Prevalencia de osteopenia del prematuro antes y después de la implementación de una estrategia temprana de manejo fosfocálcico / Prevalence of osteopenia of prematurity before and after implementing an early strategy with the use of calcium and phosphate

Introducción. Con el uso de la nutrición parenteral agresiva en recién nacidos de muy bajo peso, se detectaron alteraciones del metabolismo fosfocálcico. En 2016 se implementó una estrategia de prevención a través del monitoreo fosfocálcico y su suplementación temprana. El objetivo fue estudiar si esta estrategia disminuye la prevalencia de osteopenia e identificar factores de riesgo asociados. Población y métodos. Estudio cuasiexperimental que comparó la prevalencia de osteopenia entre dos grupos: uno después de implementar la estrategia de monitoreo y suplementación fosfocálcica (01/01/2017-31/12/2019), y otro previo a dicha intervención (01/01/2013-31/12/2015). Resultados. Se incluyeron 226 pacientes: 133 pertenecen al período preintervención y 93 al posintervención. La prevalencia de osteopenia global fue del 26,1 % (IC95% 20,5-32,3) y disminuyó del 29,3 % (IC95% 21,7-37,8) en el período preintervención al 21,5 % (IC95% 13,6-31,2) en el posintervención, sin significancia estadística (p = 0,19). En el análisis multivariado, el puntaje NEOCOSUR de riesgo de muerte al nacer, recibir corticoides posnatales y el período de intervención se asociaron de manera independiente a osteopenia. Haber nacido luego de la intervención disminuyó un 71 % la probabilidad de presentar fosfatasa alcalina >500 UI/L independientemente de las restantes variables incluidas en el modelo. Conclusión. La monitorización y suplementación fosfocálcica precoz constituye un factor protector para el desarrollo de osteopenia en recién nacidos con muy bajo peso al nacer.

Introduction. With the use of aggressive parenteral nutrition in very low birth weight infants, alterations in calcium and phosphate metabolism were detected. In 2016, a prevention strategy was implemented through calcium phosphate monitoring and early supplementation. Our objective was to study whether this strategy reduces the prevalence of osteopenia and to identify associated risk factors. Population and methods. Quasi-experiment comparing the prevalence of osteopenia between two groups: one after implementing the calcium phosphate monitoring and supplementation strategy (01/01/2017­12/31/2019) and another prior to such intervention (01/01/2013­12/31/2015). Results. A total of 226 patients were included: 133 in the pre-intervention period and 93 in the post-intervention period. The overall prevalence of osteopenia was 26.1% (95% CI: 20.5­32.3) and it was reduced from 29.3% (95% CI: 21.7­37.8) in the pre-intervention period to 21.5% (95% CI: 13.6­31.2) in the post-intervention period, with no statistical significance (p = 0.19). In the multivariate analysis, the NEOCOSUR score for risk of death at birth, use of postnatal corticosteroids, and the intervention period were independently associated with osteopenia. Being born after the intervention reduced the probability of alkaline phosphatase > 500 IU/L by 71%, regardless of the other variables included in the model. Conclusion. Calcium phosphate monitoring and early supplementation is a protective factor against the development of osteopenia in very low birth weight infants.

Structural stability of Hib capsular polysaccharide in vaccine manufacturing / 中国生物制品学杂志

@#Objective To evaluate the stability of polyribosylribitol phosphate(PRP),the basic structure of capsular polysaccharide of Haemophilus influenzae type b(Hib),in the preparation of Hib conjugate vaccine.Methods The structures of the prepared Hib polysaccharides,polysaccharide derivatives and protein-conjugated polysaccharides were analyzed by nuclear magnetic resonance spectroscopy(NMR).Results The detection results of the prepared Hib polysaccharides,polysaccharide derivatives and protein-conjugated polysaccharides all met the requirements of relevant standards of Chinese Pharmacopoeia(VolumeⅢ,2020 edition),and the NMR spectra showed no significant change.Conclusion The basic structure PRP of the main carbohydrate antigen of Hib conjugate vaccine had no change during the vaccine manufacturing.

