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.
Calcium Phosphates ; Bone and Bones ; Phosphates

Background: Myo-inositol has emerged as one of the preventive therapies for the development of gestational diabetes mellitus in at-risk populations. This systematic review and meta-analysis was conducted to determine the efficacy and safety of myo-inositol in decreasing the incidence of gestational diabetes in overweight and obese pregnant women. Methodology: This meta-analysis was conducted using the standard Cochrane methodology and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. Inclusion criteria were randomized controlled trials (RCTs) that enrolled overweight and obese pregnant women and used myo-inositol supplementation. The primary outcome was the incidence of gestational diabetes mellitus at 24-28 weeks. Secondary outcomes included cesarean section rate, the incidence of pregnancy-induced hypertension, macrosomia and preterm delivery. Risk ratios (RRs) and 95% confidence intervals (CIs) were used for dichotomous data. Results: Six RCTs were included. Compared to standard micronutrient supplementation, standard dose of myo-inositol (4 g) may reduce the incidence of GDM (RR 0.54; CI [0.30, 0.96]; n = 887 women), but the certainty of evidence is low to very low. With low-dose myo-inositol however, evidence is uncertain about its benefit on the incidence of gestational diabetes mellitus in overweight and obese women with RR 0.71; CI [0.14, 3.50]. No adverse effects were noted. For the secondary outcomes, standard dose myo-inositol appears to reduce the incidence of pregnancy-induced hypertension and preterm delivery, but the certainty of evidence is low to very low. Conclusion Current evidence is uncertain on the potential benefit of myo-inositol supplementation in overweight and obese pregnant women. While studies show that 4 g myo-inositol per day may decrease the incidence of GDM, pregnancy-induced hypertension and pre-term birth with no associated risk of serious adverse events, the certainty of evidence is low to very low. Future high-quality trials may provide more compelling evidence to support practice recommendations.
Diabetes, Gestational ; Obesity ; Inositol Phosphates

PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Humans ; Cell Membrane ; Mutation, Missense ; Phosphates/metabolism* ; Sodium-Phosphate Cotransporter Proteins, Type III/genetics*

OBJECTIVE: To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism. METHODS: A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. RESULTS: Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group. CONCLUSIONS PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Sepsis-Associated Encephalopathy ; Phosphates ; Actins ; Beclin-1 ; Interleukin-6 ; Autophagy ; Ubiquitin-Protein Ligases ; Cognitive Dysfunction ; Sepsis ; Mitochondria ; Protein Kinases

Water eutrophication poses great threats to protection of water environment. Microbial remediation of water eutrophication has shown high efficiency, low consumption and no secondary pollution, thus becoming an important approach for ecological remediation. In recent years, researches on denitrifying phosphate accumulating organisms and their application in wastewater treatment processes have received increasing attention. Different from the traditional nitrogen and phosphorus removal process conducted by denitrifying bacteria and phosphate accumulating organisms, the denitrifying phosphate accumulating organisms can simultaneously remove nitrogen and phosphorus under alternated anaerobic and anoxic/aerobic conditions. It is worth noting that microorganisms capable of simultaneously removing nitrogen and phosphorus absolutely under aerobic conditions have been reported in recent years, but the mechanisms remain unclear. This review summarizes the species and characteristics of denitrifying phosphate accumulating organisms and the microorganisms capable of performing simultaneous nitrification-denitrification and phosphorous removal. Moreover, this review analyzes the relationship between nitrogen removal and phosphorus removal and the underlying mechanisms, discusses the challenges of denitrifying phosphorus removal, and prospects future research directions, with the aim to facilitate process improvement of denitrifying phosphate accumulating organisms.
Phosphorus ; Phosphates ; Wastewater ; Denitrification ; Waste Disposal, Fluid ; Nitrogen ; Bioreactors/microbiology* ; Nitrification ; Sewage

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.
Adenosine Triphosphate/metabolism* ; Adenosine Monophosphate ; Polyphosphates/metabolism* ; Catalysis ; Regeneration

