Synergistic Effects between Sulfobetaine and Hydrophobically Modified Polyacrylamide on Properties Related to Enhanced Oil Recovery.

In order to explore the mechanism responsible for the interactions in the surfactant-polymer composite flooding and broaden the application range of the binary system in heterogeneous oil reservoirs, in this paper, the influences of different surfactants on the viscosity of two polymers with similar molecular weights, partially hydrolyzed polyacrylamide (HPAM) and hydrophobically modified polyacrylamide (HMPAM), were studied at different reservoir environments. In addition, the relationship between the surfactant-polymer synergistic effects and oil displacement efficiency was also investigated. The experimental results show that for HPAM, surfactants mainly act as an electrolyte to reduce its viscosity. For HMPAM, SDBS and TX-100 will form aggregates with the hydrophobic blocks of polymer molecules, reducing the bulk viscosity. However, zwitterionic surfactant aralkyl substituted alkyl sulfobetaine BSB molecules can build "bridges" between different polymer molecules through hydrogen bonding and electrostatic interaction. After forming aggregates with HMPAM molecules, the viscosity will increase. The presence of two polymers all weakened the surfactant oil-water interfacial membrane strength to a certain extent, but had little effect on the interfacial tension. The synergistic effect of the "bridge" between HMPAM and BSB under macroscopic conditions also occurs in the microscopic pores of the core, which has a beneficial effect on improving oil recovery.

Salivary microbiome and metabolome analysis of severe early childhood caries.

BACKGROUND: Severe early childhood caries (SECC) is an inflammatory disease with complex pathology. Although changes in the oral microbiota and metabolic profile of patients with SECC have been identified, the salivary metabolites and the relationship between oral bacteria and biochemical metabolism remains unclear. We aimed to analyse alterations in the salivary microbiome and metabolome of children with SECC as well as their correlations. Accordingly, we aimed to explore potential salivary biomarkers in order to gain further insight into the pathophysiology of dental caries. METHODS: We collected 120 saliva samples from 30 children with SECC and 30 children without caries. The microbial community was identified through 16S ribosomal RNA (rRNA) gene high-throughput sequencing. Additionally, we conducted non-targeted metabolomic analysis through ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry to determine the relative metabolite levels and their correlation with the clinical caries status. RESULTS: There was a significant between-group difference in 8 phyla and 32 genera in the microbiome. Further, metabolomic and enrichment analyses revealed significantly altered 32 salivary metabolites in children with dental caries, which involved pathways such as amino acid metabolism, pyrimidine metabolism, purine metabolism, ATP-binding cassette transporters, and cyclic adenosine monophosphate signalling pathway. Moreover, four in vivo differential metabolites (2-benzylmalate, epinephrine, 2-formaminobenzoylacetate, and 3-Indoleacrylic acid) might be jointly applied as biomarkers (area under the curve = 0.734). Furthermore, the caries status was correlated with microorganisms and metabolites. Additionally, Spearman's correlation analysis of differential microorganisms and metabolites revealed that Veillonella, Staphylococcus, Neisseria, and Porphyromonas were closely associated with differential metabolites. CONCLUSION: This study identified different microbial communities and metabolic profiles in saliva, which may be closely related to caries status. Our findings could inform future strategies for personalized caries prevention, detection, and treatment.

Bioinspired Gradient Stretchable Aerogels for Ultrabroad-Range-Response Pressure-Sensitive Wearable Electronics and High-Efficient Separators.

Broad-range-response pressure-sensitive wearable electronics are urgently needed but their preparation remains a challenge. Herein, we report unprecedented bioinspired wearable electronics based on stretchable and superelastic reduced graphene oxide/polyurethane nanocomposite aerogels with gradient porous structures by a sol-gel/hot pressing/freeze casting/ambient pressure drying strategy. The gradient structure with a hot-pressed layer promotes strain transfer and resistance variation under high pressures, leading to an ultrabroad detection range of 1 Pa-12.6 MPa, one of the broadest ranges ever reported. They can withstand 10 000 compression cycles under 1 MPa, which can't be achieved by traditional flexible pressure sensors. They can be applied for broad-range-response electronic skins and monitoring various physical signals/motions and ultrahigh pressures of automobile tires. Moreover, the gradient aerogels can be used as high-efficient gradient separators for water purification.

Pore-forming activity and structural autoinhibition of the gasdermin family.

