[Histone acetylation in the development and regeneration of craniofacial hard tissue].

Craniofacial hard tissue mainly includes craniofacial bone and tooth, which is one of the important parts of the mouth-jaw system. Congenital aplasia, tumors and trauma can cause large craniofacial hard tissue defects, which are detrimental to the facial appearance and function of patients, and affect the physical and mental health of patients. Histone acetylation modification is the earliest and most widely studied histone modification, which is an epigenetic modification mechanism jointly regulated by histone acetyltransferase and histone deacetylase. In this paper, we will review the research progress of histone acetylation mediated by histone acetyltransferase and histone deacetylase in the development and regeneration of craniofacial hard tissue.

[Analysis of the progress in the field of oral microbiology and regenerative medicine from 2014 to 2023].

Objective: To analyze the trends in literature related to oral microbiology and regenerative medicine from 2014 to 2023. By identifying key research countries, institutions, and their collaboration networks, as well as exploring research hotspots and development directions, the study seeks to provide references for researchers and decision-makers in the field of oral microbiology and regenerative medicine, thereby guiding the direction of future research. Methods: Relevant literature was retrieved using the Web of Science Core Collection database, with data processing and analysis conducted using CiteSpace 6.2.R6 software. Time slicing, node type selection, and the application of the g-index (g-index) were used for filtering, analyzing countries, institutions, authors, journals, and keywords. Results: The volume of literature in the field of oral microbiology and regenerative medicine has steadily increased from 2014 to 2023, with the number of publications first exceeding one hundred in 2020 and reaching 134 in 2022, accompanied by a citation frequency of 3 363 times. China and the United States have been at the forefront in terms of the volume of publications, while the United States and Germany lead in terms of intermediary centrality. The research primarily spans disciplines such as oral medicine, interdisciplinary studies, materials science, and immunology. High-frequency keywords include stem cells, scaffold materials, and gut microbiota, while cluster analysis indicates that inflammation, drug delivery, and antimicrobial activity remain consistent research themes. In recent years, the research heat in "tissue regeneration""gut microbiota " and "maxillofacial surgery" has risen, suggesting these may become focal points of future research. Conclusions: Over the past decade, the volume of literature published in the fields of oral microbiology and regenerative medicine, along with their citation frequencies, has increased annually. The research focus has shifted over time. Understanding the interactions between oral and gut microbiomes is crucial for developing innovative regenerative treatment strategies.

[Clinical features and prognostic factors of severe hemophagocytic syndrome in children].

Objective: To explore the clinical characteristics, prognostic risk factors and effective treatment of severe hemophagocytic syndrome (HPS) in children, so as to provide reference for the clinical diagnosis and treatment of the disease. Methods: The clinical data of 83 children with severe HPS admitted in Affiliated Hospital of Zunyi Medical University from January 2014 to April 2021 were collected, and their clinical characteristics, prognosis and prognostic risk factors were analyzed. The children were divided into central nervous system (CNS) dysfunction group and non-CNS dysfunction group according to whether they were accompanied with CNS dysfunction, and were divided into blood purification group and non-blood purification group according to whether they received blood purification, then the survival differences were compared. Results: Among the 83 children, there were 43 males and 40 females, aged[M(Q1,Q3)] 36(15,27)months. A total of 51 children were induced by infection, among which 41 children (80.4%) were infected with EB virus. All the children were accompanied by multiple organ dysfunction (MODS), and dysfunction of the blood system (72.3%), liver (71.1%), respiratory system (53.0%) and CNS (37.3%) were common. By the end of follow-up, 40 cases (48.2%) survived, 38 cases (45.8%) died, and 5 cases (6.0%) were lost to follow-up. CNS dysfunction was a risk factor (HR=3.358, 95%CI: 1.445-7.803, P=0.005) and blood purification was a protective factor (HR=0.362, 95%CI: 0.179-0.730, P=0.005) affecting the prognosis of children. The mortality of CNS dysfunction group was statistically higher than that of non-CNS dysfunction group (74.2% vs 28.8%) (P<0.001); The mortality of blood purification group was statistically lower than that of non-blood purification group (31.0% vs 61.0%) (P=0.010). Conclusions: Severe HPS in children was dangerous and had a poor overall prognosis. CNS dysfunction was a risk factor for death. Blood purification could significantly improve the prognosis and improve the survival rate of children.