Mechanisms of brain damage caused by inorganic fluoride using proteomics-based techniques / 环境与职业医学

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L−1), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L−1), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg−1). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

3D Printing characteristics and mechanical properties of a bio scaffold obtained from a Micro-CT Scan, using the fused deposition modeling technique

The objective is to determine which biopolymer has the best 3D printing characteristics and mechanical properties for the manufacture of a bioscaffold, using the fused deposition printing technique, with models generated from an STL file obtained from a Micro-CT scan taken from a bovine iliac crest bone structure. Through an experimental exploratory study, three study groups of the analyzed biopolymers were carried out with thirteen printed structures of each one. The first is made of 100% PLA. The second, 90B, we added 1g of diatom extract, and the third, 88C, differs from the previous one in that it also contains 1g of calcium phosphate. The 39 printed structures underwent a visual inspection test, which required the fabrication of a gold standard scaffold in resin, with greater detail and similarity to the scanned bone structure. Finally, the structures were subjected to a compressive force (N) to obtain the modulus of elasticity (MPa) and compressive strength (MPa) of each one of them. A statistically significant difference (p=0.001) was obtained in the printing properties of the biomaterial 88C, compared to 90B and pure PLA and the 88C presented the best 3D printing characteristics. In addition, it also presented the best mechanical properties compared to the other groups of materials. Although the difference between these was not statistically significant (p=0.388), in the structures of the 88C biomaterial, values of compressive strength (8,84692 MPa) and modulus of elasticity (43,23615 MPa) were similar to those of cancellous bone in the jaws could be observed. Because of this result, the 88C biomaterial has the potential to be used in the manufacture of bioscaffolds in tissue engineering.

El objetivo es determinar cuál biopolímero presenta las mejores características de impresión 3D y propiedades mecánicas para la fabricación de un bioandamiaje, utilizando la técnica de impresión por deposición fundida, con modelos generados a partir de un archivo en formato STL que se obtuvo de un Micro-CT Scan de una estructura osea de cresta iliaca bovina. Mediante un estudio exploratorio, se realizaron 3 grupos de estudio con trece estructuras impresas de cada uno. El primero, se compone 100% de PLA. El segundo, 90B, se le agrega 1g de extracto de diatomea, y el tercero, 88C, se diferencia del anterior ya que contiene además, 1g de fosfato de calcio. A las 39 estructuras impresas se les realizó una prueba de inspección visual, por lo que se requirió la confección de un patrón de oro en resina, con mayor detalle y similitud a la estructura ósea escaneada. Finalmente, las estructuras fueron sometidas a una fuerza compresiva (N) para la obtención del módulo de elasticidad (MPa) y de la resistencia compresiva (MPa) de cada una de ellas. Se obtuvo una diferencia estadísticamente significativa (p=0,001) en las propiedades de impresión del biomaterial 88C, con respecto al 90B y al PLA puro, presentando las mejores características de impresión 3D. Además, obtuvo las mejores propiedades mecánicas en comparación con los otros grupos de materiales. Aunque la diferencia entre estos no fue estadísticamente significativa (p=0,388), en las estructuras del biomaterial 88C, se pudieron observar valores de resistencia compresiva (8,84692 MPa) y módulo de elasticidad (43,23615 MPa) que son semejantes a los del hueso esponjoso de los maxilares. A razón de este resultado, el biomaterial 88C cuenta con el potencial para ser utilizado en la fabricación de bioandamiajes en la ingeniería tisular.

Effect of Cyanobacterial Combinations on Peanut Yield

The characteristics of two cyanobacterial strains, Anabaena oryzae and Nostoc muscorum, were studied in order to use them as biofertilizers in a field experiment conducted in the two winter seasons of 2021 and 2022 at the Ismailia Agricultural Research Center Station to study the effect of both strains on peanut plant in sandy soil. Cyanobacterial strains were used individually by coating seed, soil drench, and foliar applications, as well as mixed applications of two strains in various ways. Both cyanobacterial strains morphological examination revealed that they both have heterocysts, nitrogen, phosphorus, and potassium in their culture filtrate, and they were able to produce chlorophyll a and phosphatase enzymes. The results of an agricultural experiment showed that using Nostoc muscorum and Anabaena oryzae separately had a positive effect on peanut plants in a variety of applications, but combining both of these applications with 75% nitrogen increased the growth traits, nutrient contents, and soil biological activities in both peanut plants and their rhizosphere soil. The soil drench treatment with A. oryzae and Nostoc muscorum plus 75% nitrogen produced the highest growth results and peanut yields in a single application. The A. oryzae Soil Drench Application (S) + N. muscorum Foliar Application (F) with 75% N reported the best outcomes in mixed treatments. However, compared to single applications, all blended applications displayed better growth and yield characteristics. The results of the study suggest that employing cyanobacteria in a mixed application will enhance its advantages over a single use.

