Semiconducting Polymer Nanoparticles-Manganese Based Chemiluminescent Platform for Determining Total Antioxidant Capacity in Diabetic Mice.

The total antioxidant capacity (TAC) is a key indicator of the body's resistance to oxidative stress injury in diabetic patients. The measurement of TAC is important for effectively evaluating the redox state to prevent and control the occurrence of diabetes complications. However, there is a lack of a simple, convenient, and reliable method to detect the total antioxidant capacity in diabetes. Herein, we design a novel chemiluminescent platform based on semiconducting polymer nanoparticles-manganese (SPNs-MnVII) to detect the total antioxidant capacity of urine in diabetic mice. We synthesize semiconducting polymer nanoparticles with four different structures and discover the ability of MnVII to produce singlet oxygen (1O2) that is employed to excite thiophene-based SPNs (PFODBT) to emit near-infrared chemiluminescence. Notably, the chemiluminescent intensity has a good linear relationship with the concentration of MnVII (detection limit: 2.8 µM). Because antioxidants (e.g., glutathione or ascorbic acid) can react with MnVII, such a chemiluminescent tool of SPNs (PFODBT)-MnVII can detect the glutathione or ascorbic acid with a larger responsive range. Furthermore, the total antioxidant capacity of urine from mice is evaluated via SPNs (PFODBT)-MnVII, and there are statistically significant differences between diabetic and healthy mice. Thus, this new chemiluminescent platform of SPNs (PFODBT)-MnVII is convenient, efficient, and sensitive, which is promising for monitoring antioxidant therapy of diabetes.

A possible strategy for generating polymer chains with an entanglement-free structure.

We propose a possible strategy that may experimentally generate long polymeric chains with an entanglement-free structure. The basic idea is designing the conditions to restrict polymer chains from growing along the surface with an obviously concave curvature. This strategy is proved to effectively reduce the chance of forming both inter- and intra-molecular entanglements, which is quite similar to the self-avoiding random walking of chains on a two dimensional plane. We believe that this kind of chain growth strategy may supply a kind of possible explanation on the formation of the entanglement-free structure of chromosomes, which also have tremendously large molecular weight. Besides, this study also guides experimentalists on synthesizing specific entanglement-free functional polymeric or biological materials.

Characterization of microbiota in acute leukemia patients following successful remission induction chemotherapy without antimicrobial prophylaxis.

PURPOSE: In the present study, we characterized the microbiomes of acute leukemia (AL) patients who achieved complete remission following remission induction chemotherapy (RIC) as outpatients, but who did not receive antimicrobials to treat or prevent febrile neutropenia. METHODS: Saliva and stool samples from 9 patients with acute myeloid leukemia, 11 patients with acute lymphoblastic leukemia, and 5 healthy controls were subjected to 16S ribosomal RNA sequencing at baseline and at 3 months following RIC. Only patients who achieved remission at 3 months post-treatment were included. We excluded anyone who used antimicrobials within 2 months of enrollment or at any time during the study period. RESULTS: At baseline, the relative abundances of species of Prevotella maculosa (P=0.001), Megasphaera micronuciformis (P=0.014), Roseburia inulinivorans (P=0.021), and Bacteroides uniformis (P=0.004) in saliva and Prevotella copri (P=0.002) in the stools of controls were significantly higher than in AL patients. Following RIC, the relative abundances of Eubacterium sp. oral clone DO008 (P=0.012), Leptotrichia sp. oral clone IK040 (P=0.002), Oribacterium sp. oral taxon 108 (P=0.029), Megasphaera micronuciformis (P=0.016), TM7 phylum sp. oral clone DR034 (P<0.001), Roseburia inulinivorans (P=0.034), Actinomyces odontolyticus (P=0.014), Leptotrichia buccalis (P=0.005), and Prevotella melaninogenica (P=0.046) in saliva and Lactobacillus fermentum (P=0.046), Coprococcus catus (P=0.050), butyrate-producing bacterium SS3/4 (P=0.013), and Bacteroides coprocola (P=0.027) in the stools of AL patients were significantly greater than in controls. CONCLUSION: Following RIC, several taxa are changed in stool and salvia samples of AL patients. Our results warrant future large-scale multicenter studies to examine whether the microbiota might have an effect on clinical outcomes of AL patients.