[Microcontact printing and its application prospect in bone tissue engineering].

The application of bone tissue engineering regeneration technology is expected to repair maxillofacial bone tissue defects caused by tumors, trauma, etc. Surface patterning occupies an important position in bone tissue engineering. Microcontact printing is an emerging technology through which the elastic stamp contacts with the substance and materials used as ink can be transferred from stamp to substance to form patterns. The biggest characteristic of the technology is to fabricate high-throughput and high-accuracy patterned surface, making it widely applied. This review summarized the application and optimization of microcontact printing, and prospected its application in bone tissue engineering.

International normalised ratio as an independent predictor of mortality in limb necrotising fasciitis with sepsis.

INTRODUCTION: Necrotising fasciitis with sepsis is a life threatening disease. The aim of this study was to analyse the association between international normalised ratio (INR) and mortality in sepsis patients with necrotising fasciitis. METHODS: A retrospective review was undertaken of 106 patients suffering from necrotising fasciitis with sepsis between November 2007 and December 2016. Data on comorbidities, clinical manifestations, laboratory findings, causative microbiological organisms, APACHE II (Acute Physiology and Chronic Health Evaluation II) score and outcomes were extracted. Logistic regression was carried out to examine the factors affecting mortality. RESULTS: Forty patients (37.7%) died. There was no significant difference in the white blood count (WBC) for the survivor and non-survivor groups. Non-survivors had a lower mean oxygenation index (OI) (288.7mmHg vs 329.4mmHg, p=0.032) and platelet count (PC) (139.5 vs 214.8 x 109/l, p=0.028), and a higher mean INR (1.9 vs 1.3, p=0.000), activated partial thromboplastin time (APTT) (54.6 vs 44.2 seconds, p=0.005) and serum creatinine (2.3mg/dl vs 1.4mg/dl, p=0.007). Mortality in patients with INR >1.5 was significantly higher than in those with INR <1.5 when all risk factors (WBC, PC, OI, INR, APTT, creatinine) were considered (odds ratio: 4.414, 95% confidence interval: 1.263-15.428, p=0.020). Even after adjusting for age, sex, bacteraemia, diabetes and hepatic disorders, the data still exhibited elevated mortality for patients with INR >1.5 (odds ratio: 5.600, 95% confidence interval: 1.415-22.166, p=0.014). CONCLUSIONS: INR is a significant independent predictor of mortality in sepsis patients diagnosed with necrotising fasciitis.

Irisin alleviates renal injury caused by sepsis via the NF-κB signaling pathway.

OBJECTIVE: Renal injury caused by sepsis is a difficult point in the field of critical care medicine today, which seriously endangers the health of patients. The aim of our paper was to study the role of irisin in the inflammation and apoptosis of renal injury caused by sepsis and its potential mechanism of action. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was utilized to establish an acute kidney injury model. HK-2 cells were divided into 3 groups: control group, LPS group, LPS+irisin group. The expression of TNF-α, IL-1ß, Bcl-2, and Bax were detected using Western blot. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of TNF-α, IL-6, and IL-1ß in the cell supernatant. The LDH content was detected to observe cell damage. TUNEL staining and flow cytometry were to investigate the apoptosis in three groups. The viability of HK-2 cells was detected using Cell Counting Kit-8 (CCK-8) assay. RESULTS: After HK-2 cells were treated with LPS, the LDH content in the cell supernatant was greatly increased, and the expression of TNF-α, IL-6, and IL-1ß was also significantly increased. However, after treatment with irisin, LDH content and expression of inflammatory factors were significantly suppressed. Similarly, LPS treatment greatly elevated the levels of TNF-α, IL-1ß, Bax, p65 and IκKα, as well as inhibited the expression of Bcl-2 and IκB-α. However, irisin treatment reversed these situations. In addition, the number of TUNEL-positive cells and the apoptotic rate were also greatly decreased in LPS+irisin group compared with those in LPS group. CONCLUSIONS: Irisin could inhibit inflammation and apoptosis of HK-2 cells treated with LPS via the NF-κB pathway.

The Function of Wnt Ligands on Osteocyte and Bone Remodeling.