Refractory Rickets

Nutritional rickets, caused by vitamin D and/or calcium deficiency is by far the most common cause of rickets. In resource-limited settings, it is therefore not uncommon to treat rickets with vitamin D and calcium. If rickets fails to heal and/or if there is a family history of rickets, then refractory rickets should be considered as a differential diagnosis. Chronic low serum phosphate is the pathological hallmark of all forms of rickets as its low concentration in extracellular space leads to the failure of apoptosis of hypertrophic chondrocytes leading to defective mineralisation of the growth plate. Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) control serum phosphate concentration by facilitating the excretion of phosphate in the urine through their action on the proximal renal tubules. An increase in PTH, as seen in nutritional rickets and genetic disorders of vitamin D-dependent rickets (VDDRs), leads to chronic low serum phosphate, causing rickets. Genetic conditions leading to an increase in FGF23 concentration cause chronic low serum phosphate concentration and rickets. Genetic conditions and syndromes associated with proximal renal tubulopathies can also lead to chronic low serum phosphate concentration by excess phosphate leak in urine, causing rickets. In this review, authors discuss an approach to the differential diagnosis and management of refractory rickets

Nuevas estrategias terapéuticas para tratar la hiperfosfatemia en la IRC: foco en la absorción intestinal / New therapeutic strategies to treat hyperphosphatemia in CRF: focus on intestinal absorption

RESUMEN El manejo de la hiperfosfatemia de los pacientes con insuficiencia renal crónica en diálisis permanece como un desafío. A pesar de utilizar un enfoque multifacético que incluye la restricción dietética, la remoción de fósforo por la diálisis y el uso de quelantes de fósforo, esta estrategia múltiple no logra reducir los niveles de fósforo en más de 2 mg/dl. El control de fósforo de los pacientes en diálisis es fundamental en razón de la relación monotónica entre los niveles séricos de fosfato y el incremento del riesgo cardiovascular. Por lo tanto, hay una necesidad de explorar nuevas estrategias para reducir los niveles séricos de fosfato a niveles normales. Recientes avances en nuestra compresión de los mecanismos que subyacen a la homeostasis del fósforo sugieren que el transporte gastrointestinal del fósforo podría ser un objetivo. Recientemente se han desarrollado inhibidores de los cotransportadores sodio fosfato del intestino y se ha revalorizado el uso de la nicotinamida, en su formulación de liberación prolongada, que también actuaria por ese mecanismo. También se han drogas como el tenapanor, que inhibiendo el intercambiador sodio/hidrogeno isoforma 3 del enterocito, disminuyen la absorción paracelular de fósforo.

ABSTRACT Management of hyperphosphatemia in patients with chronic renal failure on dialysis remains challenging. Despite using a multifaceted approach that includes dietary restriction, phosphorus removal by dialysis, and phosphate binders, these multiple strategies fail to reduce phosphorus levels by more than 2 mg/dL. Phosphorus control in dialysis patients is essential due to the monotonic relationship between serum phosphate levels and increased cardiovascular risk. Therefore, there is a need to explore new strategies to reduce serum phosphate levels to normal levels. Recent advances in understanding the mechanisms underlying phosphorus homeostasis suggest that the gastrointestinal transport of phosphorus could be a target. Inhibitors of intestinal sodium phosphate cotransporters recently developed, and using of nicotinamide, in its prolonged release formulation, which would also act by this mechanism, has been revalued. There have also been drugs such as tenapanor, which, by inhibiting the isoform three sodium/hydrogen exchanger of the enterocyte, decreases the paracellular absorption of phosphorus.

Metabolismo de los esfingolípidos y su relación con las enfermedades cardiovasculares, renales y metabólicas / Sphingolipid metabolism and its relationship with cardiovascular, renal and metabolic diseases

Resumen Los esfingolípidos (esfingomielina, glucolípidos y gangliósidos) se localizan en las membranas celulares, el plasma y las lipoproteínas. En pacientes con enfermedades cardiovasculares, renales y metabólicas, el perfil de los esfingolípidos y sus metabolitos (ceramida, esfingosina y esfingosina-1-fosfato) se modifica, y estos cambios pueden explicar las alteraciones en algunas respuestas celulares, como la apoptosis. Además, se ha sugerido que la esfingosina y la esfingosina-1-fosfato previenen la COVID-19. En esta revisión también se mencionan brevemente las técnicas que permiten el estudio de los esfingolípidos y sus metabolitos.