[The Ultrasonographic Features of Female Reproductive System Extraosseous Ewing's Sarcoma].

OBJECTIVE: This study investigated the clinicopathological traits and ultrasound features of female reproductive system extraosseous Ewing's sarcoma (EES) and explored the diagnostic value of ultrasonography for this condition. METHODS: Cases of female pelvic EES diagnosed and treated at our hospital between June 2009 and June 2019 were included in this study. Pathology data and ultrasound manifestations were assessed retrospectively to summarize the clinical traits and ultrasound features of female reproductive system EES. Based on the results, recommendations for the ultrasonography-based diagnosis of this disease were proposed. RESULTS: During the 10-year study period, 13 female patients were diagnosed with EES in the pelvic cavity based on the results of postoperative pathology tests. The age of the patients ranged from 8 mouth to 40 years, and no patients demonstrated specific clinical symptoms. However, an examination of tumor biomarkers revealed that certain patients had elevated levels of CA125. In the 13 patients, 19 lesions were identified, including 16 that involved the reproductive system. The primary ultrasound manifestation was uneven, low-echo solidity or cystic solidity, exhibiting large size, irregular shape, and unclear boundary. A few patients had concurrent ascites. Although some lesions lacked blood supply, the blood supply of most lesions was medium to abundant, and the blood flow was mostly characterized by low resistant. Almost none of the lesions were definitively diagnosed preoperatively. CONCLUSIONS: Preoperative definitive diagnosis of EES in the female reproductive system remains a great clinical challenge. Although certain clinical traits and ultrasound features are associated with this disease, and color Doppler ultrasonography might provide vital information indicating the presence of EES, the final diagnosis still depends on the pathological test results of the patients.

Antibiofouling Zwitterionic Gradational Membranes with Moisture Retention Capability and Sustained Antimicrobial Property for Chronic Wound Infection and Skin Regeneration.

Nonadherent wound dressings with moisture management and long-lasting antibacterial properties have great significance for wound healing clinically. Herein, a novel multicomponent zwitterionic gradational membrane is fabricated by a co-electrospinning method to realize low biofouling and favorable moisture control as well as long-acting antibacterial properties during the chronic wound-healing process. The obtained membrane possesses excellent anti-biofouling performance that effectively resists protein, bacteria, and cell adhesion according to in vitro antifouling evaluation. Furthermore, the gradational co-electrospinning method grants the composite membrane with moisture retention capability which could effectively absorb wound exudate and maintain a moisture healing environment. Additionally, in vivo and in vitro antibacterial investigations reflect that the composite membrane has excellent long-acting antibacterial property. Moreover, in vivo wound healing assessment confirms that the prepared membrane significantly reduces the complete wound healing time than commercial wound dressing. These results highlight such a zwitterionic gradational membrane as an advanced wound dressing to meet the various requirements for chronic wound infection and skin tissue regeneration in clinical applications.

Meta-analysis of the clinical value of oxymatrine on sustained virological response in chronic hepatitis B.

UNLABELLED:  Introduction. Oxymatrine (OMTR) is widely used for the treatment of chronic hepatitis B (CHB) in China. Several recent reports revealed that OMTR together with interferon yielded a higher sustained virological response (SVR) than interferon alone. AIM: To elucidate this topic using meta-analysis of data from published randomized controlled trials (RCTs). MATERIAL AND METHODS: The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database and China Biomedical Database were searched to identify RCTs that evaluated SVR to interferón therapies and interferon plus OMTR therapies in CHB patients. RESULTS: The literature search yielded 238 studies, and 11 RCTs comprising 968 patients matched the selection criteria. Overall, SVR was significantly higher in patients treated with interferon plus OMTR than in patients treated with interferon alone (SVR: 60.7 vs. 39.8%; relative risk: 1.56; 95% confidence interval: 1.37-1.77; p < 0.05). Combined therapy of interferon plus OMTR were also superior to interferon therapies alone in achieving the endof-treatment viral response, alaninetransaminase normalization, HBeAg loss, and HBeAg seroconversion. CONCLUSIONS: Combined therapy of interferon plus OMTR may yield a higher SVR than interferon therapies. The exact outcome needs to perform rigorously designed, multicenter, and large randomized controlled trials.

Molecular progress in research on fruit astringency.

