Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

Safety and immunogenicity of a heterologous boost with a recombinant vaccine, NVSI-06-07, in the inactivated vaccine recipients from UAE: a phase 2 randomised, double-blinded, controlled clinical trial

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

Influence of base materials on stress distribution in endodontically treated maxillary premolars restored with endocrowns / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the influence of base materials on stress distribution in endodontically treated maxillary premolars restored with endocrowns using three-dimensional finite element analysis.@*METHODS@#A maxillary second premolar was scanned by Micro-CT and a three-dimensional finite element model of ceramic endocrown with 1 mm thickness of base was established. A model without base was also established as a negative control. Four kinds of conventional base materials with different elastic modulus were adopted: light cure glass ionomer(3M Vitrebond, 3 657 MPa), flowable composite resin(3M Filtek Z350XT Flowable Restorative, 7 300 MPa), high strength glass ionomer(GC Fuji Ⅸ, 13 130 MPa), and posterior composite resin(3M Filtek P60, 19 700 MPa). With a 200 N force loaded vertically and obliquely, the distribution and magnitude of stress in the tooth tissue and adhesive layer were investigated by three-dimensional finite element analysis.@*RESULTS@#The maximum von Mises stress values(vertical/oblique) in dentin and adhesive layer were measured as follows: (1) no base material: 19.39/70.49 MPa in dentin and 6.97/17.97 MPa in adhesive layer; (2) light cure glass ionomer: 19.00/69.75 MPa in dentin and 6.87/16.30 MPa in adhesive layer; (3) flowable composite resin: 18.78/69.33 MPa in dentin and 6.79/16.17 MPa in adhesive layer; (4) high strength glass ionomer: 18.71/69.20 MPa in dentin and 6.74/16.07 MPa in adhesive layer; (5) posterior composite resin: 18.61/69.03 MPa in dentin and 6.70/16.01 MPa in adhesive layer. Under the same loading condition, models with different elastic moduli of base materials had similar stress distribution patterns. The von Mises stress of tooth tissue was mainly concentrated in the tooth cervix. Under oblique load, the regions where von Mises stress concentrated in were similar to those under a vertical load, but the values increased. The stress concentration in the tooth cervix was alleviated in models with base materials compared with the model without base material. The maximum von Mises stress in the tooth tissue and adhesive layer decreased when the elastic modulus of base materials increased and got close to that of dentin.@*CONCLUSION@#The posterior composite resin of which the elastic moduli is high and close to that of dentin is recommended as base material for premolar endocrowns to alleviate the concentration of stress in tooth cervix and adhesive layer.

Evaluation of wear property of Giomer and universal composite in vivo / 北京大学学报(医学版)

OBJECTIVE@#To observe the wear performance of Giomer and universal composite for posterior restorations by 3D laser scan method, in order to guide the material selection in clinic.@*METHODS@#In this study, 48 patients (108 teeth) were selected according to the inclusion and exclusion criteria. All the patients in need of a minimum of 2 Class Ⅰ and/or Class Ⅱ restorations were invited to join the study. The teeth were restored with Giomer (Beautifil Ⅱ, BF) and universal composite (Filtek Z350, Z350) randomly. The restorations were evaluated at baseline and after 6-, 18-, 48-month using the modified United States Public Health Service (USPHS) criteria for clinical performance. The in vivo images and gypsum replicas were taken at each recall. A 3D-laser scanner and Geomagic Studio 12 were used to analyze the wear depth quantitatively. Statistical analysis was performed with SPSS 20.0.@*RESULTS@#After 4 years, 89.6% patients were recalled. The survival rate of both materials was 95.8% (Kaplan-Meier survival analysis). Seven restorations of the two materials failed due to loss of restoration, bulk fracture, secondary caries and pulp necrosis. The wear patterns of restorations were divided into 2 classes. Pattern Ⅰ: occlusal contact areas showed the deepest and fastest wear depth; pattern Ⅱ: the wear depth was slow and uniform. Both materials showed a rapid wear in the first 6 months. Then the wear rate was decreased. The occlusal wear depth after 4 years were (58±22) μm and (54±16) μm for BF group and Z350 group respectively, which were in accordance with the American Dental Association (ADA) guidelines (wear depth for 3 years < 100 μm). No significant differences (P>0.05) were observed between the two groups. Regarding the restorations with wear pattern Ⅰ, the wear depth of BF group was higher than Z350 group at 6- and 48-month (P < 0.05), while there was no significant difference between restorations with wear pattern Ⅱ (P>0.05).@*CONCLUSION@#Within the limitation of the study, after 4 years, the survival rate and wear resistance of Giomer met ADA guidelines for tooth-colored restorative materials for posterior teeth. When the two materials were applied in occlusal contact areas, wear resistance of Giomer was slightly lower than universal composite resin. No significant difference was found when they were applied in none of the occlusal contact areas.