Abstract Sphingolipids (sphingomyelin, glycolipids, gangliosides) are located in cell membranes, plasma, and lipoproteins. In patients with cardiovascular, renal, and metabolic diseases, the profile of sphingolipids and their metabolites (ceramide, sphingosine, and sphingosine-1-phosphate) is modified, and these changes may explain the alterations in some cellular responses such as apoptosis. Furthermore, sphingosine and sphingosine-1-phosphate have been suggested to prevent COVID-19. This review also briefly mentions the techniques that allow us to study sphingolipids and their metabolites.

In vitro effect of low-fluoride toothpaste supplemented with sodium trimetaphosphate, xylitol, and erythritol on enamel demineralization

Abstract Regular use of toothpaste with fluoride (F) concentrations of ≥ 1000 ppm has been shown to contribute to reducing caries increment. However, when used by children during the period of dental development, it can lead to dental fluorosis. Objective: In this study, we aimed to evaluate the in vitro effect of a toothpaste formulation with reduced fluoride (F) concentration (200 ppm) supplemented with sodium trimetaphosphate (TMP: 0.2%), Xylitol (X:16%), and Erythritol (E: 4%) on dental enamel demineralization. Methodology: Bovine enamel blocks were selected according to initial surface hardness (SHi) and then divided into seven experimental toothpaste groups (n=12). These groups included 1) no F-TMP-X-E (Placebo); 2) 16% Xylitol and 4% Erythritol (X-E); 3) 16% Xylitol, 4% Erythritol and 0.2%TMP (X-E-TMP); 4) 200 ppm F (no X-E-TMP: (200F)); 5) 200 ppm F and 0.2% TMP (200F-TMP); 200 ppm F, 16% Xylitol, 4% Erythritol, and 0.2% TMP (200F-X-E-TMP); and 7) 1,100 ppm F (1100F). Blocks were individually treated 2×/day with slurries of toothpastes and subjected to a pH cycling regimen for five days (DES: 6 hours and RE: 18 hours). Then, the percentage of surface hardness loss (%SH), integrated loss of subsurface hardness (ΔKHN), fluoride (F), calcium (Ca), and phosphorus (P) in enamel were determined. The data were analyzed by ANOVA (1-criterion) and the Student-Newman-Keuls test (p<0.001). Results: We found that the 200F-X-E-TMP treatment reduced %SH by 43% compared to the 1100F treatments (p<0.001). The ΔKHN was ~ 65% higher with 200F-X-E-TMP compared to 1100F (p<0.001). The highest concentration of F in enamel was observed on the 1100F treatment (p<0.001). The 200F-X-E-TMP treatment promote higher increase of Ca and P concentration in the enamel (p<0.001). Conclusion: The association of 200F-X-E-TMP led to a significant increase of the protective effect on enamel demineralization compared to the 1100F toothpaste.

Research Progress on Correlation of Glucose Metabolism Mechanism with Invasion and Metastasis of Nasopharyngeal Carcinoma Cells / 肿瘤防治研究

Metastasis is the main cause of cancer-related death. Growing evidence has shown that changes in glucose metabolism in nasopharyngeal carcinoma cells affect the invasion and metastasis of nasopharyngeal carcinoma through many pathways. This review summarizes the molecular mechanism underlying abnormal glucose metabolism in nasopharyngeal carcinoma cells and analyzes its relationship with the invasion and metastasis of nasopharyngeal carcinoma, including aerobic glycolysis, aerobic oxidation, and pentose phosphate pathway. The aim is to provide novel approaches using the relationships among glucose metabolism, invasion, and metastasis in the targeted therapy of nasopharyngeal carcinoma.

The regulation of APGAT4 on the growth and lenvatinib resistance of hepatocellular carcinoma / 中华肝脏病杂志