Astringency is one of the most important components of fruit oral sensory quality. Astringency mainly comes from tannins and other polyphenolic compounds and causes the drying, roughening and puckering of the mouth epithelia attributed to the interaction between tannins and salivary proteins. There is growing interest in the study of fruit astringency because of the healthy properties of astringent substances found in fruit, including antibacterial, antiviral, anti-inflammatory, antioxidant, anticarcinogenic, antiallergenic, hepatoprotective, vasodilating and antithrombotic activities. This review will focus mainly on the relationship between tannin structure and the astringency sensation as well as the biosynthetic pathways of astringent substances in fruit and their regulatory mechanisms.

Notch Signaling Hydrogels Enable Rapid Vascularization and Promote Dental Pulp Tissue Regeneration.

Successful dental pulp regeneration is closely associated with rapid revascularization and angiogenesis, processes driven by the Jagged1(JAG1)/Notch signaling pathway. However, soluble Notch ligands have proven ineffective in activating this pathway. To overcome this limitation, a Notch signaling hydrogel is developed by indirectly immobilizing JAG1, aimed at precisely directing the regeneration of vascularized pulp tissue. This hydrogel displays favorable mechanical properties and biocompatibility. Cultivating dental pulp stem cells (DPSCs) and endothelial cells (ECs) on this hydrogel significantly upregulate Notch target genes and key proangiogenic markers expression. Three-dimensional (3D) culture assays demonstrate Notch signaling hydrogels improve effectiveness by facilitating encapsulated cell differentiation, enhancing their paracrine functions, and promoting capillary lumen formation. Furthermore, it effectively communicates with the Wnt signaling pathway, creating an odontoinductive microenvironment for pulp-dentin complex formation. In vivo studies show that short-term transplantation of the Notch signaling hydrogel accelerates angiogenesis, stabilizes capillary-like structures, and improves cell survival. Long-term transplantation further confirms its capability to promote the formation of pulp-like tissues rich in blood vessels and peripheral nerve-like structures. In conclusion, this study introduces a feasible and effective hydrogel tailored to specifically regulate the JAG1/Notch signaling pathway, showing potential in advancing regenerative strategies for dental pulp tissue.

Development of a multifunctional food packaging for meat products by incorporating carboxylated cellulose nanocrystal and beetroot extract into sodium alginate films.

Consumers' pursuit for safe meat products is challenging to develop smart food packaging with proper mechanical properties and multifunctional properties. Therefore, this work attempted to introduce carboxylated cellulose nanocrystal (C-CNC) and beetroot extract (BTE) into sodium alginate (SA) matrix films to enhance their mechanical properties and endow them with antioxidant properties and pH-responsive capacity. The rheological results showed the C-CNC and BTE were consistently dispersed in the SA matrix. The incorporation of C-CNC made the surface and cross-section of the films rough but still dense, thus significantly improving the mechanical properties of the films. The integration of BTE provided antioxidant properties and pH responsiveness without significantly changing the thermal stability of the film. The highest tensile strength (55.74 ± 4.52 MPa) and strongest antioxidant capacities were achieved for the SA-based film with BTE and 10 wt% C-CNC. Additionally, the films possessed higher UV-light barrier properties after incorporating BTE and C-CNC. More notably, the pH-responsive films discolored when TVB-N value exceeded 18.0 mg/100 g during storage of pork at 4 °C and 20 °C, respectively. Therefore, the SA-based film with enhanced mechanical and functional properties has a high potential for quality detection in smart food packaging applications.

[Comparison of activated carbon and ultrafiltration technique in the production process of huoxue tongluo injection].

OBJECTIVE: To research the applicability of activated carbon and ultrafiltration technique in the production process of Huoxue Tongluo Injection. METHODS: The kinetic-turbidimetric method was used to determine the content of bacterial endotoxins in Huoxue Tongluo solution. Particle size change in Huoxue Tongluo solution was determined by nanometer particle size instrument before and after the use of different concentration activated carbon and different molecular weight ultrafiltration membrane. RESULTS: The removal efficacy of bacterial endotoxins was 65.2%, 77.5%, 80.4% by using three concentrations of active carbon at 0.05%, 0.10%, 0.30% in Huoxue Tongluo Injection, respectively. It was above 95% by using cutoff molecular weight both 5 kDa and 10 kDa ultrafiltration membrane. Measure results by nanometer particle size instrument showed that particle size of filter liquor by 10 kDa cutoff molecular weight ultrafiltration membrane was much smaller than that of by use of different concentration activated carbon. CONCLUSION: Ultrafiltration method is more suitable to the removal of bacterial endotoxins. The solution is more clear after using ultrafiltration method, and large particles of solution is removed. The ultrafiltration method provides the basis for injection production.

