A supramolecular fluorescence sensor array for the differentiation of multiple anions and prediction of iodine in artificial urine using machine learning.

The simultaneous discrimination and detection of multiple anions in an aqueous solution has been a major challenge due to their structural similarity and low charge radii. In this study, we have constructed a supramolecular fluorescence sensor array based on three host-guest complexes to distinguish five anions (F-, Cl-, Br-, I-, and ClO-) in an aqueous solution using anionic-induced fluorescence quenching combined with linear discriminant analysis. Due to the different affinities of the three host-guest complexes for each anion the anion quenching efficiency for each host-guest complex was likewise different, and the five anions were well recognized. The fluorescence sensor array not only distinguished anions at different concentrations (0.5, 10, and 50 µM) with 100% accuracy but also showed good linearity within a certain concentration range. The limit of detection (LOD) was < 0.5 µM. Our interference study showed that the developed sensor array had good anti-interference ability. The practicability of the developed sensor array was also verified by the identification and differentiation of toothpaste brands with different fluoride content and the prediction of the iodine concentration in urine combined with machine learning.

Comparative effectiveness of PEEK rods versus titanium alloy rods in cervical fusion in a new sheep model.

BACKGROUND: Pedicle screw and rod instrumentation based on titanium can produce satisfying strength and stiffness for spinal fusion. However, excessive stiffness produced by titanium rods may cause stress shielding. Thus, polyetheretherketone (PEEK) rods with a low modulus of elasticity were introduced as substitutes for titanium rods. The purpose of this paper is to compare the effectiveness of PEEK rods versus titanium alloy rods in anterior spinal fusion with a new sheep model. METHODS: Sheep models of anterior-posterior cervical fusion were innovatively adopted in our study. Twenty-four sheep were randomly divided into a control group and a treatment group that received anterior-posterior cervical fixation with titanium rods or PEEK rods, respectively. Then, surgical segments were harvested and assessed by X-ray, micro-CT and histological examination to evaluate the efficiency of bone fusion. RESULTS: No complications related to fixation were found during the research process. The results of the X-ray showed a stronger spinal fusion in the PEEK rod groups than in the titanium rod group at 12 weeks postoperatively, and both groups underwent bone fusion at 24 weeks postoperatively. The results of micro-CT showed that fixation with PEEK rods achieved better bone ingrowth at an early postoperative stage (12 weeks) compared to fixation with titanium rods (bone volume fraction (BVF): 20.26 ± 4.36% vs 14.48 ± 3.49%, p < 0.05). The same trend was detected in the histological analysis, where the mineralized bone fraction in the experiment group (21.01 ± 3.48%) was significantly higher than that in the control group (16.73 ± 2.95%). In addition, better osseointegration was found in the experiment group at the early postoperative stage at 12 weeks (bone apposition (BA): 16.22 ± 3.24% vs 11.67 ± 3.63%, p < 0.05). However, there were no significant differences at 24 weeks postoperatively. CONCLUSION: PEEK rods can be used safely in a sheep model of anterior-posterior cervical fixation. Compared to traditional titanium rods, earlier and more evident bone fusion was found in the PEEK rods group. These slides can be retrieved under Electronic Supplementary Material.

Acute and subchronic toxicity of Ag+-laden liposomes on Daphnia magna: the effect of encapsulation.

