Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg^-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Humans ; Male ; Mice ; Animals ; Familial Hypophosphatemic Rickets/pathology* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/metabolism* ; Bone and Bones/metabolism* ; Phosphates/therapeutic use*

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 prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection. METHODS: DOX-loaded PELA staple fibers (F_DOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of F_DOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (G_CA4P/F_DOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of G_CA4P/F_DOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments. RESULTS: The average length of F_DOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with G_CA4P/F_DOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm³ in G_CA4P/F_DOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G_4A4P/F_DOX. CONCLUSION As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.
Animals ; Breast Neoplasms/drug therapy* ; Cell Line, Tumor ; Delayed-Action Preparations/therapeutic use* ; Doxorubicin/therapeutic use* ; Female ; Heterografts ; Humans ; Hydrogels/therapeutic use* ; Mice ; Mice, Inbred BALB C ; Phosphates

OBJECTIVE: To compare the analgesic effect of Jin Ling Zi Powder (JLZ) and its two single herbs. METHODS: The hot plate method was used to induce pain. Totally 36 mice were randomly divided into 6 groups by a complete random design, including control, model, aspirin (ASP, 0.14 g/kg body weight), JLZ (14 g/kg body weight), Corydalis yanhusuo (YHS, 14 g/kg body weight), and Toosendan Fructus (TF, 14 g/kg body weight) groups, 6 mice in each group. The mice in the control and model groups were given the same volume of saline, daily for 2 consecutive weeks. At 30, 60, 90, and 120 min after the last administration, the pain threshold of mice in each group was measured, and the improvement rate of pain threshold was calculated. Serum endogenous metabolites were analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS: There was no statistical difference in pain threshold among groups before administration (P>0.05). After 2 weeks of administration, compared with the model group, the pain threshold in JLZ, YHS, TF and ASP groups were increased to varying degrees (P<0.05). JLZ had the best analgesic effect and was superior to YHS and TF groups. A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs. These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis and inositol phosphate metabolism. CONCLUSIONS The analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor, producing post-synaptic potential, reducing the excitability of neurons, and weakening the afferent effect of painful information.
Animals ; Mice ; Analgesics/therapeutic use* ; Aspirin/pharmacology* ; Biomarkers ; Body Weight ; Drugs, Chinese Herbal/therapeutic use* ; Glycine ; Glyoxylates ; Inositol Phosphates ; Isoleucine ; Leucine ; Metabolomics/methods* ; Powders ; RNA, Transfer ; Serine ; Threonine ; Valine

PURPOSETo develop a novel injectable strontium-containing calcium phosphate cement with collagen.

METHODSA novel calcium phosphate bone cement (CPC) was prepared with the addition of strontium element, collagenl, and modified starch; the injectability, solidification time, microstructure, phase composition, compressive strength, anti-collapsibility and histological properties of material were evaluated.

RESULTSThe results showed that the material could be injected with an excellent performance; the modified starch significantly improved the anti-washout property of cement; with the liquid to solid ratio of 0.3, the largest compressive strength of cement was obtained (48.0 MPa ± 2.3 MPa); histological examination of repair tissue showed that the bone was repaired after 16 weeks; the degradation of cement was consistent with the new bone growth.

CONCLUSIONA novel injectable collagen-strontium-containing CPC with excellent compressive strength and suitable setting time was prepared, with addition of modified starch. The CPC showed a good anti-washout property and the degradation time of the cement met with the new bone growing. This material is supposed to be used in orthopedic and maxillofacial surgery for bone defects.

Animals ; Bone Cements ; chemistry ; therapeutic use ; Calcium Phosphates ; chemistry ; Collagen ; chemistry ; Compressive Strength ; Histocompatibility Testing ; Injections ; Rabbits ; Strontium ; chemistry