Inflammatory caspases cleave the gasdermin D (GSDMD) protein to trigger pyroptosis, a lytic form of cell death that is crucial for immune defences and diseases. GSDMD contains a functionally important gasdermin-N domain that is shared in the gasdermin family. The functional mechanism of action of gasdermin proteins is unknown. Here we show that the gasdermin-N domains of the gasdermin proteins GSDMD, GSDMA3 and GSDMA can bind membrane lipids, phosphoinositides and cardiolipin, and exhibit membrane-disrupting cytotoxicity in mammalian cells and artificially transformed bacteria. Gasdermin-N moved to the plasma membrane during pyroptosis. Purified gasdermin-N efficiently lysed phosphoinositide/cardiolipin-containing liposomes and formed pores on membranes made of artificial or natural phospholipid mixtures. Most gasdermin pores had an inner diameter of 10­14 nm and contained 16 symmetric protomers. The crystal structure of GSDMA3 showed an autoinhibited two-domain architecture that is conserved in the gasdermin family. Structure-guided mutagenesis demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis. These findings reveal the mechanism for pyroptosis and provide insights into the roles of the gasdermin family in necrosis, immunity and diseases.

Dual-Template Magnetic Molecularly Imprinted Polymer for Simultaneous Determination of Spot Urine Metanephrines and 3-Methoxytyramine for the Diagnosis of Pheochromocytomas and Paragangliomas.

A novel dual-template magnetic molecularly imprinted polymer (MMIP) was synthesized to extract normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT) from spot urine samples. As the adsorbent of dispersive solid-phase extraction (d-SPE), the MMIP was prepared using dopamine and MN as dual templates, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the crosslinking reagent and magnetic nanoparticles as the magnetic core. NMN, MN, 3-MT and creatinine (Cr) in spot urine samples were selectively enriched by d-SPE and detected by HPLC-fluorescence detection/ultraviolet detection. The peak area (A) ratios of NMN, MN and 3-MT to Cr were used for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). The results showed that the adsorption efficiencies of MMIP for target analytes were all higher than 89.0%, and the coefficient variation precisions of intra-assay and inter-assay for the analytes were within 4.9% and 6.3%, respectively. The recoveries of the analytes were from 93.2% to 112.8%. The MMIP was still functional within 14 days and could be reused at least seven times. The d-SPE and recommended solid-phase extraction (SPE) were both used to pretreat spot urine samples from 18 PPGLs patients and 22 healthy controls. The correlation coefficients of ANMN/ACr and AMN/ACr between d-SPE and SPE were both higher than 0.95. In addition, the areas under the receiver operator curves for spot urine ANMN/ACr, AMN/ACr and plasma free NMN and MN were 0.975, 0.773 and 0.990, 0.821, respectively, indicating the two methods had the similar performances. The d-SPE method took only 20 min, which was effective in clinical application.

Application of Duplex Droplet Digital PCR Detection of miR-888 and miR-891a in Semen Identification.

OBJECTIVES: To establish a system for simultaneous detection of miR-888 and miR-891a by droplet digital PCR (ddPCR), and to evaluate its application value in semen identification. METHODS: The hydrolysis probes with different fluorescence modified reporter groups were designed to realize the detection of miR-888 and miR-891a by duplex ddPCR. A total of 75 samples of 5 body fluids (including peripheral blood, menstrual blood, semen, saliva and vaginal secretion) were detected. The difference analysis was conducted by Mann-Whitney U test. The semen differentiation ability of miR-888 and miR-891a was evaluated by ROC curve analysis and the optimal cut-off value was obtained. RESULTS: There was no significant difference between the dual-plex assay and the single assay in this system. The detection sensitivity was up to 0.1 ng total RNA, and the intra- and inter-batch coefficients of variation were less than 15%. The expression levels of miR-888 and miR-891a detected by duplex ddPCR in semen were both higher than those in other body fluids. ROC curve analysis showed that the AUC of miR-888 was 0.976, the optimal cut-off value was 2.250 copies/µL, and the discrimination accuracy was 97.33%; the AUC of miR-891a was 1.000, the optimal cut-off value was 1.100 copies/µL, and the discrimination accuracy was 100%. CONCLUSIONS: In this study, a method for detection of miR-888 and miR-891a by duplex ddPCR was successfully established. The system has good stability and repeatability and can be used for semen identification. Both miR-888 and miR-891a have high ability to identify semen, and the discrimination accuracy of miR-891a is higher.

Highly sensitive and selective fluorescent monomer/polymer probes for Hg2+ and Ag+ recognition and imaging of Hg2+ in living cells.