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.
Humans ; Antipyretics/therapeutic use* ; Antiviral Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Influenza, Human/drug therapy* ; Nucleic Acids/therapeutic use* ; Oseltamivir/therapeutic use* ; Phosphates/therapeutic use* ; Treatment Outcome ; Double-Blind Method

OBJECTIVE: To investigate the preparation and properties of the novel silica (SiO ₂)/hydroxyapatite (HAP) whiskers porous ceramics scaffold. METHODS: The HAP whiskers were modified by the SiO ₂ microspheres using the Stöber method. Three types of SiO ₂/HAP whiskers were fabricated under different factors (for the No.1 samples, the content of tetraethoxysilane, stirring time, calcination temperature, and soaking time were 10 mL, 12 hours, 560℃, and 0.5 hours, respectively; and in the No.2 samples, those were 15 mL, 24 hours, 650℃, and 2 hours, respectively; while those in the No.3 samples were 20 mL, 48 hours, 750℃, and 4 hours, respectively). The phase and morphology of the self-made HAP whisker and 3 types of SiO ₂/HAP whiskers were detected by the X-ray diffraction analysis and scanning electron microscopy. Taken the self-made HAP whisker and 3 types of SiO ₂/HAP whiskers as raw materials, various porous ceramic materials were prepared using the mechanical foaming method combined with extrusion molding method, and the low-temperature heat treatment. The pore structure of porous ceramics was observed by scanning electron microscopy. Its porosity and pore size distribution were measured. And further the axial compressive strength was measured, and the biodegradability was detected by simulated body fluid. Cell counting kit 8 method was used to conduct cytotoxicity experiments on the extract of porous ceramics. RESULTS: The SiO ₂ microspheres modified HAP whiskers and its porous ceramic materials were prepared successfully, respectively. In the SiO ₂/HAP whiskers, the amorphous SiO ₂ microspheres with a diameter of 200 nm, uniform distribution and good adhesion were attached to the surface of the whiskers, and the number of microspheres was controllable. The apparent porosity of the porous ceramic scaffold was about 78%, and its pore structure was composed of neatly arranged longitudinal through-holes and a large number of micro/nano through-holes. Compared with HAP whisker porous ceramic, the axial compressive strength of the SiO ₂/HAP whisker porous ceramics could reach 1.0 MPa, which increased the strength by nearly 4 times. Among them, the axial compressive strength of the No.2 SiO ₂/HAP whisker porous ceramic was the highest. The SiO ₂ microspheres attached to the surface of the whiskers could provide sites for the deposition of apatite. With the content of SiO ₂ microspheres increased, the deposition rate of apatite accelerated. The cytotoxicity level of the prepared porous ceramics ranged from 0 to 1, without cytotoxicity. CONCLUSION SiO ₂/HAP whisker porous ceramics have good biological activity, high porosity, three-dimensional complex pore structure, good axial compressive strength, and no cytotoxicity, which make it a promising scaffold material for bone tissue engineering.
Animals ; Durapatite ; Porosity ; Vibrissae ; Apatites ; Ceramics ; Silicon Dioxide

OBJECTIVES: To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. METHODS: A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. RESULTS: There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). CONCLUSIONS The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.
Child ; Humans ; Human Growth Hormone/pharmacology* ; Insulin-Like Growth Factor I/pharmacology* ; Fibroblast Growth Factor-23 ; Prospective Studies ; Growth Disorders ; Phosphates/pharmacology* ; Body Height

The composite material PLGA compounded with β-tricalcium phosphate (β-TCP) was prepared by melt blending method, and the absorbable interface screw was prepared by injection molding process. Prepare PBS buffer that simulates human body, conduct in vitro degradation experiments on interface screws according to relevant national and industry standards, then test and characterize interface screws at different time points for degradation of intrinsic viscosity, average molecular weight distribution, mass loss, mechanical properties and thermal properties. According to the degradation performance-time curve, determine the time node at which the interface screw loses the mechanical properties. In this paper, the in vitro degradation behavior of interfacial screws prepared from PLGA and β-TCP composites was studied in detail, providing a reference and basis for the degradation behavior of absorbable products prepared from PLGA and β-TCP composites.
Humans ; Polyesters ; Materials Testing ; Calcium Phosphates ; Absorbable Implants