Objective: To investigate the effect of 1-acyl-sn-glycerol-3-phosphate acyltransferaseδ (APGAT4) on the growth and lenvatinib resistance of hepatocellular carcinoma (HCC), and provide novel targets for HCC treatment. Methods: Using the bioinformatics methods to screen out upregulated genes in lenvatinib resistant cell lines from GEO dataset and survival related genes from TCGA dataset. Immumohistochemical staining was used to detect the expression AGPAT4 in HCC tissues, and its correlation with patients' survival. CCK8, EdU, cell cycle, and cell apoptosis assays were used to investigate the impact of role AGPAT4 on the proliferation and lenvatinib reistance of HCC cells. AGPAT4 stable knockdown cell line and subcutaneous nude mouse model were established to test the therapeutic effects of Lenvatinib. Analysis of variance was used to compare the differences between data sets. Results: APGAT4 was the common factor that predicted poor survival and Lenvatinib resistance. The mRNA and protein levels of APGAT4 were significantly upregulated in HCC tissues compared to the para-tumor tissues (P < 0.05). Using siRNA could significantly knocked down the mRNA and protein expression of APGAT4 in HCC cell lines Hep3B and HCCLM3. Compared with the control group, the proliferation ability of HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group was significantly inhibited, and the cell cycle was arrested in G2/M phase (P < 0.05). In addition, compared to the control group, HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group showed significant decrease in the Lenvatinib half maximal inhibitory concentration, and were more sensitive to lenvatinib-induced apoptosis (P < 0.05). In HCC subcutaneous nude mouse model, compared to the control group, the growth of tumor in APGAT4 knockdown group was significantly suppressed, and more apoptosis cells were induced (P < 0.05). Conclusion: APGAT4 promotes the growth and Lenvatinib resistance of HCC, which is a potential target for HCC treatment. Targeting APGAT4 treatment is conducive to inhibit the growth and Lenvatinib resistance of HCC.

A Novel Chinese Medicine Formula Inhibits Non-small Cell Lung Cancer by Triggering Oxidative Stress Dependent on Pentose Phosphate Pathway / 中国肺癌杂志

BACKGROUND@#Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. A novel Chinese medicine formula-01 (NCHF-01) has shown significant clinical efficacy in the treatment of NSCLC, but the mechanism of this formula in the treatment of NSCLC is not fully understood. The aim of this study is to investigate the molecular mechanism of NCHF-01 in inhibiting NSCLC.@*METHODS@#Lewis lung cells (LLC) tumor bearing mice were established to detect the tumor inhibitory effect of NCHF-01. The morphological changes of tissues and organs in LLC tumor-bearing mice were detected by hematoxylin-eosin (HE) staining. NSCLC cells were treated by NCHF-01. The effects of cell viability and proliferation were detected by MTT and crystal violet staining experiment. Flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Network pharmacology was used to predict the mechanism of its inhibitory effect of NSCLC. Western blot and immunohistochemistry (IHC) were used to detect the expression of related proteins.@*RESULTS@#NCHF-01 can inhibit tumor growth in LLC tumor-bearing mice, and has no obvious side effects on other tissues and organs. NCHF-01 could inhibit cell viability and proliferation, induce G2/M phase arrest and apoptosis, and promote the increase of ROS level. Network pharmacological analysis showed that NCHF-01 exerts anti-NSCLC effects through various biological processes such as oxidative stress and central carbon metabolism. NCHF-01 can reduce the protein expression and enzyme activity of the key enzymes 6-phosphate glucose dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) in the pentose phosphate pathway (PPP).@*CONCLUSIONS@#NCHF-01 can inhibit NSCLC through oxidative stress dependent on the PPP.

Preparation and properties of a new artificial bone composite material / 中国修复重建外科杂志

OBJECTIVE@#To study the preparation and properties of the hyaluronic acid (HA)/α-calcium sulfate hemihydrate (α-CSH)/β-tricalcium phosphate (β-TCP) material (hereinafter referred to as composite material).@*METHODS@#Firstly, the α-CSH was prepared from calcium sulfate dihydrate by hydrothermal method, and the β-TCP was prepared by wet reaction of soluble calcium salt and phosphate. Secondly, the α-CSH and β-TCP were mixed in different proportions (10∶0, 9∶1, 8∶2, 7∶3, 5∶5, and 3∶7), and then mixed with HA solutions with concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0%, respectively, at a liquid-solid ratio of 0.30 and 0.35 respectively to prepare HA/α-CSH/ β-TCP composite material. The α-CSH/β-TCP composite material prepared with α-CSH, β-TCP, and deionized water was used as the control. The composite material was analyzed by scanning electron microscope, X-ray diffraction analysis, initial/final setting time, degradation, compressive strength, dispersion, injectability, and cytotoxicity.@*RESULTS@#The HA/α-CSH/β-TCP composite material was prepared successfully. The composite material has rough surface, densely packed irregular block particles and strip particles, and microporous structures, with the pore size mainly between 5 and 15 μm. When the content of β-TCP increased, the initial/final setting time of composite material increased, the degradation rate decreased, and the compressive strength showed a trend of first increasing and then weakening; there were significant differences between the composite materials with different α-CSH/β-TCP proportion ( P<0.05). Adding HA improved the injectable property of the composite material, and it showed an increasing trend with the increase of concentration ( P<0.05), but it has no obvious effect on the setting time of composite material ( P>0.05). The cytotoxicity level of HA/α-CSH/β-TCP composite material ranged from 0 to 1, without cytotoxicity.@*CONCLUSION@#The HA/α-CSH/β-TCP composite materials have good biocompatibility. Theoretically, it can meet the clinical needs of bone defect repairing, and may be a new artificial bone material with potential clinical application prospect.