BACKGROUND/AIMS: Performance of polyethylene glycol solution (PEG) is often unsatisfactory as bowel preparation agent for colonoscopy. In order to provide equivalent efficacy with better patient tolerance, sodium phosphate tablet (SPT) has been developed. This study was carried out to compare the efficacy and compliance of two bowel preparation methods: PEG with ascorbic acid (PEGA) vs. SPT preparation. METHODS: A multicenter, randomized controlled trial was performed. Primary efficacy variable was overall quality of colon cleansing assessed by Boston bowel preparation scale (BBPS) during colonoscopy. Patient's satisfaction and adverse events were evaluated by means of symptom questionnaire completed by each patient immediately before colonoscopy. RESULTS: A total of 189 patients were randomly assigned to undergo pre-colonoscopic bowel preparation with either SPT (n=96) or PEGA (n=93). Overall BBPS score was 8.3+/-1.12 in the SPT group and 8.4+/-0.96 in the PEGA group (p=0.441). Among the 189 patients, 90 had polyps (47.6%) and 50 had adenomas (26.5%). The polyp/adenoma detection rate was 54.2% (n=52)/27.1% (n=26) for SPT group and 40.9% (n=38)/25.8% (n=24) for PEGA group (p=0.079 and 0.790, respectively). More number of patients were unable to take the prescribed dose of PEGA compared with the SPT regimen (8.6% vs. 2.0%, p=0.045). Overall satisfaction score was 7.9+/-1.63 in the SPT group and 7.4+/-1.53 in the PEGA group (p=0.022). CONCLUSIONS: Degree of colon preparation, polyp/adenoma detection rate and adverse effect were similar between SPT group and PEGA group. Patient compliance and satisfaction were greater in the SPT group.
Abdominal Pain/etiology ; Adenoma/pathology ; Adult ; Ascorbic Acid/*therapeutic use ; Cathartics/adverse effects/*therapeutic use ; Colonic Polyps/pathology ; *Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Nausea/etiology ; Patient Satisfaction ; Phosphates/*therapeutic use ; Polyethylene Glycols/*therapeutic use ; Surveys and Questionnaires

The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group (n=28) and control group (n=26). The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC scores at third month after treatments were compared between the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen (BUN), serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, total cholesterol between case group and control group (P>0.05 for all). There was also no significant difference in the baseline itching scores between the case group and the control group (P>0.05). At 1st and 3rd month after treatment, the itching scores in the case group were 14.2 ± 3.2 and 10.5 ± 2.3, respectively, which were significantly lower than the baseline and those in the control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching scores in the control group were 23.6 ± 5.9 and 24.8 ± 6.3, respectively, which were significantly higher than the baseline (P<0.05). There was no significant difference in the baseline of serum calcium, phosphorus, calcium-phosphorus products, iPTH levels between the case group and control group (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group (P<0.05). The AAC scores showed statistically significant difference between the case group and the control group (P<0.05). The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phosphorus and iPTH levels, resulting in the attenuation of vascular calcification.
Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Lanthanum ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Parathyroid Hormone ; analysis ; Phosphates ; blood ; Pruritus ; blood ; drug therapy ; etiology ; Renal Dialysis ; adverse effects ; methods ; Treatment Outcome ; Vascular Calcification ; blood ; drug therapy

OBJECTIVE: To evaluate the osteogenetic character and repairing maxillary sinus superior wall fractures capability of calcium phosphate cement (CPC) before and after combined with recombinant human bone morphogenetie protein-7(rhBMP-7). METHOD: A 10 mmX5 mm bone defect in the maxillary sinus superior wall was induced by surgery in all 24 New Zealand white rabbits. These 24 rabbits were randomly divided into two groups. The defects were repaired with CPC group (n = 12) and CPC/rhBMP-7 group (n = 12). The osteogenesis of bone defect was monitored by gro'ss observation, histological examination, observation under scanning electron microscope and measurement of ALP activity at 6 and 12 weeks after the implantation. RESULT: In group CPC,new bone was found to form slowly and little by little. In group CPC/rhBMP-7, however, new bone was observed to form early and massively. The ALP activity in group CPC showed significant statistical difference with that of group CPC/rhBMP-7 (P < 0.05). CONCLUSION The CPC/rhBMP-7 composite has osteoconductibility and osteoinductibility, comparing the use of CPC/rhBMP-7 with CPC for the repair of orbital fracture, the former show obvious advantage repairing ability in maxillary sinus superior wall defect.
Animals ; Bone Cements ; chemistry ; therapeutic use ; Bone Morphogenetic Protein 7 ; therapeutic use ; Calcium Phosphates ; chemistry ; Disease Models, Animal ; Fractures, Bone ; pathology ; surgery ; Humans ; Maxillary Sinus ; pathology ; Osteogenesis ; Rabbits ; Random Allocation ; Recombinant Proteins ; therapeutic use

