Epidemiological analysis of drinking water-type fluorosis areas and the impact of fluorosis on children's health in the past 40 years in China.

This study analyzed the effect of China's fluorosis prevention and control program, which has been in effect for more than 40 years, and the impact of fluorosis on children's health. Relevant research studies were retrieved from the following online databases from the time of their inception to May 2022: PubMed, ScienceDirect, Embase, Cochrane, China National Knowledge Infrastructure, and Wanfang. The Review Manager 5.3 software was used in statistical analyses. This article included seventy studies: Thirty-eight studies reported the effect of improving water quality and reducing fluoride content, the incidence rate of dental fluorosis in children, and the level of urinary fluoride, and thirty-two studies reported the intelligence quotient (IQ) and health status of children. Following water improvement strategies, the fluoride levels in drinking water decreased significantly; urinary fluoride levels and dental fluorosis decreased significantly in children. With regard to the effect of fluorosis on the IQ of children, the results showed that the IQ of children in areas with a high fluoride of fluorosis was lesser than that in areas with a low fluoride, and this difference was significant. Based on the prevalence of dental fluorosis and its effect on the intelligence of children, it appears that reducing fluoride levels in drinking water and monitoring water quality are important strategies for the prevention and treatment of fluorosis.

Ultrastable Zinc Anode by Simultaneously Manipulating Solvation Sheath and Inducing Oriented Deposition with PEG Stability Promoter.

Aqueous zinc-ion batteries are a low-cost and safe energy storage system, but suffer from detrimental side reactions and Zn dendrites due to the strong interactions between Zn2+ and water molecules in the electrolytes, and random Zn2+ deposition on the anode surface. Here, an electrolyte involving a dual-functional additive of polyethylene glycol (PEG) to bypass these issues is reported. The electrolyte can not only tailor the solvation sheath of Zn2+ but also enable favorably oriented deposition of Zn2+ on the anode surface. The dendrite-free Zn anode in Zn//Zn cells is obtained with high Columbic efficiency (98.8%) and long cycling lifespan (1500 h), six times longer than that of electrolyte without PEG at 0.25 mA cm-2 . What is more, the excellent cycling stability of the prepared batteries (Zn//V2 O5 ·1.6 H2 O) suggests that the developed tailoring strategy may propel a promising pathway for stabilizing Zn metal anodes.

Phosphorylated PAMAM dendrimers: an analog of dentin non-collagenous proteins, enhancing the osteo/odontogenic differentiation of dental pulp stem cells.

OBJECTIVES: Polyamidoamine (PAMAM) dendrimers have well-defined structures, with monodispersity and easily modified surface groups, and they have broad applications in biomedicine. In this study, phosphorylated PAMAM (P-PAMAM) dendrimers were synthesized based on the idea of mimicking the phosphorylated proteins of dentin non-collagenous proteins (DNCP). Then, proliferation and osteo/odontogenic differentiation effects of P-PAMAM on dental pulp stem cells (DPSCs) were investigated and were compared with DNCP. MATERIALS AND METHODS: P-PAMAM was synthesized via the Mannich-type reaction. DNCP were extracted directly from human dentin with ethylenediaminetetraacetic acid (EDTA) solution. Then, the conditioned medium of P-PAMAM and DNCP were prepared respectively and applied to DPSCs. Proliferation of P-PAMAM was investigated with CCK-8, flow cytometry, and EdU test. Osteo/odontogenic differentiation of P-PAMAM was analyzed using alkaline phosphatase activity and staining, RT-PCR, western blot, alizarin red staining, and immunofluorescence staining. RESULTS: Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance revealed that PAMAM were successfully phosphorylated. Western blot verified that the extracted DNCP contained dentin-related proteins DSPP, OPN, and BMP2. In cell proliferation, there was no apparent difference between P-PAMAM, DNCP, and Control groups (P > 0.05). P-PAMAM and DNCP upregulated related genes and proteins expression (DSPP/DSPP, COL-1/COL-1, ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN) and matrix mineralization. Still, the potential was lower than that of DNCP (P < 0.05). CONCLUSIONS: P-PAMAM dendrimers, as a biomimetic analog of DNCP, promote osteo/odontogenic differentiation of DPSCs without influencing their proliferation at a low concentration. CLINICAL RELEVANCE: This preliminary study about P-PAMAM dendrimers is expected to provide a more convenient bioactive macromolecular material for the regeneration of the pulp-dentin complex.