Insight into the uptake, accumulation, and metabolism of the fungicide phenamacril in lettuce (Lactuca sativa L.) and radish (Raphanus sativus L.).

The fungal species Fusarium can cause devastating disease in agricultural crops. Phenamacril is an extremely specific cyanoacrylate fungicide and a strobilurine analog that has excellent efficacy against Fusarium. To date, information on the mechanisms involved in the uptake, accumulation, and metabolism of phenamacril in plants is scarce. In this study, lettuce and radish were chosen as model plants for a comparative analysis of the absorption, accumulation, and metabolic characteristics of phenamacril from a polluted environment. We determined the total amount of phenamacril in the plant-water system by measuring the concentrations in the solution and plant tissues at frequent intervals over the exposure period. Phenamacril was readily taken up by the plant roots with average root concentration factor ranges of 60.8-172.7 and 16.4-26.9 mL/g for lettuce and radish, respectively. However, it showed limited root-to-shoot translocation. The lettuce roots had a 2.8-12.4-fold higher phenamacril content than the shoots; whereas the radish plants demonstrated the opposite, with the shoots having 1.5 to 10.0 times more phenamacril than the roots. By the end of the exposure period, the mass losses from the plant-water systems reached 72.0% and 66.3% for phenamacril in lettuce and radish, respectively, suggesting evidence of phenamacril biotransformation. Further analysis confirmed that phenamacril was metabolized via hydroxylation, hydrolysis of esters, demethylation, and desaturation reactions, and formed multiple transformation products. This study furthers our understanding of the fate of phenamacril when it passes from the environment to plants and provides an important reference for its scientific use and risk assessment.

[Effect on elimination of pyrogen and effectual components of Panax notoginseng saponins by ultrafiltration membranes of different cut-off molecular weight and different materials].

OBJECTIVE: To study the elimination effect of bacterial endotoxins and the transmittance of Panax notoginseng saponins by ultrafiltration membranes of different cut-off molecular weight and different materials. METHODS: The kinetic-turbidimetric method was used to determine the content of bacterial endotoxins in Panax notoginseng saponins solution before and after using the ultrafiltration. The change of the contents of active components was examined by HPLC,using notoginsennoside R1, ginsennoside Rg1, ginsennoside Rb1 and ginsennoside Rd as the mark components. RESULTS: The removal rate of bacterial endotoxin fell along with the increasing of membrane aperture. The removal rate was 20. 69% by ultrafiltration membranes of 100 KDa with polysulfone material,less than those of other ultrafiltration membranes with polysulfone material. But the removal rate of bacterial endotoxin by E membranes of blend materials was higher than those of other ultrafiltration membranes with polysulfone material. The contents of active components filtered by E membranes of blend materials was more than that of ultrafiltration membranes of 100 KDa with polysulfone material. CONCLUSION: The applicability of ultrafiltration membranes of large cut-off molecular weight and blend materials of effectual component in Panax notoginseng saponins and elimination of pyrogen is good.

3D-printed Poly-Lactic Co-Glycolic Acid (PLGA) scaffolds in non-critical bone defects impede bone regeneration in rabbit tibia bone.

BACKGROUND: An increasing number of bone graft materials are commercially available and vary in their composition, mechanism of action, costs, and indications. OBJECTIVE: A commercially available PLGA scaffold produced using 3D printing technology has been used to promote the preservation of the alveolar socket after tooth extraction. We examined its influence on bone regeneration in long bones of New Zealand White rabbits. METHODS: 5.0-mm-diameter circular defects were created on the tibia bones of eight rabbits. Two groups were studied: (1) control group, in which the bone defects were left empty; (2) scaffold group, in which the PLGA scaffolds were implanted into the bone defect. Radiography was performed every two weeks postoperatively. After sacrifice, bone specimens were isolated and examined by micro-computed tomography and histology. RESULTS: Scaffolds were not degraded by eight weeks after surgery. Micro-computed tomography and histology showed that in the region of bone defects that was occupied by scaffolds, bone regeneration was compromised and the total bone volume/total volume ratio (BV/TV) was significantly lower. CONCLUSION: The implantation of this scaffold impedes bone regeneration in a non-critical bone defect. Implantation of bone scaffolds, if unnecessary, lead to a slower rate of fracture healing.