The detection of heavy metals such as Hg2+ and Ag+ is important and urgent. In this work, - NO2/- NH2/C=S boron dipyrromethene small molecular derivatives were synthesized at first. Then they were incorporated into polymer chains. The macromolecular fluorescent probes were obtained via Sonogashira reaction using the small molecular probes as building blocks. The as-prepared small-molecule fluorescent probe BO3 exhibits high sensing performance for Hg2+. By introducing it into macromolecules, the sensing ability still remains, and even more, the recognition performance is improved. The macromolecular fluorescent probes P1, P2, and P3 also have high recognition ability for Ag+ with a binding ratio of 2:1 (metal ion to probe ratio). Through the study of the sensing mechanism and the recycling experiments, it is found that the probes responded by the photo-induced electron transfer mechanism and can be recycled and reused. At the same time, BO3, P2, and P3 show excellent recognition performance for Hg2+ in living cells and zebrafish. Living cell imaging experiments indicated that these fluorescent probes had good cell membrane permeability and low cytotoxicity, and could realize bioimaging of Hg2+. Therefore, the application value of these fluorescent probes could be enlarged. Graphical abstract.

Highly Sensitive Ratiometric Self-Assembled Micellar Nanoprobe for Nitroxyl and Its Application In Vivo.

Nitroxyl (HNO) is a derivative of nitric oxide (NO) that plays an essential role in various biological and pharmacological events. Until now, the in situ trapping and specific detection of HNO in living samples is still challenging. In this project, we fabricated a novel BODIPY-based micellar nanoprobe for monitoring nitroxyl in vitro and in vivo in ratiometric mode in aqueous solution. The probe (P-BODIPY-N) contains an asymmetrical BODIPY dye for fluorescent signaling and a diphenylphosphinobenzoyl as the trigger moiety; then we encapsulated P-BODIPY-N into the hydrophobic interior of an amphiphilic copolymer (mPEG-DSPE) and prepared a novel BODIPY-based micellar nanoprobe: NP-BODIPY-N. As far as we know, this probe is the first reported ratiometric fluorescent nanoprobe for HNO, which exhibits ultrasensitivity, high selectivity, and good biocompatibility. Above all, this nanoprobe shows favorable cellular uptaken and was successfully used to detect intracellular HNO released by Angeli's salt in living cells and zebrafish larvae. These results indicate that our newly designed nanoprobe will provide a promising tool for the studies of HNO in living system.

One-Pot Synthesis of a Bismuth Selenide Hexagon Nanodish Complex for Multimodal Imaging-Guided Combined Antitumor Phototherapy.

For integrating therapy and diagnosis into a single nanoparticle for higher antitumor efficiency and lower toxicity, our group designed a smart theranostic nanoplatform based on a hyaluronic acid-doped polypyrrole-coated bismuth selenide loading with a zinc phthalocyanine nanodish complex (Bi2Se3@HA-doped PPy/ZnPc) for multimodal imaging-guided combined phototherapy. Moreover, we expect that the HA-doped PPy smart shell for the surface functionalization will also be applied to a variety of 2D nanomaterials sharing a similar structure with Bi2Se3 to broaden their applications in biomedicine. The Bi2Se3 hexagon nanodish was synthesized via a simple and safe solution-based method compared to the commonly adopted ones. A one-pot synthesis of the naoncomplex was carried out by adding HA during the polypyrrole coating on the Bi2Se3 process, and then it was further loaded with ZnPc. Besides the good ability for infrared thermal, photoacoustic, fluorescence, and X-ray computed tomography imaging, the nanodish complex has its own high photoheat conversion efficiency for photothermal therapy, and it has remarkable optical absorption of the coefficient for photodynamic therapy. With the EPR effect of nanoparticles and the CD44-targeted effect of HA, the tumor-growth inhibition ratio of Bi2Se3@HA-doped PPy/ZnPc for PTT/PDT was as high as 96.4%, compared with that of the PTT (68.0%) or PDT (24.3%) alone, showing an excellent combined therapeutic effect. Moreover, no obvious toxicity in vivo was caused by the nanoparticles. Thus, such a Bi2Se3@HA-doped PPy/ZnPc nanodish complex has promise for real-time monitoring and precise, high-efficiency antitumor treatment.

Is it Beneficial to Reuse the Balloon in Percutaneous Kyphoplasty for the Treatment of Non-Neoplastic Vertebral Compression Fractures?

BACKGROUND Percutaneous kyphoplasty (PKP) has been widely used to treat vertebral compression fractures (VCFs). Bilateral percutaneous punctures are always performed to access the fractured vertebrae. However, the procedure has expensive clinical costs, especially the cost for the device, which creates a heavy financial burden for patients. MATERIAL AND METHODS Data from 49 patients who have single-level non-neoplastic vertebral compression fracture (VCF) were collected for 12 months after treated by PKP, including 21 cases that used bilateral puncture with single balloon (S group) and 28 cases that used bilateral puncture with double balloon (D group). We assessed the clinical (visual analogue scale, VAS) and radiological (vertebral height and kyphotic angle, KA) outcomes. Cost data (gross medical cost, cost for the device and cost for drugs) were obtained from the medical bill of each patient. RESULTS Baseline patient variables were similar between the two groups except the compensation (S group

"Smart" molecularly imprinted monoliths for the selective capture and easy release of proteins.