PURPOSE: Bowel cleansing is generally regarded as time-consuming and unpleasant among patients. Patients commonly state that bowel preparation provokes more discomfort than the actual colonoscopic examination. The purpose of this study was to compare two regimens of sodium phosphate (NaP) tablets versus polyethylene glycol (PEG) solution for bowel preparation in healthy Korean adults. MATERIALS AND METHODS: This was a single center, prospective, open-label, investigator-blinded, randomized, controlled-pilot study. A total of 62 healthy Korean subjects were randomly assigned to two groups (NaP vs. PEG). Efficacy, safety, and patient-related outcomes, as well as procedural parameters, were evaluated. RESULTS: Although there were no significant differences in total Ottawa bowel quality score, fluid scores and the rate of adequate bowel preparation were significantly better in the NaP group than the PEG group. Additionally, the NaP group showed better results regarding patient tolerance, satisfaction, preference, and rate of adverse events than the PEG group. Significant fluctuations in specific serum electrolytes were common and of a greater magnitude in the NaP group than the PEG group. However, these abnormalities were transient and did not result in serious complications and side effects. CONCLUSION: In this study, NaP tablets were shown to be an effective, well-tolerated, and acceptable regimen for bowel preparation. Also, our study suggests that NaP tablets may be safe and can be used as a bowel cleansing agent in healthy adults undergoing elective colonoscopy. Further multicenter, large scale studies are needed to confirm these findings.
Adult ; Asian Continental Ancestry Group ; *Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Phosphates/*administration & dosage/therapeutic use ; Pilot Projects ; Polyethylene Glycols/*administration & dosage/therapeutic use ; Prospective Studies ; Republic of Korea ; Surface-Active Agents/*administration & dosage ; Tablets ; Therapeutic Irrigation/*methods

OBJECTIVETo assess the clinical outcomes of balloon kyphoplasty assisted with calcium phosphate cement (CPC) in treating osteoporotic vertebral fractures (OVF).

METHODSFrom January 2009 to January 2011, 26 patients with osteoporotic vertebral fractures were treated with balloon kyphoplasty assisted with CPC, including 31 vertebrae. There were 15 males and 11 females with an average age of (71.67 +/- 4.36) years old (ranged from 60 to 89 years). Course of disease was from 0.5 to 7 days with an average of 3.2 days. Clinical outcomes were assessed by the visual analogue scale (VAS) and the oswestry disability index (ODI). Vertebral height loss and kyphotic angle were measured by X-rays.

RESULTSAll patients were followed up for 10 to 24 months with an average of 18 months. Before operation, 24 hours after operation and at final follow-up, VAS scores were 7.91 +/- 1.20, 3.22 +/- 1.12, 1.92 +/- 0.83, respectively; ODI scores were 40.00 +/- 1.15, 17.00 +/- 2.12, 13.00 +/- 1.42, respectivesly; vertebral heights were (18.21 +/- 3.21), (23.82 +/- 3.10), (21.85 +/- 3.24) mm, respectivesly; vertebral kyphosis angles were (18.21 +/- 3.21) degrees, (7.42 +/- 3.13) degrees, (10.01 +/- 3.11) degrees, respectivesly. There was significant difference between preoperation and 24 hours after operation, and between final follow-up and preoperation (P < 0.05). There was no significant difference between final follow-up and 24 hours after operation (P > 0.05).

CONCLUSIONBalloon kyphoplasty assisted with calcium phosphate cement (CPC) is effective for the treatment of osteoporotic vertebral fractures (OVF), which can expeditiously relieve pain and effectively rebuild height of vertebral body and kyphotic angle, and also has advantages of minimal trauma and good security.

Aged ; Aged, 80 and over ; Bone Cements ; Calcium Phosphates ; therapeutic use ; Female ; Humans ; Kyphoplasty ; methods ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Spinal Fractures ; surgery ; Visual Analog Scale