Evaluation of microtensile bond strength between resin composite and glass ceramic / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the microtensile bond strength of resin composite to glass ceramic, and the effect of surface treatment of resin composite and thermal cycling aging on the microtensile bond strength.@*METHODS@#Rectangular blocks were made with dentin of extracted molars, resin composite or feldspathic glass ceramic respectively. The bonding surfaces of these rectangular blocks were sanded by 600-grit silicon carbide paper before luting. A self-etching resin cement was used as luting agent. The specimens were divided into groups according to the types of substrates of adhesion (dentin/glass ceramic or resin composite/glass ceramic), the way of surface treatments and whether thermal cycling aging ocurred. The dentin blocks were adhered to ceramic blocks as controls (group A1 and A2). The resin composite blocks were adhered to the ceramic blocks as experiment groups. The resin composite surfaces were treated by different ways before luting: no extra surface treatment (group B1 and B2), treated by ethyl methacrylate solution (group C1 and C2) or silane coupling agent (group D1 and D2), coarsened by 360-grit silicon carbide paper (group E1 and E2) or polished by 1 200-grit silicon carbide paper (group F1 and F2). After luting, the microtensile bond strength of the specimens were tested before (group A1-F1) or after (group A2-F2) thermal cycling aging. After microtensile bond strength test, the fracture bonding surfaces of the specimens were observed by a scanning electron microscopy to determine the type of bonding failure. The data were statistically analyzed using one-way analysis of variance.@*RESULTS@#The microtensile bond strength of resin composite to glass ceramic with no extra treatment achieved high bond values before and after thermal cycling [B1 (30.02±3.85) MPa, B2 (26.83±3.14) MPa], which were statistically different from those of the control groups [A1 (20.55±4.51) MPa, A2 (12.94±0.69) MPa, P < 0.05]. The microtensile bond strength between the glass ceramic and resin composite did not increase after different surface treatments of resin composite.@*CONCLUSIONS@#The microtensile bond strength between resin composite and glass ceramic achieved as similar bond strength as that between dentin and glass ceramic and even better. Surface treatment of resin composite via methyl methacrylate solution, silane coupling agent, coarsening, or polishing did not increase the microtensile bond strength effectually.

Nano-sized bioactive glass enhances osteogenesis of critical bone defect in rabbits / 北京大学学报(医学版)

OBJECTIVE@#To compare the osteogenic effects of a nano-sized 58S bioactive glass (nano-58S BG) and a traditional 45S5 bioactive glass(45S5 BG) in penetrating parietal critical bone defects.@*METHODS@#Critical bone defect with 9 mm diameter was created in the parietal bone of New Zealand rabbits. The bone defects were then filled with either nano-58S BG, or 45S5 BG, or nothing but the newly-formed blood clot as the blank control at random. For histological observation, specimens were gained 4 and 8 weeks after the surgery, sectioned and stained by HE. The amount of collagen type I was observed with Picric-Sirius Red staining through polarimetry. To observe the new bone formation with fluorescence under the laser confocal microscope, we injected fluorescent markers 14, 28, and 42 days after the surgery. The markers were tetracycline hydrochloride, alizarin red and calcin individually in chronological order. Image J software was used to quantify the bone regeneration.@*RESULTS@#HE staining showed that BG particulates were integrated with the surrounding tissue without any inflammatory cells infiltration 4 weeks after surgery. New bone regeneration was observed both from the border and in the center of the defects in both BG groups. No bone regeneration in defect center was observed in control group. At the end of 8 weeks, there was more bone regeneration in nano-58S group compared with 45S5 group and control group. The structure of the new bone in BG groups was hollow, which was similar to the natural normal parietal bone. No hollow structure was observed in the new bone of control group. Picric-sirius Red polarimetry showed that more amount of collagen type I was found in nano-58S group than in either 45S5 or control group. The fluorescent observation of the hard tissue slices at the end of 8 weeks showed statistically larger scope and faster new bone formation in nano-58S group with (29.4±4.48) μm thickness from 4-6 weeks and (35.3±3.74) μm from 6-8 weeks compared with 45S5 group [(13.43±3.44) μm and (17.64±4.13) μm] and control group [(5.88±2.92) μm and (6.07±3.02) μm, P<0.01].@*CONCLUSION@#Compared with the traditional 45S5 bioactive glass, 58S nano-sized bioactive glass showed better osteogenic effect in bone regeneration in parietal bones of rabbits.