The toxic effects of various substances on Daphnia magna (D. magna) observed through traditional waterborne uptake may involve alterations to the nutritional quality of the contaminated algae and culture media. It is essential to find an alternative delivery method that will not affect the nutritional quality of D. magna's diet in order to elucidate the mechanisms of dietary metal toxicity. Therefore, this study examined the application of liposome encapsulation on the dietary toxicity of D. magna. Ag+-laden liposomes were prepared and the Ag encapsulation efficiency and inhibition effect on algae growth were examined. Then, acute and 14-day subchronic studies were performed to examine the effect of Ag+-laden liposomes on D. magna. The EC50 for the 24 h immobilization test was 10.59 µg/L for Ag+-laden liposomes and 3.07 µg/L for Ag+. In terms of subchronic effects, the estimated ECx values under the Ag+-laden liposome condition were always higher than the direct exposure condition. Furthermore, the bioaccumulation of Ag+-laden liposomes was about 1.68 times lower than direct exposure. Generally, Ag+-laden liposomes produced less efficient toxicity than direct exposure, e.g., lower D. magna mortality, production of more neonates, higher intrinsic rate of natural increase (rm), earlier time to first brood, and higher enzyme activities.

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice.

BACKGROUND/AIMS: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. METHODS: Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. RESULTS: The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. CONCLUSIONS: The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.

Expression, purification, crystallization and preliminary X-ray diffraction analysis of swine leukocyte antigen 2 complexed with a CTL epitope AS64 derived from Asia1 serotype of foot-and-mouth disease virus.

BACKGROUND: Currently, the structural characteristics of the swine major histocompatibility complex (MHC) class I molecule, also named swine leukocyte antigen class I (SLA-I) molecule need to be further clarified. RESULTS: A complex of SLA-I constituted by an SLA-2*HB01 molecule with swine ß2-microglobulin and a cytotoxic T lymphocyte (CTL) epitope FMDV-AS64 (ALLRSATYY) derived from VP1 protein (residues 64-72) of Asia 1 serotype of foot-and-mouth disease virus (FMDV) was expressed, refolded, purified and crystallized. By preliminary X-ray diffraction analysis, it was shown that the diffraction resolution of the crystal was 2.4 Å and the space group belonged to P212121 with unit cell parameters a = 48.37, b = 97.75, c = 166.163 Å. CONCLUSION: This research will be in favor of illuminating the structural characteristics of an SLA-2 molecule associated with a CTL epitope derived from Asia1 serotype of FMDV.

Rhizobacterial Strain Bacillus megaterium BOFC15 Induces Cellular Polyamine Changes that Improve Plant Growth and Drought Resistance.

Plant-growth-promoting rhizobacteria can improve plant growth, development, and stress adaptation. However, the underlying mechanisms are still largely unclear. We investigated the effects of Bacillus megaterium BOFC15 on Arabidopsis plants. BOFC15 produced and secreted spermidine (Spd), a type of polyamine (PA) that plays an important role in plant growth. Moreover, BOFC15 induced changes in the cellular PAs of plants that promoted an increase of free Spd and spermine levels. However, these effects were remarkably abolished by the addition of dicyclohexylamine (DCHA), a Spd biosynthetic inhibitor. Additionally, the inoculation with BOFC15 remarkably increased plant biomass, improved root system architecture, and augmented photosynthetic capacity. Inoculated plants also displayed stronger ability to tolerate drought stress than non-inoculated (control) plants. Abscisic acid (ABA) content was notably higher in the inoculated plants than in the control plants under drought stress and polyethylene glycol (PEG)-induced stress conditions. However, the BOFC15-induced ABA synthesis was markedly inhibited by DCHA. Thus, microbial Spd participated in the modulation of the ABA levels. The Spd-producing BOFC15 improved plant drought tolerance, which was associated with altered cellular ABA levels and activated adaptive responses.

Outbreak of febrile illness caused by coxsackievirus A4 in a nursery school in Beijing, China.

BACKGROUND: Coxsackievirus A4 (CV-A4) is classified as human enterovirus A according to its serotype. CV-A4, an etiological agent of hand, foot, and mouth disease, affects children worldwide and can circulate in closed environments such as schools and hospitals for long periods. FINDINGS: An outbreak of febrile illness at a nursery school in Beijing, China, was confirmed to be caused by CV-A4. Phylogenetic analysis of the complete genome of the isolated strain showed that the virus belongs to the same cluster as the predominant CV-A4 strain in China. This outbreak was controlled by effective measures. CONCLUSIONS: The early identification of the pathogen and timely intervention may be the most critical factors in controlling an outbreak caused by CV-A4 in a preschool.