Tannic acid/Mg2+-based versatile coating to manipulate the osteoimmunomodulation of implants.

Instead of directly stimulating osteogenesis, endowing an implant surface with a favourable osteoimmunomodulatory (OIM) function has emerged as a new effective strategy to enhance osteointegration. Though metal-phenolic coatings have demonstrated to possess an immunomodulatory function, their potential application in manipulating an osteoimmune response has not been well explored. Herein, in order to develop a simple, rapid and universal coating method to impart excellent OIM to hard tissue implants, tannic acid (TA) and Mg2+ were selected to form a coating on Ti plate based on metal-phenolic chemistry. Besides its virtues of simplicity, ultrafastness, low-cost, and versatility, another merit for the coating method is that it can easily combine the unique functions of metal ions and phenolic ligands. The chelated Mg2+ can not only activate macrophage polarization towards the anti-inflammatory phenotype but also directly stimulate the osteogenic differentiation of bone marrow-derived stem cells (BMSCs). TA motifs rendered the coating with an excellent reactive oxygen species (ROS) scavenging capacity. TA and Mg2+ showed synergistic effects on regulating macrophage biological behaviour, suppressing its polarization towards the M1 phenotype, and promoting its polarization towards the M2 phenotype. In vivo histological analysis also demonstrated that the TA/Mg2+ coating could effectively inhibit the host response. Finally, the formed osteoimmune environment obviously enhanced the osteogenic differentiation of BMSCs. The above results demonstrated that the designed TA/Mg2+ coating not only possessed the function of directly stimulating osteogenesis but also the function of manipulating OIM to a desired one. Hence, it has great potential to be applied on advanced hard tissue implants to enhance osteointegration.

A novel coating with universal adhesion and inflammation-responsive drug release functions to manipulate the osteoimmunomodulation of implants.

The immune response elicited by the bone endoprosthesis is currently considered an important factor that affects its interfacial osteointegration. In this work, a metal-phenolic-based drug-loaded coating with universal adhesion properties and intelligent drug delivery feature was created to promote osteointegration by manipulating a beneficial osteoimmune microenvironment. A novel pro-drug with inflammation-responsive release function was firstly synthesized via the esterification reaction between tannic acid (TA) and indometacin (IND), and then the coating was developed by chelating it with Fe3+. In the normal biological environment, the coating was stable, while, in the inflammatory environment, the release of TA and IND motifs could be triggered by the overexpressed esterase. The released TA and IND displayed synergistic effects on macrophage polarization, leading to a downregulation expression of pro-inflammatory cytokines, and an upregulation expression of anti-inflammatory cytokines and osteogenic-related factors. When stimulated by a conditioned medium generated by macrophages seeded onto the coating, the osteogenic differentiation potential of BMSCs was significantly enhanced. Finally, the designed coating significantly promoted the osteointegration of the implant, demonstrated by the increase of the bone-implant contact by two times. Additionally, the coating was substrate-independent and can be formed within seconds without special equipment, thus, it showed great potential applications to endow advanced hard tissue implants with favorable osteoimmunomodulation.

A tumor microenvironment-induced absorption red-shifted polymer nanoparticle for simultaneously activated photoacoustic imaging and photothermal therapy.

Tumor microenvironment-responsive therapy has enormous application potential in the diagnosis and treatment of cancer. The glutathione (GSH) level has been shown to be significantly increased in tumor tissues. Thus, GSH can be used as an effective endogenous molecule for diagnosis and tumor microenvironment-activated therapy. In this study, we prepared a tumor microenvironment-induced, absorption spectrum red-shifted, iron-copper co-doped polyaniline nanoparticle (Fe-Cu@PANI). The Cu(II) in this nanoparticle can undergo a redox reaction with GSH in tumors. The redox reaction induces a red shift in the absorption spectrum of the Fe-Cu@PANI nanoparticles from the visible to the near-infrared region accompanying with the etching of this nanoparticle, which simultaneously activates tumor photoacoustic imaging and photothermal therapy, thereby improving the accuracy of in vivo tumor imaging and the efficiency of photothermal therapy. The nanoparticle prepared in this study has broad application prospects in the diagnosis and treatment of cancer.