Detection of root cracks after root canal preparation using rotary NiTi systems by optical coherence tomography (OCT) scan / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the accuracy of optical coherence tomography (OCT) in detecting root cracks after root canal instrumentation using histological gold standard.@*METHODS@#Twenty complete extracted human mandibular incisors that were free of caries, calculus, and root treatment were chosen and accessed coronally with a diamond bur, then mounted in resin blocks with alginate impression material using simulated periodontal ligaments, and the apex was exposed 3 mm. The teeth were stored in water at room temperature. Then the teeth were then instrumented to the major apical foramen (AF) at #30/0.09 using ProTaper Universal rotary nickel titanium system (Dentsply Maillefer, Ballaigues, Switzerland), irrigation with 1% sodium hypochlorite (NaOCl) by using a 26-gauge needle followed after each instrument. The apical root was scanned with 360° of rotation by Swept-Source Optical Coherence Tomography (SS-OCT) (wavelength: 1 310 nm, scan rate: 20 kHz, axial resolution: 16 μm) with driving device (stepper motor and lifting platform). The reconstruction images of axial planes 1, 2 and 3 mm from the apex were examined and the root cracks were blindly diagnosed by two observers. The horizontal section was performed at 1, 2 and 3 mm from the apex using low speed disc saw (Leica SP1600, Wetzlar, Germany). The presence of cracks was noted under an optical stereomicroscope (ZOOM-630E) with a cold light source using as gold standard to evaluate the accuracy of OCT in detecting root cracks after root canal instrumentation.@*RESULTS@#After canals instrumentation with ProTaper Universal rotary nickel titanium system to #30/0.09, root cracks were detected in 9 of 20 teeth by histological examination. Crack lines were observed on 13 of 60 horizontal sections and cracks on 12 of the 13 sections were detected by OCT. No cracks were observed in the other 47 of the 60 horizontal sections,none of which was misdiagnosed by OCT. The overall accuracy rate for detection of root cracks with OCT was 0.983, the sensitivity was 0.923, the specificity was 1.000, the positive predictive value (PPV) was 1.000 and the negative predictive value (NPV) was 0.979.@*CONCLUSION@#OCT may be a promising nondestructive imaging method for diagnosing root canal cracks after canal instrumentation.

Efficacy and safety of levetiracetam for adult seizure: A randomized controlled trial / 第二军医大学学报

Objective To evaluate the efficacy and safety of levetiracetam (LTA) for adult seizure (AS). Methods A randomized, double-blinded, double-dummy, positive drug controlled trial was conducted. One hundred and twenty eligible AS patients were randomly divided into two groups: intervention group and control group, with 60 in each group. Patients in the intervention group received LTA tablet plus valproate sodium mimetic tablet, and patients in the control group received valproate sodium tablet and LTA mimetic tablet. The treatment course was 26 weeks in both groups, and the patients was followed up for 3 months after the treatment. The outcomes included total efficacy rate, weekly epilepsy seizure frequency, seizure duration, quality of life (measured by QOLIE-31 Scale) and adverse events related to drugs after 1-3 days of treatment and at 3 months of follow-up. Results The weekly epilepsy seizure frequency, seizure duration and QOLIE-31 score were not significantly different between the two groups before treatment. The total efficacy rates after treatment and at 3 months of follow-up in the intervention group were 95. 0% (57/60) and 91 7% (55/60), respectively, and were significantly higher than those in the control group of 71 7% (43/60) and 63. 3% (38/60) (P<0 01). The weekly epilepsy seizure frequency, seizure duration and QOLIE-31 score after treatment and at 3 months of follow-up were significantly different as compared with before treatment in both groups (P<3. 01); and there were significantly different between the two groups (P<3 01). The adverse events after treatment were similar between both groups. Conclusion The efficacy of LAT is superior to the valproate sodium tablet for AS, with the less toxicity, and it can be clinical drug of choice for AS.