Prognostic value of serum carbamoyl phosphate synthase 1 in patients with hepatitis E-related acute liver failure / 中华检验医学杂志

Objective:To explore the impact of serum carbamoyl phosphate synthase 1 (CPS1) level on prognosis of patients with hepatitis E-related acute liver failure (HEV-ALF).Methods:This retrospective analysis included 100 HEV-ALF patients, 100 patients with acute hepatitis E (AHE) and 100 healthy controls who admitted or underwent health checkup from December 2018 to June 2019 in six hospitals, including the First Affiliated Hospital, Zhejiang University School of Medicine. HEV-ALF patients were divided into non-survial ( n=21) and survival ( n=79) subgroups according to results of 30-day follow-up results. HEV-ALF patients were also divided into the high ( n=50) and low ( n=50) serum CPS1 level groups. HEV-ALF patients were further divided into the improvement ( n=55), fluctuation ( n=32) and deterioration ( n=13) subgroups. The general clinical data from all participants were collected. Serum CPS1 levels were detected by enzyme linked immunosorbent assay. The survival time in the high and low serum CPS1 level groups were presented in the Kaplan-Meier curve. The correlation between serum CPS1 level and HEV-ALF related conventional parameters was also analyzed by linear regression. The efficacy of serum CPS1 level on predicting the 30-day mortality of HEV-ALF patients was estimated by the receiver operating characteristic curve and area under curve (AUC). Results:Serum CPS1 level was significantly higher in HEV-ALF patients than in AHE patients [958.59 (665.52, 1 105.83) pg/ml vs 549.38 (495.02, 649.08) pg/ml, P<0.001], and serum CPS1 level was significantly higher in AHE patients than in healthy controls [549.38 (495.02, 649.08) pg/ml vs 469.89 (373.32, 564.53) pg/ml, P<0.001]. The level of serum CPS1 was significantly lower in the HEV-ALF survival group than in the HEV-ALF non-survival group [922.6 (652.7, 1, 042.3) pg/ml vs 1 252.8 (933.3, 1 555.8) pg/ml, P<0.001]. In addition, the survival time was shorter in the high serum CPS1 level group than in the low serum CPS1 level group [24.59 (22.11, 27.06) d vs 28.16 (26.25, 30.07) d, P=0.045]. Serum CPS1 levels were increased in the fluctuation and deterioration groups [Fluctuation: 1 328.3 (1 184.3, 1 964.0) pg/ml vs 1 245.7 (1 102.0, 1 937.6) pg/ml, P<0.01; Deterioration: 1 483.6 (1 275.9, 1 656.8) pg/ml vs 1 332.2 (1 197.4, 1 509.8) pg/ml, P<0.01], while decreased in the improvement group [810.3 (599.7, 904.5) pg/ml vs 922.6 (679.5, 1 039.6) pg/ml, P<0.01] over time. Besides, a linear positive correlation was found between serum CPS1 level and alanine aminotransferase (ALT) and total bilirubin (TBIL) (ALT: r=0.339, P<0.001; TBIL: r=0.304, P=0.002). The AUC of serum CPS1 level to predict the 30-day mortality of HEV-ALF patients was 0.803 (95% CI 0.666-0.941), the sensitivity and specificity were 66.67% and 97.47%, respectively. Conclusion:Serum CPS1 level was significantly increased in HEV-ALF patients, and closely related to the prognosis of patients with HEV-ALF.