Application of the polystyrene model made by 3-D printing rapid prototyping technology for operation planning in revision lumbar discectomy.

OBJECTIVE: The objective was to evaluate the effectiveness of 3-D rapid prototyping technology in revision lumbar discectomy. 3-D rapid prototyping technology has not been reported in the treatment of revision lumbar discectomy. METHODS: Patients with recurrent lumbar disc herniation who were preparing to undergo revision lumbar discectomy from a single center between January 2011 and 2013 were included in this analysis. Patients were divided into two groups. In group A, 3-D printing technology was used to create subject-specific lumbar vertebral models in the preoperative planning process. Group B underwent lumbar revision as usual. Preoperative and postoperative clinical outcomes were compared between groups included operation time, perioperative blood loss, postoperative complications, Oswestry Disability Index (ODI), Japan Orthopaedics Association (JOA) scores, and visual analogue scale (VAS) scores for back pain and leg pain. RESULTS: A total of 37 patients were included in this study (Group A = 15, Group B = 22). Group A had a significantly shorter operation time (106.53 ± 11.91 vs. 131.92 ± 10.81 min, P < 0.001) and significantly less blood loss (341.67 ± 49.45 vs. 466.77 ± 71.46 ml, P < 0.001). There was no difference between groups for complication rate. There were also no differences between groups for any clinical metric. CONCLUSION: Using the 3-D printing technology before revision lumbar discectomy may reduce the operation time and the perioperative blood loss. There does not appear to be a benefit to using the technology with respect to clinical outcomes. Future prospective studies are needed to further elucidate the efficacy of this emerging technology.

Pyrene-based sulfonated organic porous materials for rapid adsorption of cationic dyes in water.

Porous organic polymers (POP) have gained attention because of their high specific surface area, porosity and their simplicity in synthesis, but for the most part, they are hydrophobic because of their organic backbone, making it difficult to expand their applications. Here, we have obtained poly(pyrene) porous organic polymers (PyPOP) through the polymerization of pyrene monomers catalysed by aluminium trichloride, which is a simple and inexpensive synthesis method. The sulfonated poly(pyrene) porous organic polymers (PyPOP-SO3H) obtained showed rapid adsorption of cationic dyes, especially malachite green (MG adsorption 1607 mg/g) and methylene blue (MB adsorption 1220 mg/g) in pH = 7 aqueous solution, room temperature. The results show that the Freundlich model is more in line with the adsorption process than the Langmuir model, whether for methylene blue or malachite green. In addition, the PSO kinetic model fits better than PFO kinetic model, whether it is for the adsorption of methylene blue or malachite green. The excellent adsorption performance of PyPOP-SO3H for cationic dyes may be due to the introduction of sulfonic acid groups, which not only increases the specific surface area but also allows better dispersion in water, increasing contact points and adsorption efficiency. This research expands the scope of exploration and application of POP.

Exploration of the SIRT1-mediated BDNF-TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis.

Introduction: Fluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF-TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments. Methods: This study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting. Results: All rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities. Discussion: Currently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.

Loofah Sponge-Derived Hygroscopic Photothermal Absorber for All-Weather Atmospheric Water Harvesting.

The loofah gourd is like a natural water tank that stores underground water and drains it out after aging, leaving only a three-dimensional network consisting of hollow and interconnected fibers. This phenomenon inspired us to fabricate a solar-energy-powered sorption-based atmospheric water harvesting device using a loofah sponge. Herein, moisture absorption and photothermal conversion strategies are rationally designed to fast release the absorbed water. This is accomplished by filling the hollow and connected loofah fiber with LiCl and replacing the original luffa peel with a bacterial cellulose (BC)/carbon nanotube (CNT) photothermal conversion membrane. As a result, loofah/BC/CNT (LBC)@LiCl presents a high water absorption capacity of 2.65 g g-1 at 90% relative humidity (RH) and fast water release performance of 1.33 kg m-2 h-1 under 1.0 sun. Noticeably, ∼1.92-2.40 kg LBC@LiCl can produce daily drinking water for adults (2000-2500 mL) in one night outdoors at ∼66% RH, proving that it is a feasible method to overcome the drinking water shortage of poor and arid areas using cheap and renewable biomass material.

Comparison between two pedicle screw augmentation instrumentations in adult degenerative scoliosis with osteoporosis.