Effect of bioactive glasses on angiogenic growth factors of human dental pulp cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of bioactive glasses (BG) including 45S5 and nano-58S on proliferation, angiogenic markers vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) secretion and gene expression of human dental pulp cells (HDPC).</p><p><b>METHODS</b>HDPC of 4th passage were cultured in Dulbecco's modified Eagle's medium (DMEM) which contained 0.1 g/L 45S5 or nano-58S ionic dissolution products. Meanwhile HDPC were cultured in DMEM without BG as control group. Proliferation of the cells was evaluated with methyl thiazolyl tetrazolium (MTT) assay on day 1, 2, 3. Quantitative real-time PCR and quantitative sandwich enzyme immunoassays were used to test VEGF and bFGF gene expression and protein secretion of HDPC on day 1, 2, 3.</p><p><b>RESULTS</b>The relative growth rate (RGR) of 45S5 and nano-58S groups were (134.5 ± 5.0)% and (146.3 ± 19.8)%, which was significantly different from that of control group (P < 0.05). The quantity of VEGF secretion of two experimental groups were (189.29 ± 4.64) and (216.18 ± 14.67) ng/L, respectively, significantly higher than that of the control group [(159.03 ± 11.69) ng/L] (P < 0.05). Furthermore, the nano-58S group secreted much more VEGF than 45S5 group (P < 0.05).bFGF secretion of HDPC was also enhanced by both 45S5 and nano-58S bioactive glasses. The VEGF gene expression of 45S5 and nano-58S on day 1 were (1.70 ± 0.19) and (1.63 ± 0.42), while the bFGF gene expressin on day 3 were (1.49 ± 0.02) and (2.30 ± 0.04), all significantly higher than that of control group (P < 0.05).</p><p><b>CONCLUSIONS</b>Bioactive glasses can enhance the proliferation, VEGF and bFGF secretion and gene expression of human dental pulp cells. Compared with 45S5, nano-58S showed a higher activation.</p>

The durability of three self-etch adhesives bonded to dentin / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the durability of self-etch adhesives bonded to dentin in vitro.</p><p><b>METHODS</b>Forty-two extracted human molars were selected and occlusal dentin surfaces were exposed. The teeth were randomly distributed into three groups based on adhesives applied. The one-step self-etch adhesive B(Adper Prompt) and C(G-Bond) and two-step self-etch adhesive A (Clearfil SE bond) were used. After application of the adhesives to the dentin surfaces, composite crowns were built up, after 24 h water storage, the teeth were sectioned longitudinally into sticks (1.0 mm×1.0 mm bonding area) for microtensile testing or slabs (1 mm thick) for scanning electron microscopec (SEM) observation. Bonding strength (mTBS) and nano-leakage were evaluated immediately after cutting or after 6 months in water. The mTBS was analyzed using one-way ANOVA (SPSS 13.0). The nanoleakage was observed by SEM with a backscattered electron detector.</p><p><b>RESULTS</b>Both adhesives and water storage time affected the mTBS. All adhesives showed decreased bond strength after six-month water aging [A dropped from (40.60 ± 5.76) MPa to (36.04 ± 3.15) MPa; B dropped from (19.06 ± 1.50) MPa to (11.19 ± 1.97) MPa; C dropped from (17.75 ± 1.10) MPa to (9.14 ± 1.15) MPa] (P < 0.05). B and C showed lower mTBS than A after aging (P < 0.05). Compared to A, nanoleakage was more obvious after aging for B and C.</p><p><b>CONCLUSIONS</b>All self-etch adhesives tested were probably influenced by water aging, however, the two-step adhesive showed better durability than the one-step adhesives.</p>