Bone homeostasis is continually maintained by the process of bone remodeling throughout life. Recent studies have demonstrated that Wnt signaling pathways play a fundamental role in the process of bone homeostasis and remodeling. Intracellular Wnt signaling cascades are initially triggered by a Wnt ligand-receptor complex formation. In previous studies, the blocking of Wnt ligands from different osteoblastic differentiation stages could cause defective bone development at an early stage. Osteocytes, the most abundant and long-lived type of bone cell, are a crucial orchestrator of bone remodeling. However, the role of Wnt ligands on osteocyte and bone remodeling remains unclear. In our present study, we found that, besides osteoblasts, osteocytes also express multiple Wnt ligands in the bone environment. Then, we used a Dmp1-Cre mouse line, in which there is expression in a subset of osteoblasts but mainly osteocytes, to study the function of Wnt ligands on osteocyte and bone remodeling in vivo. Furthermore, we explored the role of Wnt ligands on osteocytic mineralization ability, as well as the regulatory function of osteocytes on the process of osteoblastic differentiation and osteoclastic migration and maturity in vitro. We concluded that Wnt proteins play an important regulatory role in 1) the process of perilacunar/canalicular remodeling, as mediated by osteocytes, and 2) the balance of osteogenesis and bone resorption at the bone surface, as mediated by osteoblasts and osteoclasts, at least partly through the canonical Wnt/ß-catenin signaling pathway and the OPG/RANKL signaling pathway.

Effect of dexmedetomidine on kidney injury in sepsis rats through TLR4/MyD88/NF-κB/iNOS signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of dexmedetomidine (DEX) on kidney injury in sepsis rats through the Toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88)/nuclear factor-κB (NF-κB)/inducible nitric oxide synthase (iNOS) signaling pathway. MATERIALS AND METHODS: A total of 30 Sprague-Dawley (SD) rats were randomly divided into three groups, including the control group (n=10), lipopolysaccharide (LPS)-induced acute kidney injury (AKI) group (model group, n=10) and DEX treatment group (DEX group, n=10). The model of sepsis was successfully established in rats. The levels of serum creatinine (Cr), blood urea nitrogen (BUN), serum interleukin-6 (IL-6), IL-1ß, IL-10 and tumor necrosis factor-α (TNF-α) were detected via enzyme-linked immunosorbent assay (ELISA). The pathological changes in kidney tissues were detected via hematoxylin-eosin (HE) staining. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS in the kidney were detected via fluorescence quantitative Polymerase Chain Reaction (PCR) and Western blotting, respectively. RESULTS: Compared with the control group, rats in the model group showed significant kidney injury, markedly increased levels of serum Cr, BUN and pro-inflammatory cytokines, remarkably decreased the level of IL-10 (p<0.05), and significantly increased mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS. In the DEX group, AKI was markedly improved, while the expressions of inflammatory cytokines were remarkably declined. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS decreased significantly. CONCLUSIONS: DEX has a protective effect on LPS-induced AKI, whose mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB/iNOS pathway.

[Application of negative molds technology based on three-dimensional printing in digital maxillofacial prostheses].

Objective: To explore a digital negative molds technique based on three-dimensional (3D) printing to assist in the manufacture of maxillofacial prostheses, and to improve the deficiency of the current clinical treatment. Methods: Seventeen patients with maxillofacial defects (including nasal defects, orbital defects, cheek defects, auricle defect) were scanned by means of facial optical scanning and computer tomography (CT). The 3D models were then reconstructed and global registration was made to merge the reconstructed models into a new digital model for 3D design. The 3D design of the prostheses was implemented in software. The mechanical connection structure was designed by forward engineering technology for 3 patients with intra-oral defects in maxilla who needed to make removable partial dentures, so that the silicone prostheses and removable partial denture could be combined. The removable partial dentures were made by conventional method and connected with the prostheses. According to the 3D data of the prostheses, the digital negative molds were designed, and the 3D printing technology was used to finish the processing of the resin molds. Silicone for prostheses were filled and cured in the resin molds to fabricate the clinical restorations for the patients. The margin adaptation and retention of the prostheses was detected. Results: Twenty patients with varying degrees of maxillofacial defects were rehabilitated using the courses developed in the study. All patients reported no pain or discomfort during the treatment; and they were satisfied with the final prostheses of the shape, color, retention, stability, etc. Eighteen of the prostheses showed good marginal adaptation, and sixteen of the prostheses showed good retention effect. Conclusions: The digital negative molds technique used in this study could greatly reduce the intensity of manual operation and provided a good therapeutic effect for patients with maxillofacial defects.