The molecule of DC-SIGN captures enterovirus 71 and confers dendritic cell-mediated viral trans-infection.

BACKGROUND: Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease that occurs in young children. Neither antiviral agents nor vaccines are available for efficiently combating viral infection. Study of EV71-host interplay is important for understanding viral infection and developing strategies for prevention and therapy. Here the interactions of EV71 with human dendritic cells were analyzed. METHODS: EV71 capture, endocytosis, infection, and degradation in monocyte-derived dendritic cells (MDDCs) were detected by Flow cytometry or real-time (RT-) PCR, and MDDCs-mediated EV71 trans-infection of RD cells was determined via coculture system. Cell morphology or viability was monitored with microscopy or flow cytometry. SiRNA interference was used to knock down gene expression. RESULTS: MDDCs can bind EV71, but these loaded-EV71 particles in MDDCs underwent a rapid degradation in the absence of efficient replication; once the captured EV71 encountered susceptible cells, MDDCs efficiently transferred surface-bound viruses to target cells. The molecule of DC-SIGN (DC-specific intercellular adhesion molecule-3 grabbing nonintegrin) mediated viral binding and transfer, because interference of DC-SIGN expression with specific siRNAs reduced EV71 binding and impaired MDDC-mediated viral trans-infection, and exogenous expression of DC-SIGN molecule on Raji cell initiated viral binding and subsequent transmission. CONCLUSION: MDDCs could bind efficiently EV71 viruses through viral binding to DC-SIGN molecule, and these captured-viruses could be transferred to susceptible cells for robust infection. The novel finding of DC-mediated EV71 dissemination might facilitate elucidation of EV71 primary infection and benefit searching for new clues for preventing viruses from initial infection.

Biomimetic design of platelet-rich plasma controlled release bacterial cellulose/hydroxyapatite composite hydrogel for bone tissue engineering.

Bacterial cellulose (BC) hydrogel is renowned in the field of tissue engineering for its high biocompatibility, excellent mechanical strength, and eco-friendliness. Herein, we present a biomimetic mineralization method for preparing BC/hydroxyapatite (HAP) composite hydrogel scaffolds with different mineralization time and ion concentration of the mineralized solution. Spherical HAP reinforcement enhanced bone mineralization, thereby imparting increased bioactivity to BC matrix materials. Subsequently, platelet-rich plasma (PRP) was introduced into the scaffold. The PRP-loaded hydrogel enhanced the release of growth factors, which promoted cell adhesion, growth, and bone healing. After 3 weeks of MC3T3-E1 cell-induced osteogenesis, PRP positively affected cell differentiation in BC/HAP@PRP scaffolds. Overall, these scaffolds exhibited excellent biocompatibility, mineralized nodule formation, and controlled release in vitro, demonstrating great potential for application in bone tissue repair.

Intramyocardial delivery of HMGB1 by a novel thermosensitive hydrogel attenuates cardiac remodeling and improves cardiac function after myocardial infarction.

BACKGROUND: High-mobility group box 1 (HMGB1), a nuclear protein, has been recently reported to attenuate cardiac remodeling after myocardial infarction (MI). This study was designed to investigate whether this effect could be strengthened by local intramyocardial injection of HMGB1 along with a novel Dex-PCL-HEMA/PNIPAAm hydrogel and ascertain its possible mechanism of action. METHODS: Rat models were induced by coronary artery ligation. Phosphate-buffered solution, Dex-PCL-HEMA/PNIPAAm hydrogel, HMGB1 in phosphate-buffered solution, or HMGB1 in hydrogel was injected into a peri-infarcted area of cardiac tissue immediately after MI. RESULTS: The injection of HMGB1 along with hydrogel improved cardiac function and reduced collagen content. Additionally, the number of c-Kit/Ki67, α-sarcomeric/MEF2C, and α-sarcomeric/Ki67 cells were increased significantly compared with the results of using either agent alone. CONCLUSIONS: HMGB1 injection with Dex-PCL-HEMA/PNIPAAm hydrogel attenuates cardiac remodeling and improves cardiac function after MI by inducing myocardial regeneration.