BACKGROUND: The operative treatment of adult degenerative scoliosis combined with osteoporosis increase following the epidemiological development. Studies have confirmed that screws in osteoporotic spines have significant lower-screw strength with more frequent screw movements within the vertebra than normal spines. Screws augmented with polymethylmethacrylate (PMMA) or with autogenous bone can offer more powerful corrective force and significant advantages. METHODS: A retrospective analysis was conducted on 31 consecutive patients with degenerative lumbar scoliosis combined with osteoporosis who had surgery from December 2000. All had a minimum of 2-year follow-up. All patients had posterior approach surgery. 14 of them were fixed with pedicle screw by augmentation with polymethylmethacrylate (PMMA) and the other 17 patients with autogenous bone. Age, sex and whether smoking were similar between the two groups. Surgical time, blood loss, blood transfusion, medical cost, post surgery ICU time, hospital day, length of oral pain medicines taken, Pre-and postoperative Oswestry disability index questionnaire and surgical revision were documented and compared. Preoperative, postoperative and final follow up Cobb angle, sagittal lumbar curve, correction rate, and Follow up Cobb loss were also compared. RESULTS: No significant differences were found between the autogenous bone group and polymethylmethacrylate group with regards to all the targets above except for length of oral pain medicines taken and surgery cost. 2 patients were seen leakage during operation, but there is neither damage of nerve nor symptom after operation. No revision was needed. CONCLUSION: Both augmentation pedicle screw with polymethylmethacrylate (PMMA) and autogenous bone treating degenerative lumbar scoliosis combined with osteoporosis can achieve a good surgical result. Less oral pain medicines taken are the potential benefits of polymethylmethacrylate augmentation, but that is at the cost of more medical spending.

The Correlation Between the Diffusion Coefficient of Bone Cement and Efficacy in Percutaneous Vertebroplasty.

This study investigated the effect of bone mineral density (BMD) on the diffusion coefficient (DC) of bone cement in percutaneous vertebroplasty (PVP) and the correlation between the DC and the efficacy after PVP. This was a retrospective study of PVP cases with follow-up longer than 12 months. The cases were assigned to 3 groups according to the BMD: BMD decrease group, osteoporosis group, and severe osteoporosis group. The 3 groups were compared regarding bone cement injection volume (IV), diffusion volume (DV), DC, visual analog scale (VAS) score, Oswestry Disability Index (ODI) score, and vertebral height loss ratio (VHLR). The correlation between DC and BMD, IV, DV, and VHLR was analyzed. The least significant difference test was used for comparison among the 3 groups, and the Pearson correlation coefficient was used for correlation analysis. There were a total of 132 cases, including 34 males and 98 females with a mean age of 76.5±9.6 years. The DV was larger than the IV in each group (P<.05). There was no statistically significant difference in the IV, VAS score, and ODI among the 3 groups (P>.05). However, there were significant differences in the DC and VHLR among the 3 groups (P<.05). Correlation analysis showed that there were significant correlations between BMD and IV (-0.716), BMD and DC (0.754), IV and DV (0.502), and IV and DC (-0.666) (P<.01). Scatter plot showed that the correlation between IV and BMD was r=0.716, R2=0.513, and the correlation between DC and BMD was r=0.754, R2=0.568. The DV was larger than the IV in PVP, and BMD was closely related to the DC. The higher the BMD, the higher the DC. Short-term follow-up revealed that the DC was inversely proportional to the VHLR. [Orthopedics. 2021;44(1):e95-e100.].

Highly selective and sensitive chemiluminescence biosensor for adenosine detection based on carbon quantum dots catalyzing luminescence released from aptamers functionalized graphene@magnetic ß-cyclodextrin polymers.