Role of S1PR1 in dorsal root ganglion in remifentanil-induced hyperalgesia in rats with incisional pain / 中华麻醉学杂志

Objective:To evaluate the role of sphingosine-1-phospho-1 receptor(S1PR1)in the dorsal root ganglion in remifentanil-induced hyperalgesia in rats with incisional pain.Methods:Forty-eight male Sprague-Dawley rats with successful intrathecal and caudal vein catheterization, weighing 260-280 g, aged 2-3 months, were divided into 6 groups ( n= 8 each) using a random number table method: control group (group C), S1PR1 antagonist (FTY720) group (group F), remifentanil group (group R), remifentanil + S1PR1 antagonist (FTY720) group (group R+ F), remifentanil + incisional pain group (group R+ I), and remifentanil + incisional pain + S1PR1 antagonist (FTY720) group (group R+ I+ F). In C group, normal saline 0.1 μg·kg -1·min -1 was intravenously infused for 60 min. In R group, remifentanil 1.0 μg· kg -1·min -1 was infused for 60 min through the caudal vein. In F group, FTY720 3 nmol was intrathecally injected, and 10 min later normal saline 1.0 μg· kg -1·min -1 was infused for 60 min via the caudal vein. In R+ F group, FTY720 3 nmol was intrathecally injected, and 10 min later remifentanil 1.0 μg· kg -1·min -1 was infused for 60 min through the caudal vein. In R+ I group, remifentanil 1.0 μg·kg -1·min -1 was infused for 60 min through the caudal vein while the model of incisional pain was developed. In R+ I+ F group, FTY720 3 nmol was intrathecally injected, 10 min later the incisional pain model was prepared, and remifentanil 1.0 μg·kg -1·min -1 was injected for 60 min through the caudal vein at the same time. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before remifentanil or normal saline infusion (T 0) and 2, 6, 24 and 48 h after stopping remifentanil or normal saline infusion (T 1-4). Rats were sacrificed after the last measurement of pain threshold, and the L 4-6 segments of dorsal root ganglion were taken for determination of the expression of S1PR1, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), interleukin-1β (IL-1β) and glutamate transporter-1 (GLT-1) protein and mRNA (by Western blot and quantitative polymerase chain reaction). Results:Compared with C group, the MWT was significantly decreased and TWL was shortened at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in dorsal root ganglion was up-regulated, and the expression of GLT-1 protein and mRNA in dorsal root ganglion was down-regulated in R group ( P<0.05), and no significant change was found in the parameters mentioned above in group F ( P>0.05). Compared with R group, MWT was significantly decreased and TWL was shortened at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in dorsal root ganglion was up-regulated, and GLT-1 protein and mRNA expression in dorsal root ganglion was down-regulated in R+ I group, and MWT was significantly increased and TWL was prolonged at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in the dorsal root ganglion was down-regulated, and GLT-1 protein and mRNA expression in the dorsal root ganglion was up-regulated in R+ F group ( P<0.05). Compared with R+ I group, MWT was significantly increased and TWL was prolonged at T 1-4, the expression of S1PR1, NLRP3 and IL-1β protein and mRNA in the dorsal root ganglion was down-regulated, and the expression of GLT-1 protein and mRNA in the dorsal root ganglion was up-regulated in R+ I+ F group( P<0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia is associated with up-regulation of S1PR1 expression, activation of inflammatory factors, and down-regulation of GLT-1 expression in the rats with incisional pain.

Research progress of S1P signaling pathway in eye diseases / 中华实验眼科杂志

Sphingolipid metabolism is widely involved in the functional regulation of different cells, and also plays an important role in ocular tissues.Sphingosine 1-phosphate (S1P) is the end product of sphingolipid metabolism and has been shown to play an important role in the onset and development of eye diseases.S1P signaling pathway is widely expressed in various ocular cells and is involved in the regulation of cell proliferation, differentiation, migration and apoptosis.S1P activates a variety of signaling pathways by binding to corresponding receptors and thus plays a wide range of physiological and pathological effects in the eye.Recent studies have found that the S1P signaling pathway can not only mediate the normal development of blood vessels and nerves in the eye, maintain the normal structure of the ocular tissues, and participate in the metabolism of lipids in the eye, but also has a close relationship with immune-related inflammatory response, pathological fibrosis, destruction of cell functional barrier and other related pathological changes.This paper mainly reviewed the basic overview of the S1P signaling pathway, its physiological role in the eye, and its role in the pathological changes of anterior and posterior segment diseases, so as to provide new directions and targets for the treatment of eye diseases.