[Dynamic changes in PD-1, TLR3, and TLR4 surface expression on peripheral blood mononuclear cells in chronic hepatitis C patients undergoing peg-IFNalpha-2a plus ribavirin combination therapy].

OBJECTIVE: To investigate the dynamic changes in expression of programmed death (PD)-1, Toll-like receptor (TLR)3, and TLR4 on the surface of peripheral blood mononuclear cells (PBMCs) in patients with chronic hepatitis C (CHC) that occur in response to pegylated-interferon alpha-2a (peg-IFNalpha-2a) plus ribavirin (RBV) combination therapy, and to analyze the relation to achievement of sustained virological response (SVR). METHODS Twenty-three CHC patients and 10 healthy controls were enrolled in the study. All CHC patients underwent 48 weeks of combination therapy with peg-IFNalpha-2a (180 microg, subcutaneous injection, once weekly) plus RBV (15 microg/kg, oral, once daily). Total PBMCs were isolated from both groups (CHC patients at treatment week 0, 12, 24, and 48 and post-treatment week 24; controls at enrollment) and subjected to flow cytometric analysis of PD-1, TLR3, and TLR4 surface expression. In addition, serum levels of alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels were analyzed by enzymatic assay and the AmpliPrep/COBAS (Roche) nucleic acid amplification test, respectively. SVR was defined as undetectable levels of HCV RNA at post-treatment week 24. Intergroup differences were assessed by one-way ANOVA. RESULTS: The expression ratios of PD-1, TLR4 and PD-1: TLR4 on PBMCs were significantly higher in CHC patients before therapy than in the healthy controls (45.20 +/- 7.12% vs. 16.82 +/- 4.13%, 58.45 +/- 15.13% vs. 21.09 +/- 2.89%, and 35.54 +/- 7.69% vs. 14.12 +/- 2.89%; all P < 0.05). In contrast, the expression ratios of TLR3 and PD-1:TLR3 were slightly, but not significantly, higher in CHC patients before therapy than in the healthy controls (P > 0.05). During the course of peg-IFNalpha-2a plus RBV combination therapy, the expression ratios of PD-1 and TLR4 on PBMCs showed a decreasing trend, while TLR3 expression showed an increasing trend. Furthermore, CHB patients who achieved SVR at post-treatment week 24 had a significantly different expression ratio of PD-1 and TLR3 than those who did not achieve SVR (P < 0.05). CONCLUSION: Surface expression of PD-1, TLR4, and PD-1:TLR4 is up-regulated in the total PBMCs of CHC patients. Peg-IFNalpha-2a plus RBV treatment-induced suppression of HCV replication results in a significant reduction in PD-1 and TLR4 expression on the surface of PBMCs, but a remarkably elevated level of TLR3 expression. The dynamic change in PD-1 and TLR3 expression on PBMCs that occurs during antiviral therapy may be related to achievement of SVR.

Characterization of PDL1 enhanced siRNA/albumin liposome for effective therapeutic function in lung cancer.