An investigation of the pharmacological applications used for the Ancient Egyptian systemic model 'ra-ib' compared with modern Traditional Chinese Medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Ancient Egyptian texts only offer glimpses into their conceptual understandings of the inner-body and illness manifestation. Explanations of how prescribed materia medica were believed to work are rare and obscure, often resulting in modern approximations for ancient terminology such as 'ra-ib'-an ancient Egyptian classification predominantly translated as 'stomach'-leading to misunderstandings of historical texts, and therefore their use of pharmacology. AIM OF THE STUDY: To investigate the ra-ib and the explanatory models of illness from the Egyptian perspective, and to explore the link between these and the prescribed selection of materia medica. To then compare the conceptual mechanics of these treatment strategies with those of another non-Western tradition-namely Traditional Chinese Medicine (TCM)-to provide further insight into potential conceptual frameworks. MATERIALS AND METHODS: We conducted a case study of a unit of Ancient Egyptian texts focusing on the ra-ib. Totalling 34 prescriptions, the first stage lexicographically analysed the texts using cognitive linguistic and translation theories to produce our new understanding. This enabled our comparison of the mechanics of materia medica usage within these texts with those found in TCM outlined by the Pharmacopoeia of the Peoples Republic of Pharmacopeia of the People's Republic of China 2015 for the relevant ingredients. RESULTS: the study demonstrated that-rather than denoting the organ 'stomach'-ra-ib instead constitutes a system running from the mouth, downward to the anus. This is best translated as 'inner thoroughfare', and changes the way in which we attempt to understand potential motivations in the selection of ingredients. By exploring common themes in the use of eleven securely translated ingredients from the Egyptian corpus and the Pharmacopoeia of the People's Republic of China-representing a modern traditional system which understands the body via a series of interconnected systems-we were able to highlight certain themes which might be 'universal' to system-based traditions; this provided new insights into the Egyptian motivations for treatment selection. CONCLUSIONS: Having gained the ancient view of the body and illness, cultural comparisons are important for providing further potential insights and clarifications of a discontinued historical healing tradition. The new understanding of the ra-ib from our study greatly changes the way in which we understand the dynamics of Egyptian ethnopharmacological source material from this period.

Genetic Variation of Multiple Serotypes of Enteroviruses Associated with Hand, Foot and Mouth Disease in Southern China.

Enteroviruses (EVs) species A are a major public health issue in the Asia-Pacific region and cause frequent epidemics of hand, foot and mouth disease (HFMD) in China. Mild infections are common in children; however, HFMD can also cause severe illness that affects the central nervous system. To molecularly characterize EVs, a prospective HFMD virological surveillance program was performed in China between 2013 and 2016. Throat swabs, rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals. EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions (RT-PCRs). Then, the complete VP1 regions of enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16) and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny. Of the 2836 enrolled HFMD patients, 2,517 (89%) were EV positive. The most frequently detected EVs were CVA16 (32.5%, 819), CVA6 (31.2%, 785), and EV-A71 (20.4%, 514). The subgenogroups CVA16_B1b, CVA6_D3a and EV-A71_C4a were predominant in China and recombination was not observed in the VP1 region. Sequence analysis revealed amino acid variations at the 30, 29 and 44 positions in the VP1 region of EV-A71, CVA16 and CVA6 (compared to the respective prototype strains BrCr, G10 and Gdula), respectively. Furthermore, in 21 of 24 (87.5%) identified EV-A71 samples, a known amino acid substitution (D31N) that may enhance neurovirulence was detected. Our study provides insights about the genetic characteristics of common HFMD-associated EVs. However, the emergence and virulence of the described mutations require further investigation.

The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study.

BACKGROUND: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. METHODS: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. FINDINGS: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. INTERPRETATION: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. FUNDING: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

Infectious intracranial aneurysm: endovascular treatment with onyx case report and review of the literature.

Intracranial infectious (mycotic) aneurysms are very rare, but continue to be challenging and technically demanding, which need careful diagnosis and therapy. We present an 18-year-old man with an intracranial infectious aneurysm located on the left posterior cerebral artery who was successfully treated with endovascular embolization by a liquid embolic agent (onyx) and who recovered well.