[Hand, foot and mouth disease in Hubei province, 2009-2015: an epidemiological and etiological study].

Objective: To clarify the age patterns and types of differences so as to provide reference on prevention and interventions of hand, foot and mouth disease (HFMD) cases, in Hubei province. Methods: We collected the HFMD case information of Hubei province from the Chinese National Notifiable Infectious Disease Reporting System in 2009-2015 while the information on pathogens from the laboratory monitoring system of Center for Disease Control and Prevention at all levels in Hubei province. All the data were stratified by age, disease severity, laboratory confirmation status, and serotypes of enterovirus. Results: There were 495 783 reported HFMD cases from 2009 to 2015, in Hubei province, of which 1 045 were severe with 99 fatal. The annual notification rate was 1 231.0/10(6). HFMD cases were concentrated mainly in 0.5-5 year olds, with highest severity and mortality seen in 6-11 month-olds. The predominated pathogen in mild laboratory-confirmed cases each year, in order during 2009-2015 as: EV71, Cox A16, Cox A16, Cox A16, EV71, Cox A16 and other EV. HFMD showed semiannual peaks in April-June, November-December, and with more cases in the even years than in the odd years. Conclusions: Children aged 0.5 to 5 years with 6 to 11 month-olds in particular, were the focused groups of attention in Hubei province. Our findings provided evidence for the improvement on monitoring program. Targeted intervention approaches should be strengthened to reduce the mortality and morbidity of HFMD in the province.

[Correlation with MRI features, cell density and the expression of immunohistochemistry of pure mucinous breast carcinoma].

Objective: To explore the MRI features of the pure mucinous breast carcinoma(PMBC) and the correlation with cell density and the expression of immunohistochemistry. Methods: MRI features of 35 pure mucinous carcinomas were retrospectively analyzed from January 2011 to May 2016 in Guangdong General Hospital. MR images were reviewed for shape, margin, the signal intensity, enhancement patterns of tumors and diffusion weighted imaging (DWI) features and apparent diffusion coefficient (ADC) value. All the patients were detected by immunohistochemical staining with expression of ER, PR, CerbB-2, Ki-67 and Her-2. Correlations between MRI features of PMBC and cell density and the expression of immunohistochemistry were analyzed. Results: A total of 16 oval masses(16/35, 45.7%) and 10 round masses(10/35, 28.6%)were found in 35 PMBC with clear boundary(26/35, 74.3%) and lobulated shape(31/35, 88.6%). Very high signal intensity on T(2)-weighted images was found in 33 PMBC (33/35, 94.3%) and early enhancement rate was 115%±9% for PMBC. 28 PMBC demonstrated persistent enhancing pattern on time-signal intensity curve and 7 PMBC demonstrated plateau pattern.Mean ADC value was (1.91±0.06)×10(-3)mm(2)/s for PMBC. There was significant difference with early enhancement rate and ADC value between PMBC with more or less quantities of cellular mucin (P<0.05). There was no significant difference with ER, PR, CerbB-2, Her-2 and Ki-67 expression between PMBC with more or less quantities of cellular mucin (all P>0.05). Conclusions: PMBC has distinctive MRI features. The prognosis of PMBC is better from correlation between MRI features, cell density and the expression of immunohistochemistry.

[Biomaterials for bone defect repair and bone regeneration].

The treatment of large jaw bone defects remains an urgent clinical problem to be solved. With the development of biomaterials, stem cells and bone tissue engineering, new ideas and hopes for the regeneration of jaw have been offered. In addition to meeting the basic requirements of bone repair materials, scaffolds for the regeneration of large jaw bones require the ability of stem cells to participate in bone regeneration. Methods like optimization of scaffolds composition, design of porous structure and combination of gel and microsphere technology can enhance stem cell delivery in vivo, and the osteogenic differentiation of stem cells can be stimulated through controlled release of drugs, preparation of surface micron/nano topography and modifications of ionic components. Moreover, application of three-dimensional printing and channel structure in large-scale scaffolds fabrication present promising strategies for customized, accurate bone reconstruction and vascularization. It is only through synergistic optimization in all aspects that it is possible to obtain scaffold materials suitable for regeneration of large jaw bones. This article focuses on biological materials regulation, stem cell delivery, survival and differentiation, and their role in bone regeneration.