In this work, a highly selective and sensitive chemiluminescence (CL) biosensor was prepared for adenosine (AD) detection based on carbon quantum dots (CQDs) catalyzing the CL system of luminol-H2O2 under alkaline environment and CQDs was released from the surface of AD aptamers functionalized graphene @ magnetic ß-cyclodextrin polymers (GO@Fe3O4@ß-CD@A-Apt). Firstly, GO@Fe3O4@ß-CD and CQDs were prepared and characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM), UV-Vis absorption spectra (UV), fluorescence spectra (FL), fourier transform infrared (FTIR) and X-ray powder diffraction (XRD). For GO@Fe3O4@ß-CD, Fe3O4 was easy to separate, GO had good biocompatibility and large specific surface area, and ß-CD further increased the specific surface area of the adenosine polymers (A-Apt) to provided larger binding sites to A-Apt. Then, A-Apt was modified on the surface of GO@Fe3O4@ß-CD while CQDs was modified by ssDNA (a single stranded DNA partially complementary to A-Apt). The immobilization property (GO@Fe3O4@ß-CD to A-Apt) and the adsorption property (GO@Fe3O4@ß-CD@A-Apt to CQDs-ssDNA) were sequentially researched. The base-supported chain-like polymers - GO@Fe3O4@ß-CD@A-Apt/CQDs-ssDNA was successfully obtained. When AD existed, CQDs-ssDNA was released from the surface of GO@Fe3O4@ß-CD@A-Apt and catalyzed CL. After that, under optimized CL conditions, AD could be measured with the linear concentration range of 5.0 × 10-13-5.0 × 10-9 mol/L and the detection limit of 2.1 × 10-13 mol/L (3δ) while the relative standard deviation (RSD) was 1.4%. Finally, the GO@Fe3O4@ß-CD@A-Apt/CQDs-ssDNA-CL biosensor was used for the determination of AD in urine samples and recoveries ranged from 98.6% to 101.0%. Those satisfactory results illustrated the proposed CL biosensor could achieve highly selective, sensitive and reliable detection of AD and revealed potential application for AD detection in monitoring and diagnosis of human cancers.

Randomized, Double-Blind, Placebo-Controlled Trial of Shuanghua Baihe Tablets to Prevent Oral Mucositis in Patients With Nasopharyngeal Cancer Undergoing Chemoradiation Therapy.

PURPOSE: Oral mucositis is a common unpreventable complication associated with chemoradiation therapy. Shuanghua Baihe tablets have been approved by the Chinese Food and Drug Administration for treating recurrent oral mucosa ulceration. This study assessed whether Shuanghua Baihe tablets could prevent oral mucositis during chemoradiation therapy for locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: This multicenter, randomized, double-blind, placebo-controlled trial was conducted at 11 hospitals in China between January 22, 2014, and September 21, 2015. Eligible patients (N=240, 18-70 years old) with pathologically diagnosed locally advanced nasopharyngeal carcinoma were randomly assigned (computer-block randomization; 1:1) to receive Shuanghua Baihe tablets or a placebo (4 tablets, 3 times a day, for 7 weeks) at the initiation of chemoradiation therapy. Administration of Shuanghua Baihe tablets could be ended if grade 3 or higher oral mucositis developed and patients were unwilling to continue taking the drug. The primary endpoints were oral mucositis incidence and latency. RESULTS: The incidence of oral mucositis during this study was significantly lower in the Shuanghua Baihe group (85.0%; 95% confidence interval [CI], 78.6%-91.4%) than in the placebo group (96.6%; 95% CI, 93.4%-99.9%; P=.0028). The median latency period was 28 days in the Shuanghua Baihe group and 14 days in the placebo group (hazard ratio, 0.17; 95% CI, 0.12-0.23; P<.0001). Compared with placebo, Shuanghua Baihe tablets significantly reduced the oral mucositis severity scores recorded by the investigators (Oral Mucositis Score, 24.0 [range, 0.0-67.8] vs 57.5 [range, 0.0-98.0]; P<.0001), full-time nurses (Oral Assessment Guide score, 462.0 [range, 392.0-664.7] vs 520.4 [range, 392.0-714.0]; P<.0001), and patients (score for soreness of mouth and throat, 4.0 [range, 0-10] vs 6.0 [range, 0-10]; P<.0001). No serious adverse events were observed, and the incidence of mild or moderate gastrointestinal adverse events associated with Shuanghua Baihe tablets was 3.3%. The short-term response rate was similar in patients receiving Shuanghua Baihe tablets and those receiving placebo during chemoradiation therapy during this study. CONCLUSIONS: Shuanghua Baihe tablets reduced the occurrence, latency, and severity of oral mucositis in patients with nasopharyngeal cancer during chemoradiation therapy treatment.

Local in vitro delivery of rapamycin from electrospun PEO/PDLLA nanofibers for glioblastoma treatment.

Rapamycin, a mammalian target of rapamycin inhibitor and anti-proliferative agent, is used to treat glioma and other malignancies, but its effectiveness is limited by the fact that it cannot be delivered in a targeted manner to the site of the tumor. To address this issue, we fabricated a mesh via electrospinning using two biodegradable materials, poly(lactic acid) (PLA) and polyethylene oxide (PEO) as a carrier for rapamycin delivery to the tumor. Nanofiber diameter decreased with increasing PLA concentration in the mixed solution. Scanning electron microscopy analysis revealed the smooth and uniform surface morphology of hybrid fibers. Fourier transform infrared spectroscopy analysis demonstrated that rapamycin was encapsulated in the polymer solution; encapsulation efficiency was high and stable over the range of drug concentrations from 0.5-2wt%. A correlation was observed between sustained release of the drug in vitro and cytotoxicity in cultured glioma cells. These results indicate that the PEO/poly(d,l-lactic acid) nanofiber mesh can be used as a targeted delivery system for rapamycin that can limit side effects and prevent locoregional recurrence following surgical resection of glioma.