PURPOSE: The applications of liposomes are limited due to poor structural stability and short drug circulation time. This study aims to build an albumin-based liposomal delivery system to provide strategies for tumor specificity, efficient gene delivery and effective release of albumin liposomes. METHODS: In this study, siRNA loaded PDL1-targeted albumin liposome was constructed for the treatment of lung cancer and its function was evaluated. Physical parameters such as particle size, potential and infrared spectrum were detected and microscopic morphology was observed by electron microscopy to detect the binding and uptake capacity of albumin liposome with cells. The optimal preparation process and binding ratio of PDL1-targeted albumin liposome/siRNA complex were determined. RESULTS: The constructed siRNA loaded PDL1-targeted albumin liposomes has low toxicity, high loading rate and tumor cell targeted gene therapy ability. Moreover, it increased T cell activation and down-regulated siRNA expression, effectively realizing the inhibition of lung cancer cells. CONCLUSION: The results showed that the PDL1-targeted albumin liposome could be used as a high efficient delivery vector of siRNA, and was a high efficient and safe nano vector for tumor targeted gene therapy.

The Significance of Odontoid Incidence in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: Observational study. OBJECTIVE: To analyze the cervical sagittal parameters for standing Digital radiography (DR) and supine Magnetic resonance imaging (MRI), and to further clarify the relationship between odontoid incidence (OI) and cervical spondylotic myelopathy (CSM). METHODS: 52 CSM patients aged 54.46 ± 2.89 years underwent both standing DR and supine MRI scans of cervical spine between November 2021 and November 2022. OI, odontoid tilt (OT), C2 slope (C2S), T1 slope (T1S), C0-2 angle, C2-7 angle (cervical lordosis [CL]), and T1S-CL were measured in both DR and MRI images using Surgimap (Version 2.3.2.1). Pearson correlation and linear regression were used to compare these parameters between the two modalities. RESULTS: Cervical sagittal parameters, including OI, OT, C2S, C0-2 angle, T1S, C2-7 angle (CL) and T1S-CL, showed no significant differences in the measurements between the two modalities. Based on the DR images, OI was related to OT (r = .386, P < .01), C2S (r = .505, P < .01), CL (r = -.412, P < .01), and T1S-CL (r = .320, P < .05), and OI was matched with CL (r2 = .170) and T1S-CL (r2 = .102). Based on MRI images, OI was related to OT (r = .433, P < .01), C2S (r = .516, P < .01), CL (r = -.355, P < .01), and T1S-CL (r = .271, P < .05), and OI matched with C2-7 (r2 = .126) and T1S-CL (r2 = .073). CONCLUSION: OI is an independent parameter related to cervical anatomy and its measurement is unaffected by external factors. In patients with CSM, odontoid parameters may effectively describe the sagittal alignment of the cervical spine on DR and MRI images.

Peptide-modified bioresponsive chondroitin sulfate micelles for targeted doxorubicin delivery in triple-negative breast cancer.

Triple-negative breast cancer is an offensive tumor that is highly challenging to cure. In this study, we developed novel polymeric nanoparticles that target dual receptors and respond to reducing conditions for chemotherapeutic drug release in the treatment of triple-negative breast cancer. Then we synthesized and characterized a targeted peptide-grafted chondroitin sulfate A-ss-deoxycholic acid (TCSSD) copolymer and prepare doxorubicin (DOX)-loaded TCSSD (TCSSD-D) micelles high-loading content. The bioresponsive drug release of TCSSD-D nanoparticles was demonstrated in a glutathione-containing phosphate buffer solution. We found that TCSSD-D effectively targeted CD44 and P-selectin receptors both in vitro and in vivo. TCSSD-D micelles were higher cytotoxicity and cellular uptake than unmodified DOX-containing micelles in MDA-MB-231 cells. Furthermore, TCSSD-D micelles showed the strongest suppression of tumor growth among three DOX-based formulations in triple-negative MDA-MB-231-bearing nude mice. These results suggest that amphiphilic TCSSD nanoparticles can serve as a targeted and intelligent delivery vehicle for triple-negative breast cancer therapy.

Artificial cells delivering itaconic acid induce anti-inflammatory memory-like macrophages to reverse acute liver failure and prevent reinjury.