Expression patterns of amelogenin and enamelin in developing mouse tooth germs / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To invesitgate the expression patterns of amelogenin and enamelin in the developing tooth germs.</p><p><b>METHODS</b>Mandible sections of postnatal day 1, 3, 7 and 14 mouse were prepared, immunohistochemical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) were performed to detect the expression patterns of amelogenin and enamelin in mandibular first molars.</p><p><b>RESULTS</b>Amelogenin was observed in the cytoplasm of secretory ameloblasts and the whole enamel matrix layer. It was also transiently expressed in the odontoblasts of postnatal day 1 molars. Enamelin proteins were observed in the enamel layer deposited by secretory ameloblasts, especially intense beneath the ameloblast process and dentino-enamel junction. The mRNA levels of both amelogenin and enamelin were highest on postnatal day 7 (the ratio to glyceraldehyde phosphate dehydrogenase of amelogenin and enamelin: 0.813 ± 0.085 and 0.799 ± 0.064, respectively, P < 0.05).</p><p><b>CONCLUSIONS</b>Amelogenin and enamelin were enamel matrix proteins predominately expressed by secretory ameloblasts. The temporal-spatial expression patterns of amelogenin and enamelin indicate the important roles they played in amelogenesis and biomineralization.</p>

Characterization of Streptococcus oligofermentans sucrose metabolism demonstrates reduced pyruvic and lactic acid production / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Streptococcus (S.) oligofermentans is a newly identified bacteria with a yet to be defined mechanism of sucrose metabolism that results in acid production. This study aimed to investigate the biochemical mechanisms of S. oligoferm-entans glucose metaolism.</p><p><b>METHODS</b>The S. oligofermentans LMG21532, Lactobacillus (L.) fermentum 38 and the S. mutans UA140 were used to characterize sucrose metabolism by measuring lactate dehydrogenase (LDH) activity and lactic acid production. Continuous dynamics and high performance capillary electrophoresis were used to determine LDH activity and lactic acid production, respectively, from bacteria collected at 0, 10 and 30 minutes after cultured in 10% sucrose.</p><p><b>RESULTS</b>These analyses demonstrated that LDH activity of the three bacterial strains examined remained stable but significantly different throughout the sucrose fermentation process. The S. oligofermentans LDH activity ((0.61 ± 0.05) U/mg) was significantly lower than that of L. fermentum ((52.91 ± 8.97) U/mg). In addition, the S. oligofermentans total lactate production ((0.048 ± 0.021) mmol/L) was also significantly lower than that of L. fermentum ((0.958 ± 0.201) mmol/L). Although the S. oligofermentans LDH production was almost double of that produced by S. mutans ((0.32 ± 0.07) U/mg), lactic acid production was approximately one sixth that of S. mutans ((0.296 ± 0.058) mmol/L). Additional tests examining pyruvic acid production (the LDH substrate) demonstrated that lactic acid concentrations correlated with pyruvic acid production. That is, pyruvic acid production by S. oligofermentans was undetectable following sucrose incubation, however, (0.074 ± 0.024) and (0.175 ± 0.098) mmol/L pyruvic acid were produced by S. mutans and L. fermentum, respectively.</p><p><b>CONCLUSION</b>S. oligofermentans is incapable of fermenting carbohydrates to produce enough pyruvic acid, which results in reduced lactic acid production.</p>

Relationship between Sp3 and the transcriptional regulation of enamelin gene / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the role of Sp3 in the transcriptional regulation of enamelin gene.</p><p><b>METHODS</b>By bioinformatic analysis, a putative responsive element for Sp3 was identified. Electrophoretic mobility shift assay was used to examine the interaction between Sp3 and enamelin. 5'-flanking regulatory region of enamelin was cloned and ligated into pGL3-basic luciferase vector. Sp3 and the Enam-luc were cotransfected into mouse ameloblast-like cell line, and the activity of luciferase was examined.</p><p><b>RESULTS</b>The results showed that Sp3 could not directly bind to the enamelin regulation region and activate enamelin transcription.</p><p><b>CONCLUSIONS</b>Sp3 might not be involved in transcriptional regulation of enamelin gene via an indirect interaction.</p>