Association of the programmed cell death-1 PD1.5 C>T polymorphism with cervical cancer risk in a Chinese population.

The association of the programmed cell death-1 PD1.5 C>T polymorphism with cervical cancer risk has not been investigated. In this hospital-based case-control study, we analyzed 256 patients with cervical cancer and 250 healthy controls. Pearson chi-square test was used to examine differences in the distribution of genotypes between cases and controls. Association between the polymorphism and the susceptibility to cervical cancer was evaluated using unconditional logistic regression analysis. This revealed that the frequencies of the three genotypes (CC, CT, and TT) in cervical cancer cases and controls were 17.58, 65.23, and 17.19% and 24.80, 40.40, and 34.80%, respectively; the difference between the two groups was significant (P < 0.001). We found that the CT genotype was significantly associated with increased cervical cancer risk (adjusted OR = 2.18; 95%CI = 1.37-6.11; P = 0.009). Moreover, there was significant association between PD-1.5 C/T polymorphism and susceptibility to cervical cancer under dominant model (OR = 1.27, 95%CI = 1.01-2.15, P = 0.047). We conclude that the PD-1.5 C/T polymorphism may be associated with increased risk of cervical cancer. The study also highlights the importance of conducting genetic association studies in different ethnic populations.

Altered corticostriatal functional connectivity in individuals with high social anhedonia.

BACKGROUND: Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia. METHOD: Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17-21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect. RESULTS: Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression. CONCLUSIONS: Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.

Effects of TiO2 nanotube layers on RAW 264.7 macrophage behaviour and bone morphogenetic protein-2 expression.

OBJECTIVES: To investigate behaviour and osteogenic cytokine expression of RAW264.7 macrophages grown on TiO2 nanotube layers. MATERIALS AND METHODS: The murine macrophage cell line RAW 264.7 was cultured on TiO2 nanotubes of varying diameter; macrophage morphology was examined using scanning electron microscopy. Cell adhesion and viability were assessed with the aid of the MTT method and BMP-2 and TGF-ß gene expression were examined by RT-PCR analysis. Levels of BMP-2, TGF-ß1 and ICAM-1 proteins secreted into the supernatant were measured by ELISA assay. RESULTS: Macrophages cultured on nanotube layers had spread out morphology, the largest (120 nm) nanotube layer eliciting an elongation by 24 h. Macrophages adhered significantly less to 120 nm TiO2 nanotubes than to control discs at 4 h after application; after 24 h incubation, macrophages were sufficiently viable (P < 0.05) on 30 and 70 nm nanotube layers. Increasing nanotube diameter led to increased BMP-2 protein secretion and increased BMP-2 mRNA expression. CONCLUSION: These results demonstrate that nanoscale topography of TiO2 nanotube layers can affect macrophage morphology, adhesion, viability and BMP-2 expression. Macrophages grown on layers of large nanotubes had the highest potential to enhance bone formation during bone healing.

Resection with total caudate lobectomy confers survival benefit in hilar cholangiocarcinoma of Bismuth type III and IV.

PURPOSE: To identify prognostic predictors for overall survival of patients with hilar cholangiocarcinoma of Bismuth type III and IV (HCBT34), and to determine survival benefit and safety of total caudate lobectomy (TCL) in a Chinese centre. METHODS: From January 2001 to December 2010, 171 patients with the diagnosis of HCBT34, who underwent a potentially curative resection, were included in this study. Cox proportional hazards regression models were used to determine the association between possible prognostic variables and survival time. Curative resectability rate, morbidity and mortality were investigated also. RESULTS: Resection with TCL was significantly associated with more opportunity to achieve curative resection (p < 0.01), did not accompany with more morbidity (p = 0.39) and mortality (p = 0.67). Cox regression analysis demonstrated positive resection margins [Relative Risk (RR) 3.6, 95% CI 3.5-3.7], not well differentiation (RR 2.9, 95% CI 2.7-3.1), higher preoperative serum peak CA19-9 level (RR 1.6, 95% CI 1.5-1.7) and regional lymph nodes involvement (RR 1.5, 95% CI 1.4-1.6) as independent adverse prognostic variables. CONCLUSIONS: Resection with TCL offers a long-term survival opportunity for HCBT34, with high curative resectability rates and an acceptable safety profile.