A new thermally switchable molecularly imprinted monolith for the selective capture and release of proteins has been designed. First, a generic poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith reacted with ethylenediamine followed by functionalization with 2-bromoisobutyryl bromide to introduce the initiator for atom transfer radical polymerization. Subsequently, a protein-imprinted poly(N-isopropylacrylamide) layer was grafted onto the surface of the monolithic matrix by atom transfer radical polymerization. Scanning electron microscopy and energy-dispersive X-ray spectroscopy of the cross-sections of imprinted monoliths confirmed the formation of dense poly(N-isopropylacrylamide) brushes on the pore surface. The imprinted monolith exhibited high specificity and selectivity toward its template protein myoglobin over competing proteins and a remarkably large maximum adsorption capacity of 1641 mg/g. Moreover, this "smart" imprinted monolith featured thermally responsive characteristics that enabled selective capture and easy release of proteins triggered only by change in temperature with water as the mobile phase and avoided use of stronger organic solvents or change in ionic strength and pH.

Cementless bilateral synchronous total hip arthroplasty in ankylosing spondylitis with hip ankylosis.

PURPOSE: This study was a retrospective analysis of early and mid-term clinical effects and perioperative management of cementless bilateral synchronous total hip arthroplasty (THA) in patients with ankylosing spondylitis (AS) with bilateral hip ankylosis. METHODS: Fifteen AS patients (30 hips) with bilateral hip ankylosis were managed with cementless bilateral synchronous THA. Surgical outcome was evaluated using the visual analogue scale (VAS), the range of motion and the Harris score. RESULTS: The mean follow-up period was 29.3 months. At the last follow-up visit, the VAS score decreased from 7.53 ± 0.99 before the operation to 2.40 ± 0.91. The Harris score increased from 24.8 ± 7.42 before the operation to 83.8 ± 4.61. The total range of motion increased from 78.73 ± 14.53 before the operation to 209.73 ± 16.19 after the operation. After the operation, there was one case of early hip dislocation, one case of femoral nerve stretch injury and one case of superficial incision infection. There were no cases of deep venous thrombosis. X-ray examinations did not show prosthetic loosening or displacement. CONCLUSION: AS patients with bilateral hip ankylosis can be treated with cementless bilateral synchronous THA, which could greatly improve hip joint function without significant complications. The clinical effects proved to be satisfactory.

Management of oblique root fracture in the middle third of two maxillary immature central incisors with severe caries in mixed dentitions: a case report.

Mid-root fractures are rare injuries in young permanent teeth and tend to have poor prognoses. This study presents a case of oblique root fracture of both maxillary immature central incisors in the middle third accompanied by delayed dental visit and severe caries of all primary teeth. After restoring all the primary and permanent teeth that needed stabilization, the coronal fragments were repositioned and stabilized with a flexible splint consisting of orthodontic wire and composite resin. A comprehensive and sequential dental treatment for other oral diseases and oral hygiene instructions were provided. A 16-month follow-up revealed that the two injured young permanent incisors were healed, surrounded by hard tissues and continued to grow both in length of the root and thickness of the root canal wall, with significant improvement in oral hygiene. Based on the outcome of this case, initial stabilization without endodontic therapy could be considered a successful treatment modality for young permanent teeth with oblique root fracture due to the growth of fractured teeth with vital pulp and the maintenance of natural dentition.

Xanthine oxidase immobilized cellulose membrane-based colorimetric biosensor for screening and detecting the bioactivity of xanthine oxidase inhibitors.

Xanthine oxidase (XO) is a typical target for hyperuricemia and gout, for which there are only three commercial xanthine oxidase inhibitors (XOIs): febuxostat, topiroxostat and allopurinol. However, these inhibitors have problems such as low bioactivity and several side effects. Therefore, the development of novel XOIs with high bioactivity for the treatment of hyperuricemia and gout is urgently needed. In this work we constructed a XO immobilized cellulose membrane colorimetric biosensor (XNCM) by the TEMPO oxidation, amide bond coupling and nitro blue tetrazolium chloride (NBT) loading method. As expected, the XNCM was able to detect xanthine, with high selectivity and sensitivity by colorimetric method with a distinctive color change from yellow to purple, which can be easily observed by the naked-eye in just 8 min without any complex instrumentation. In addition, the XNCM sensor performed screening of 21 different compounds and have been successfully pre-screened out XOIs with biological activity. Most importantly, the XNCM was able to quantitatively detect the IC50 values of two commercial inhibitors (febuxostat and allopurinol). All the results confirmed that the XNCM is a simple and effective tool which can be used for the accelerated screening of XOIs and has the potential to uncover additional XOIs.