Hepatic macrophages represent a key cellular component of the liver and are essential for the progression of acute liver failure (ALF). We construct artificial apoptotic cells loaded with itaconic acid (AI-Cells), wherein the compositions of the synthetic plasma membrane and surface topology are rationally engineered. AI-Cells are predominantly localized to the liver and further transport to hepatic macrophages. Intravenous administration of AI-Cells modulates macrophage inflammation to protect the liver from acetaminophen-induced ALF. Mechanistically, AI-Cells act on caspase-1 to suppress NLRP3 inflammasome-mediated cleavage of pro-IL-1ß into its active form in macrophages. Notably, AI-Cells specifically induce anti-inflammatory memory-like hepatic macrophages in ALF mice, which prevent constitutive overproduction of IL-1ß when liver reinjury occurs. In light of AI-Cells' precise delivery and training of memory-like hepatic macrophages, they offer promising therapeutic potential in reversing ALF by finely controlling inflammatory responses and orchestrating liver homeostasis, which potentially affect the treatment of various types of liver failure.

Polyethylene glycol-modified pigment epithelial-derived factor: new prospects for treatment of retinal neovascularization.

Pathological retinal neovascularization and choroidal neovascularization are major causes of vision loss in a variety of clinical conditions, such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy. Pigment epithelial-derived factor (PEDF) has been found to be the most potent natural, endogenous inhibitor of neovascularization, but its application is restricted because of its instability and short half-life. Polyethylene glycol (PEG) has been used as a drug carrier to slow clearance rate for decades. The present study investigated PEGylated-PEDF for the first time and evaluated its long-term effects on preventing angiogenesis in vitro and in vivo. PEG showed lower cytotoxicity to human umbilical vein endothelial cells (HUVECs). In vitro, PEGylated-PEDF inhibited HUVEC proliferation, migration, tube formation, and vascular endothelium growth factor secretion and induced HUVEC apoptosis in a dose-dependent manner, and it showed a statistically significant difference compared with the PEDF treatment group. In vivo, PEGylated-PEDF had a long-lasting effect in both plasma and retinal concentrations. In an oxygen-induced retinopathy model, one intravitreous injection of PEGylated-PEDF after mouse pups were moved into room air resulted in a significant difference in the inhibition of retinal neovascularization, which decreased the nonperfusion area, compared with the PEDF-treated group. Our present study demonstrated for the first time the long-term inhibitory effects of PEGylated-PEDF on the prevention of neovascularization in vitro and in vivo. These data suggest that PEGylated-PEDF could offer an innovative therapeutic strategy for preventing retinal neovascularization.

Cucurbit[10]uril-mediated Supramolecular Assembly for Optically Tunable Dimers and Near White-light Emissive Materials.

Cucurbit[10]uril (Q[10]), the cucurbit[n]uril with a large cavity, exhibits several new features in the development of the host-guest complex. Thus, based on Q[10] and π-conjugated molecule, oligo(p-phenylenevinylene) derivative (OPVCOOH), the host-guest complexes with three different interaction ratios of 1 : 2, 2 : 2, and 3 : 2 assemblies (Q[10]: guest) were fabricated. Depending on the host/guest ratio, the emission color of these complexes ranged from blue to yellow-green. The extra Fe2+ coordinated with a bare carboxyl group of the Q[10]-OPVCOOH (3 : 2) assembly, obstructing its rotaxane structure and forming Q[10]-OPVCOOH-Fe2+ assembly, which may be used as a coating for near-white LED bulbs.

Cardiac safety analysis of first-line chemotherapy drug pegylated liposomal doxorubicin in ovarian cancer.