Evaluation of adaptation of root canal filled with three obturation techniques in vitro / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the adaptation of root canal filled with three obturation techniques in vitro.</p><p><b>METHODS</b>Fifty-seven cleaned and shaped premolars were divided into three groups, each group including 10 single root canal premolars and 9 double root canal premolars, and filled respectively with following techniques: GuttaFlow paste with single master cone (GF group), cold lateral compaction technique with AH plus sealer (LC group), warm vertical compaction technique with AH plus sealer (VC group). The roots were invested and sectioned at 1 mm interval from crown to apex using a microtome saw under water cooling. Both surfaces of the sections were digitally photographed and measured using a stereomicroscope. The number of sections with voids and the area of voids were measured and analyzed.</p><p><b>RESULTS</b>The frequency of sections with voids: VC group (21.4%, 76/355) was significantly lower than GF group (47.7%, 173/363) and LC group (52.6%, 190/361), P < 0.0167. There was no significant difference between GF and LC group (P > 0.0167). The percentage of voids area (AV%): GF group was significantly higher than LC and VC group (P = 0.000, P = 0.008). The median of GF group was 2.67, LC group was 1.55, VC group was 1.01. No significant difference between VC and LC group (P = 0.076). The filling quality of isthmus: 86% (85/99) isthmus were well filled in VC, significantly higher than GF group (55%, 43/78) and LC group (58%, 49/84), P < 0.0167. There was no significant difference between GF and LC group (P > 0.0167).</p><p><b>CONCLUSIONS</b>The adaptation of root canal filled with warm vertical compaction technique was superior to cold lateral compaction technique and GuttaFlow technique.</p>

Evaluation of shear bond strengths of self-etching and total-etching dental adhesives to enamel and dentin / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the shear bond strengths of four dental adhesives in vitro.</p><p><b>METHODS</b>The facial surfaces of 20 human maxillary incisors were prepared to expose fresh enamel and randomly divided into four groups, in each group 5 teeth were bonded with one adhesives: group A (Clearfil Protect Bond, self-etching two steps), group B (Adper( Prompt, self-etching one step), group C (SwissTEC SL Bond, total-etching two steps), group D (Single Bond, total-etching two steps). Shear bond strengths were determined using an universal testing machine after being stored in distilled water for 24 h at 37 degrees C.</p><p><b>RESULTS</b>The bond strengths to enamel and dentin were (25.33 +/- 2.84) and (26.07 +/- 5.56) MPa in group A, (17.08 +/- 5.13) and (17.93 +/- 4.70) MPa in group B, (33.14 +/- 6.05) and (41.92 +/- 6.25) MPa in group C, (22.51 +/- 6.25) and (21.45 +/- 7.34) MPa in group D. Group C showed the highest and group B the lowest shear bond strength to enamel and dentin among the four groups.</p><p><b>CONCLUSIONS</b>The two-step self-etching adhesive showed comparable shear bond strength to some of the total-etching adhesives and higher shear bond strength than one-step self-etching adhesive.</p>

Effects of application methods of self-etching adhesives on resin-dentin bonding / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of application time and rubbing action of self-etching adhesives on resin-dentin bond strength and interface morphology in vitro.</p><p><b>METHODS</b>Caries-free human third molars were wet ground to expose dentin surface. Three self-etching bonding agents were applied with varying application time and with/without rubbing. The microtensile bond strength and interface morphology were evaluated.</p><p><b>RESULTS</b>When etching time was shortened, normal and prolonged, the bond strength was bonding agent 1 (Adper Prompt): (16.30 +/- 2.59), (23.13 +/- 2.56), (22.28 +/- 2.83) MPa, bonding agent 2 (Xeno III): (15.17 +/- 6.07), (34.50 +/- 3.64), (24.87 +/- 7.01) MPa, bonding agent 3 (Clearfil SE Bond): (29.92 +/- 3.32), (42.21 +/- 6.28), (41.07 +/- 3.93) MPa. When etching was applied with and without rubbing, the bond strength was bonding agent 1 (23.13 +/- 2.56), (12.53 +/- 3.73) MPa, bonding agent 2 (23.98 +/- 3.86), (34.50 +/- 3.64) MPa, bonding agent 3 (48.37 +/- 4.95), (42.21 +/- 6.28) MPa.</p><p><b>CONCLUSIONS</b>Shortening application time decreased bond strength of self-etching adhesives, while prolonging application time did not increase bond strength of self-etching adhesives. Not all self-etching adhesives applied with rubbing showed increased bond strength to dentin, which is product-dependent. Manufactures' instructions should be followed to achieve optimum bonding.</p>