New oral linguiform projections and their associated neurons in the third-stage infective larva of the parasitic nematode Oesophagostomum dentatum.

The infective larvae (L3i) of the nematode parasite of swine, Oesophagostomum dentatum, are passively ingested by their hosts. The L3i exhibit certain behaviors that are probably selected to increase the likelihood of ingestion, by strategic positioning in the environment. The larvae show positive geotactic behavior and respond to temperature variations in their environment, as shown by their behavior on a thermal gradient. To investigate neuronal control of this behavior, we initiated a study of the structure of the amphidial neurons of this parasite. The same number and types of neuronal dendritic processes are found in the amphids of the O. dentatum L3i as in those of its close relatives Haemonchus contortus and Ancylostoma caninum. Well-developed dendritic processes of wing cells are located in the amphidial sheath cells, these being similar to wing cells AWA in the free-living nematode Caenorhabditis elegans but actually more extensive. Similar to its close relatives just mentioned, and C. elegans as well, O. dentatum L3i has prominent finger cell processes, the finger cell neurons being the thermoreceptors in all 3 of the preceding species. However, unlike the arrangement seen in H. contortus and A. caninum, where the microvilli-like "fingers" of these neurons lie dorsal to the amphidial channel and occupy a very large portion (>50%) of the anterior end of the larva, the dendritic process of the finger cells in O. dentatum extends into unusual linguiform projections that, in turn, extend into the lumen of the mouth tube, a complex structural arrangement that has not been described for any other nematode.

Anti-Neoplastic Cytotoxicity of SN-38-Loaded PCL/Gelatin Electrospun Composite Nanofiber Scaffolds against Human Glioblastoma Cells In Vitro.

Electrospun poly(ε-caprolactone) (PCL)/gelatin (GT) scaffolds were developed to provide controlled release of 7-ethyl-10-hydroxy camptothecin (SN-38). Acetic acid was introduced to improve the miscibility of PCL and GT to produce a homogeneous nanofiber membrane mixture. The effect of SN-38 content in binary mixtures on processability, fiber morphology, water sorption, swelling, and drug release was investigated. Electrospun PCL/GT blend nonwoven fibers showed fiber surface roughness, decreased PCL crystallinity, and increased swelling with increasing drug content of 1, 2, and 4 wt %. Additionally, increasing the SN-38 concentration reduced the degradation rate of the GT. Furthermore, we hypothesize the existence of a drug content saturation point in the monoaxial fiber to explain the different drug release patterns of PG2 compared with those of PG1 and PG4. The matrix also showed good biodegradation and anti-tumor function. Our results demonstrate that SN-38-loaded PCL/GT fibers can be obtained by electrospinning. The SN-38-loaded fibers merit further evaluation as a means to potentially prevent locoregional recurrence following surgical tumor resection.

The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma.

Immunoliposomes (ILs) anchored with internalizing human antibodies capable of targeting all subtypes of mesothelioma can be useful for targeted imaging and therapy of this malignant disease. The objectives of this study were to evaluate both the in vitro and in vivo tumor targeted internalization of novel internalizing human single chain antibody (scFv) anchored ILs on both epithelioid (M28) and sarcomatoid (VAMT-1) subtypes of human mesothelioma. ILs were prepared by post-insertion of mesothelioma-targeting human scFv (M1) onto preformed liposomes and radiolabeled with (111)In ((111)In-IL-M1), along with control non-targeted liposomes ((111)In-CL). Incubation of (111)In-IL-M1 with M28, VAMT-1, and a control non-tumorigenic cell line (BPH-1) at 37 °C for 24 h revealed efficient binding and rapid internalization of ILs into both subtypes of tumor cells but not into the BPH-1 cells; internalization accounted for approximately 81-94% of total cell accumulation in mesothelioma cells compared to 37-55% in control cells. In tumor-bearing mice intravenous (i.v.) injection of (111)In-IL-M1 led to remarkable tumor accumulation: 4% and 4.7% injected dose per gram (% ID/g) for M28 and VAMT-1 tumors, respectively, 48 h after injection. Furthermore, tumor uptake of (111)In-IL-M1 in live xenograft animal models was verified by single photon emission computed tomography (SPECT/CT). In contrast, i.v. injection of (111)In-CL in tumor-bearing mice revealed very low uptake in both subtypes of mesothelioma, 48 h after injection. In conclusion, M1 scFv-anchored ILs showed selective tumor targeting and rapid internalization into both epithelioid and sarcomatoid subtypes of human mesothelioma, demonstrating its potential as a promising vector for enhanced tumor drug targeting.