Pegylated liposomal doxorubicin (PLD) is a nano-doxorubicin anticancer agent. It was used as early as 2014 to treat ovarian and breast cancer, multiple myeloma and Kaposi's sarcoma. The 2018 National Comprehensive Cancer Network guidelines listed PLD as first-line chemotherapy for ovarian cancer. PLD has significant anticancer efficacy and good tolerance. Although PLD significantly reduces the cardiotoxicity of conventional doxorubicin, its cumulative-dose cardiotoxicity remains a clinical concern. This study summarizes the high-risk factors for PLD-induced cardiotoxicity, clinical dose thresholds, and cardiac function testing modalities. For patients with advanced, refractory, and recurrent malignant tumors, the use of PLD is still one of the most effective strategies in the absence of evidence of high risk such as cardiac dysfunction, and the lifetime treatment dose should be unlimited. Of course, they should also be comprehensively evaluated in combination with the high-risk factors of the patients themselves and indicators of cardiac function. This review can help guide better clinical use of PLD.

[Cognitive investigation and analysis of space loss in children].

PURPOSE: To investigate the difference of parent's cognition of children's space loss and its influencing factors, to provide reference for children's oral health education, in order to reduce the incidence of malocclusion. METHODS: A self-designed questionnaire was used to investigate the basic information and related problems of 36 parents whose children received space loss treatment. SPSS 22.0 software package was used for statistical analysis. RESULTS: Parents paid more attention to the common oral problems of their children, the awareness of oral prevention and health care were weak, the attention to treatment was higher than that of prevention. The attitude of parents to the cognition and targeted treatment of malocclusion caused by space loss was low(27.78%), which was significantly different from that of caries (75.00%) and premature loss of deciduous teeth (63.89%). The total cognition of space loss was 61.11%. The cognitive degree of parents with different characteristics was different: the cognitive degree of parents over 50 years old was lower(14.29%), the cognitive degree of parents with higher education was higher(82.35%), there was no significant difference in cognitive degree among different gender, occupation and family monthly income groups. Parents paid more attention to the basic oral health of their children, most of the interval time between this visit and the last visit was 3 months(63.89%). The main purpose of the visit was caries or tooth pain caused by caries(63.89%). Most of parents did not know the harmful effect of space loss(72.22%). There were more parents who did not know the necessity of treatment to space loss(58.33%). Parents mainly learned the treatment to space loss through the doctor's education during dental visits(72.22%). The number of active visits were less when space loss occured(22.22%), and most of parents were recommended by dentist when they came to the clinics(72.22%). Most parents were able to accept the dentists' advice on the treatment of space loss(77.78%). CONCLUSIONS: It is necessary to strengthen the propaganda, coverage and depth of oral health education care, strengthen the awareness of oral preventive health care, especially for the parents with special personality on the importance of space loss, to prevent primary teeth caries and premature loss of primary teeth, avoid the loss of dental space, make the complete primary dentition to form a normal permanent dentition.

[The effect of chronic kidney disease on periodontitis-related microorganisms in mice].

PURPOSE: To explore the effect of chronic kidney disease on the composition of oral microbial community in mice and find the significant species. METHODS: Twenty C57BL/6 male mice were randomly divided into 4 groups: healthy control group (HC), periodontitis group (PD), chronic kidney disease group (CKD) and chronic kidney disease and periodontitis group (CKD+PD). The periodontitis model was created in the fourth week when the chronic kidney disease model was established, and then the mice were sacrificed in the sixth week. Histopathological analysis of the kidney was performed by H-E staining and Masson's trichrome staining. Alveolar bone resorption of maxilla was analyzed by micro-CT analysis. The third-generation full-length sequencing of 16SrRNA gene was used to analyze the composition of oral microbial community among groups. Statistical analysis was performed using SPSS 24.0 software package. RESULTS: There were significant differences in alveolar bone resorption, the richness of species and the overall composition of the microbial community among the four groups (P＜0.001). In CKD group, Streptococcus azizii had the most significant abundance. Escherichia coli was the most significantly different species among identifiable bacteria in CKD+PD group, while Staphylococcus lentus and Lactobacillus murinus were species with the most significant differences in HC group and PD group, respectively. CONCLUSIONS: The composition of the oral microbial community was significantly different among four groups with significant species.