The influence of bone cement type on production of fretting wear on the femoral stem surface: a preliminary study.

BACKGROUND: It has been reported that bone cement correlates with survivorship of cemented total hip replacement. However, little research has been published to investigate the influence of bone cement type on production of fretting wear on the femoral stem. METHODS: In the present study, we performed six in vitro wear simulations using the same type of femoral stem (polished Exeter V40™) and three different bone cements (Simplex P, Palacos R, and CMW 3). FINDINGS: Fretting wear was consistently reproduced on the stem surface and the wear locations compared well with the results of retrieval studies. Selected 3D surface parameters were utilised to quantitatively evaluate fretting wear and no significant difference was identified in terms of fretting wear severity between these simulations. The bone cements were all badly damaged in those sites contacting the fretting wear areas on the femoral stem. Additionally, there were plenty of wear debris present on the cement surface, and the energy dispersive X-ray analysis confirmed that it was just cement particles for Simplex P bone cement, whilst it included metallic particles for Palacos R and CMW 3 bone cements. INTERPRETATION: This preliminary study shed some light on the influence of bone cement type on production of fretting wear on the femoral stem surface but further research is needed to gain a better understanding on this issue.

Clinical features and risk factors of creatine kinase elevations and myopathy associated with telbivudine.

With the extensive use of telbivudine, more and more studies reported its association with creatine kinase (CK) elevations and myopathy. However, clinical features of these adverse effects were poorly understood. The aim of the present study was to investigate the clinical features and risk factors of CK elevations and myopathy associated with telbivudine. The serum CK levels of 200 patients who were treated with telbivudine for chronic hepatitis B (CHB) between January 2007 and July 2010 were monitored and analysed along with clinical manifestations. The 3-year cumulative incidence of CK elevations and myopathy was 84.3% and 5%, respectively. CK elevations occurred more frequently in men than in women, and patients aged ≤45 years and with negative HBeAg had higher incidence of CK elevations. There was no difference in CK elevations among patients with different HBV DNA levels. Male, younger age and HBeAg negativity were independent predictors of CK elevations by multivariate Cox regression analysis. There was no association between the occurrence of myopathy and variables including age, sex, HBeAg and HBV DNA. No risk factors of myopathy were identified. CK elevations usually occurred 21 months after starting treatment, and most patients resolved spontaneously without interruption of telbivudine therapy except three patients who had to switch to other agents. In conclusion, CK elevations are common adverse reactions associated with telbivudine therapy, while myopathy is rare. Male, younger age and HBeAg negativity might be risk factors of CK elevations.

Ectopic study of tissue-engineered bone complex with enamel matrix proteins, bone marrow stromal cells in porous calcium phosphate cement scaffolds, in nude mice.

OBJECTIVE: This study aimed to investigate the potential of enamel matrix proteins (EMPs) on promoting osteogenic differentiation of porcine bone marrow stromal cells (pBMSCs), as well as new bone formation capabilities, in a tissue-engineered bone complex scaffold of EMPs, pBMSCs and porous calcium phosphate cement (CPC). MATERIALS AND METHODS: Effects of EMPs on pBMSCs in vitro was first determined by alkaline phosphatase (ALP) activity, von Kossa staining assay and mRNA expression of ALP, bone sialoprotein (BSP) and osteocalcin (OCN) genes. Next, an ectopic new bone formation test was performed in a nude mouse model with four groups: CPC scaffold alone; CPC scaffold + EMPs; CPC scaffold + pBMSCs; and CPC scaffold + EMPs + pBMSCs, for 2 or 4 weeks. RESULTS: ALP activity, von Kossa assay and mRNA expressions of ALP, BSP and OCN genes were all significantly higher with 150 µg/ml EMP treatment in vitro. In nude mice, new bone formation was detected only in the CPC scaffold + EMPs + pBMSCs group at 2 weeks. At 4 weeks, in the tissue-engineered construct there was significantly higher bone formation ability than other groups. CONCLUSIONS: EMPs promoted osteogenic differentiation of pBMSCs, and the tissue-engineered complex of EMPs, pBMSCs and CPC scaffold may be a valuable alternative to be used in periodontal bone tissue engineering and regeneration.