Clinical characteristics and treatment of severe encephalitis associated with neurogenic pulmonary edema caused by enterovirus 71 in China.

BACKGROUND: Hand-foot-mouth disease has become a major public health issue in children in China. In the present prospective study we investigated the clinical characteristics and emergency management of children with severe encephalitis associated with NPE caused by enterovirus 71. METHODS: The study was conducted in 2 pediatric intensive care units (PICUs) over a 2-month period. Clinical records were reviewed of critically ill children with severe encephalitis associated with NPE caused by EV71 who were admitted to PICUs during the period of May to June 2008 in Fuyang. RESULTS: We reviewed the complete records of 36 children, of whom 23 (63.9%) were male and 13 (36.1%) female. Their age ranged from 4 to 48 months, with an average of 15.8 months. All children except one were under 3 years of age. The overall mortality in these children was 19.4%. The average duration of critical life threatening signs and symptoms was 2.1 days (12 hours-5 days). Nervous system diseases included brainstem encephalitis in 27 children (75%), brainstem encephalitis associated with myelitis in 6 children (16.7%), and general encephalitis in 3 chidren (8.3%), respectively. In 12 patients of NPE (33.3%) pink or bloody bubble sputum and asymmetric pulmonary edema or hemorrhage was the primary manifestation but no typical exanthema was observed. Five children died of acute onset of NPE and / or pulmonary hemorrhage with rapid progression of cardiopulmonary failure within hours after admission. Therapeutic management consisted of mechanical ventilation and administration of mannitol, methylprednisolone, intravenous immunoglobulin (IVIG) and vasoactive drugs, associated with the need of fluid volume resuscitation in 9 (25%) of the 36 children. CONCLUSIONS: In children less than 3 years of age found to be affected by severe EV71 encephalitis associated with NPE, one fifth may die. The major organ systems infected by severe EV71 include the central nervous system, the respiratory system, and the cardiovascular system. Early diagnosis and evaluation, respiratory support, treatment of intracranial hypertension, and mainttenance of function of the cardiovascular system are the most important therapeutic measures.

Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects.

PURPOSE: To investigate the role of macrophages in tumor progression under sorafenib treatment and to explore whether combination of drugs that deplete macrophages improved the antitumor effect of sorafenib. EXPERIMENTAL DESIGN: Tumor growth, lung metastasis, and tumor angiogenesis were observed in HCCLM3-R and SMMC7721, two human hepatocellular carcinoma xenograft nude mouse models, when treated with sorafenib (30 mg/kg daily, n = 6 per group) or a vehicle as control. Macrophage infiltration was measured in the peripheral blood and in sorafenib-treated tumor by immunohistochemistry and flow cytometry with F4/80 antibody and CD11b antibody. The effect of macrophage depletion on tumor angiogenesis and metastasis after sorafenib treatment, using two drug target macrophages, zoledronic acid (ZA) and clodrolip, was measured in the two models of hepatocellular carcinoma. RESULTS: Although sorafenib significantly inhibited tumor growth and lung metastasis, it induced a significant increase in peripheral recruitment and intratumoral infiltration of F4/80- and CD11b-positive cells, which was accompanied with elevation of colony-stimulating factor-1, stromal-derived factor 1alpha, and vascular endothelial growth factor in the tumor and elevation of plasma colony-stimulating factor-1 and mouse vascular endothelial growth factor in peripheral blood, suggesting the role of macrophages in tumor progression under sorafenib treatment. Depletion of macrophages by clodrolip or ZA in combination with sorafenib significantly inhibited tumor progression, tumor angiogenesis, and lung metastasis compared with mice treated with sorafenib alone. ZA was more effective than clodrolip. CONCLUSIONS: Macrophages may have an important role in tumor progression under sorafenib treatment. ZA is promising when combined with sorafenib to enhance its antitumor effect.