Clinical analysis of severe hyperbilirubinemia caused by hemolytic disease of the newborn and G6PD deficiency / 中国新生儿科杂志

Objective:To study the clinical characteristics and differences of severe hyperbilirubinemia caused by hemolytic disease of the newborn (HDN) and glucose-6-phosphate dehydrogenase (G6PD) deficiency.Methods:From January 2014 to December 2021, newborns (gestational age ≥ 35 weeks and postnatal age ≤ 28 d) admitted to the Department of Neonatology of Hunan Children's Hospital with severe hyperbilirubinemia caused by HDN or G6PD deficiency were retrospectively analyzed. According to the etiology of hyperbilirubinemia, they were assigned into HDN group and G6PD deficiency group. The general conditions, clinical manifestations, laboratory results, treatment and prognosis of the two groups were compared using SPSS 26.0 software.Results:A total of 532 cases were in the HDN group and 413 cases in the G6PD deficiency group. The HDN group reached peak hyperbilirubinemia earlier than the G6PD deficiency group [3(2,5) d vs. 6(4,8)d, P<0.05]. The HDN group had lower peak value of total serum bilirubin [379.5(345.6,426.7) μmol/L vs. 486.4 (413.5,577.4) μmol/L] and lower incidence of anemia [37.4% (199/532) vs. 55.0% (227/413)]than the G6PD deficiency group.The incidence of anemia with elevated reticulocyte percent(Ret%) in the HDN group was higher than the G6PD deficiency group[66.3%(132/199) vs. 5.7%(13/227), P<0.05]. Compared with the G6PD deficiency group, the incidences of exchange transfusion and repeated (≥2 times) exchange transfusion, acute bilirubin encephalopathy(ABE) and the mortality rate after withdrawal of treatment in the HDN group were significantly lower ( P<0.05). Conclusions:Neonatal severe hyperbilirubinemia caused by HDN has early onset. G6PD deficiency caused hyperbilirubinemia has higher incidences of anemia, more severe jaundice and ABE, without increased Ret%.

Effects of Hydroxycamptothecin Liposomes on Myocardial Fibrosis in Heart Failure Rats by Regulating Sphingosine Kinase 1/Sphingosine-1-Phosphate Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo investigate the effects of hydroxycamptothecin liposomes （LHCPT） on myocardial fibrosis in rats with heart failure by regulating the sphingosine kinase 1 （SphK1）/sphingosine-1-phosphate （S1P） signaling pathway. MethodsSD rats were divided into control group， model group， hydroxycamptothecin （HCPT） group， LHCPT group， captopril group， and LHCPT+K6PC-5 （SphK1 activator） group， with 12 rats in each group. The heart failure rat models in all groups except the control group were established by intraperitoneal injection of doxorubicin and then the corresponding drugs were given once a day. After four weeks， we applied color Doppler ultrasound to detect left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， and left ventricular ejection fraction （LVEF） in rats； HE and Masson staining for myocardial pathological damage and myocardial fibrosis in rats， respectively； ELISA method for the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rat myocardial tissues； qRT-PCR for the expression of transforming growth factor-β1 （TGF-β1）， type I collagen （Collagen I）， and type Ⅲ collagen （Collagen Ⅲ） in rat myocardial tissues； Western blot for the expression of SphK1 and S1P proteins in rat myocardial tissues. ResultsCompared with the control group， the model group showed severe myocardial pathological damage and myocardial fibrosis， increased LVESD， LVEDD， levels of TNF-α and IL-6， expression of TGF-β1， Collagen I， Collagen Ⅲ， SphK1， S1P and decreased LVEF （P<0.05）. Compared with the model group， the HCPT group， LHCPT group and captopril group showed alleviated myocardial pathological damage and myocardial fibrosis， decreased LVESD， LVEDD， levels of TNF-α and IL-6， expression of TGF-β1， Collagen I， Collagen Ⅲ， SphK1， S1P and increased LVEF （P<0.05）. Compared with the LHCPT group， the LHCPT+K6PC-5 group showed aggravated myocardial pathological damage and myocardial fibrosis， increased LVESD， LVEDD， levels of TNF-α and IL-6， expression of TGF-β1， Collagen I， Collagen Ⅲ， SphK1， S1P and decreased LVEF （P<0.05）. ConclusionLHCPT may inhibit myocardial fibrosis in heart failure rats by inhibiting the SphK1/S1P signaling pathway.

Recent advances in poly phosphate kinase (PPK) and the construction of PPK-mediated ATP regeneration system / 生物工程学报

Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.

The S1P1 regulator IMMH002 and its therapeutic effect and mechanism on autoimmune hepatitis / 药学学报

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.