Analysis of short chain fatty acids in gingival crevicular fluid of patients with aggressive periodontitis / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate 7 short chain fatty acids (SCFA) concentrations in gingival crevicular fluid (GCF) of aggressive periodontitis (AgP) and to analyze the relationship between levels of SCFA and AgP clinical parameters.</p><p><b>METHODS</b>GCF was collected from 152 sites of 38 AgP patients and 56 sites of 14 healthy subjects. Formic acid, succinic acid, acetic acid, lactic acid, propionic acid, butyric acid and isovalerianic acid were detected by high performance capillary electrophoresis.</p><p><b>RESULTS</b>The concentrations of succinic acid, acetic acid, lactic acid, propionic acid, butyric acid and isovalerianic acid in GCF were significantly higher in AgP patients than in healthy group, while formic acid was lower in GCF of AgP group compared with healthy group. Correlation analysis showed that formic acid was negatively correlated with bleeding index (BI), probing depth (PD) and attachment loss (AL), while BI was positively correlated with succinic acid, acetic acid, lactic acid, propionic acid and butyric acid; PD and AL were positively correlated with succinic acid, acetic acid, propionic acid, butyric acid and isovalerianic acid.</p><p><b>CONCLUSIONS</b>The elevation of succinic acid, acetic acid, propionic acid, butyric acid and isovalerianic acid concentrations in GCF may be related with AgP destruction condition, while formic acid concentration was reduced.</p>

Assessment of shaping ability of ProTaper in curved canals / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate shaping ability of nickel-titanium rotary instruments (ProTaper) in curved root canals.</p><p><b>METHODS</b>The computer assistant measure system of simulated root canal was used for quantitative analysis of root shape of eight simulated root canals during ProTaper shaping process. Blue ink was injected into the simulated root canals before instrumentation, when F2 reached work length(WL) (F2) and when F3 reached WL(F3). Orifices and apexes were sealed with adhesive tapes. Root canal images were gained by Mustek BP4800TA scanner. The images before and after preparation were turned into Di-numerical images and fused. The changes of central line positions and curvatures were measured in quantity through this system. Data of seven preestablished point from orifice to apex were recorded and analysed by SPSS 10.0 soft ware.</p><p><b>RESULTS</b>ProTaper system reduced the angles of simulated canals. Selecting F2 or F3 as the master apical file (MAF) had no influence on the changing rate of the root angles. ProTaper had excess cutting on the outer wall of orifice and the inner wall of curve part, but the displacement of apex was minimal (only 0.021 mm).</p><p><b>CONCLUSION</b>ProTaper has preferable shaping ability. To prepare very difficult curved canals, the master apical file (MAF) could be F3. Attention should be taken when preparing some curved canals with hollows in their inner walls, in order to avoid the lateral perforation.</p>

Comparison of antimicrobial efficacy of four endodontic irrigants using an in vitro model infected by Enterococcus faecalis / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To compare the antimicrobial efficacy of four endodontic irrigants using an in vitro model infected by Enterococcus faecalis (Ef).</p><p><b>METHODS</b>The root canals of fifty extracted teeth were infected by Ef in vitro. The test groups were irrigated with 3% H(2)O(2), 2.5% sodium hypochlorite (SH), 2% chloramine-T (CR), and 2% chlorhexidine (CHX), respectively, and the control group was irrigated with 0.9% NaCl. The concentration of Ef in canals of each group was calculated before and after irrigation. The residual bacteria within the dentinal tubules and vitalities of the residual bacteria were also examined.</p><p><b>RESULTS</b>All chemical irrigants were significantly more effective than 0.9% NaCl (P < 0.05); 2.5% SH and 2% CHX were statistically more effective than 3% H(2)O(2) (P < 0.05). Residual bacteria could be found in the dentinal tubules and propagated 72 h after.</p><p><b>CONCLUSIONS</b>2% CR and 2% CHX had almost the equivalent antimicrobial effect as 2.5% SH, but 3% H(2)O(2) was less effective.</p>