The effect of thymopentin add-on in hepatitis B e antigen positive chronic hepatitis B after virus suppression by peginterferon plus entecavir therapy.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) was positively correlated with serological hepatitis B surface antigen (HBsAg) levels in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients. We evaluated whether Thymopentin (TP5) and interferon (IFN-a) had a synergic effect on HBV cccDNA and the effect of TP5 addition therapy on HBsAg clearance in CHB patients. Real-time PCR experiments were performed to test cccDNA in HepG2.2.15 cells. 45 HBeAg-positive CHB patients had been distributed into two groups randomly. Treatment group: 23 patients were treated with a 24-week TP5 on the basis of the treatment entecavir (ETV) and peginterferon alfa-2a (PegIFN alpha-2a). Control group: 22 patients were treated with ETV and PegIFNa-2a. The study period was 72 weeks. In HepG2.2.15 cells, TP5 5ug/ml and 10ug/ml respectively combined with IFN-a 2ku/ml could potently inhibit cccDNA level at 72 hours (P<0.05). In clinical study, mean HBsAg levels in two groups are not significantly different at different time points (p=0.112). However, changes of mean HBsAg levels in TP5 add-on group at different time points are significantly different (p<0.05). Patients with HBsAg levels <1500IU/ml in control group had higher HBsAg levels compared with patients with HBsAg levels <1500IU/ml in TP5 add-on group (P=0.019). The latter had the most pronounced HBsAg reduction. TP5 and IFN had a synergic effect on inhibiting cccDNA levels in HepG2.2.15 cells; Patients in treatment group showed no extra side effects compared with the control group. 24 weeks TP5 add-on treatment was safe and had a tendency to accelerate the decline of HBsAg when HBV-DNA was undetectable.

Lipase-triggered drug release from BCL2 inhibitor ABT-199-loaded nanoparticles to elevate anti-leukemic activity through enhanced drug targeting on the mitochondrial membrane.

Selective BCL2 inhibitor ABT-199 has been approved to treat hematological malignancies including acute myeloid leukemia (AML). However, acquired drug resistance and severe side effects occur after extended treatment limiting the clinical usage of ABT-199. Here, we successfully encapsulated pure ABT-199 in amphiphilic mPEG-b-PTMC169 block copolymer, forming mPEG-b-PTMC169@ABT-199 nanoparticles (abbreviated as PEG-ABT-199), which presented better aqueous dispersion and higher efficiency of loading and encapsulation than pure ABT-199. We then compared the anti-leukemic ability of pure ABT-199 and PEG-ABT-199 in vitro and in vivo. PEG-ABT-199 had a lower IC50 value compared with pure ABT-199 in MV4-11 and MOLM-13 cell lines. In addition, PEG-ABT-199 significantly induced apoptosis and decreased colony number than pure ABT-199. Most importantly, PEG-ABT-199 markedly reduced leukemic burden, inhibited the infiltration of leukemic blasts in the spleen, and extended the overall survival (OS) in MLL-AF9-transduced murine AML compared with free ABT-199. Meanwhile, the blank PEG169 NP was non-toxic to normal hematopoiesis in vitro and in vivo, suggesting that PEG169 NP is a safe carrier. Mechanistically, PEG-ABT-199 enhanced mitochondria-targeted delivery of ABT-199 to trigger the collapse of mitochondrial membrane potential (MMP), the release of cytochrome c (cyt-c), and mitochondria-based apoptosis. In conclusion, our results suggest that PEG-ABT-199 has more vital anti-leukemic ability than pure ABT-199. PEG-ABT-199 has potential application in clinical trials to alleviate side effects and improve anti-leukemia ability. STATEMENT OF SIGNIFICANCE: ATB-199, an orally selective inhibitor for BCL2 protein, presents marked activity in relapsed or refractory AML, T-ALL, and CLL patients. However, ABT-199 resistance severely limits the further clinical usage because of off-target effects, non-specific toxicities, and low delivery of drugs. To reduce the side-effects and improve the solubility and bioavailability, ABT-199 was encapsulated into the amphiphilic mPEG-b-PTMC block copolymer by co-assembly method to obtain mPEG-b-PTMC@ABT-199 nanoparticles (PEG-ABT-199). PEG-ABT-199 has several advantages compared with pure ABT-199. 1.PEG-ABT-199 presents better aqueous dispersion and higher efficiencies of loading and encapsulation than pure ABT-199. 2. PEG-ABT-199 substantially enhances the anti-leukemic ability in vitro and in vivo compared with pure ABT-199. 3. PEG-ABT-199 has little effects on normal cells. 4. PEG-ABT-199 can reduce treatment cost.

Influence of varied surface texture of dentin porcelain on optical properties of porcelain specimens.

STATEMENT OF PROBLEM: Differences in the texture of dentin porcelain surfaces may change the direction of incident light at the enamel-dentin porcelain interface and affect the optical properties of a ceramic crown. PURPOSE: The purpose of this study was to measure optical parameters of enamel-dentin porcelain complexes with different dentin porcelain surface textures, and to analyze the relationship between optical parameters and surface texture. MATERIAL AND METHODS: Eighty dentin porcelain (ShoFu Vintage Halo, shade A2) disks (1.0 × 10.0 mm) were fabricated and assigned to 10 groups (n=8). The dentin porcelain specimens were given different surface textures with modified surface roughnesses (Ra) and different levels of waviness (Wa). Measurements of transmittance, reflectance, and CIE L*a*b* values were made with a spectrocolorimeter (PR-650) after standard finishing of the enamel-dentin porcelain complex. Translucency parameters (TP) and color difference (ΔE) were calculated with CIE L*a*b* values, respectively. The data were statistically analyzed by 1-way ANOVA and Fisher's LSD (least significant difference) post hoc tests (α=.05). RESULTS: Transmittance, reflectance, and the translucency parameter were influenced significantly by surface roughness (P<.05) and waviness values (P<.01). With a decrease in the Ra value from 1.23 µm to 0.15 µm, mean reflectance values increased from 37.01% to 38.63%, while mean values of transmittance and the translucency parameter decreased from 1.04% to 0.87% and 19.44 to 18.03, respectively. With an increase of the Wa value from 0.0 mm to 0.2 mm, mean values of reflectance decreased from 37.06% to 30.30%, while transmittance and the translucency parameter increased from 1.10% to 2.05% and 19.15 to 20.01, respectively. Color difference values (ΔE) ranged from 0.30 to 1.45 (Ra group) and from 1.46 to 4.16 (Wa group), respectively. CONCLUSIONS: Surface texture of dentin porcelain significantly influenced the optical properties of enamel-dentin porcelain specimens, and surface waviness (Wa) had higher correlation coefficients with optical parameters than did roughness (Ra).

Clinical threshold of the translucency parameter of maxillary central incisors.

The aim of this in vivo study is to describe the clinical threshold and relative factors associated with the translucency of maxillary central incisors. Bilateral maxillary central incisors were measured in 106 individuals using a digital colorimeter against black and white backings. The translucency parameters (TP) of incisors and the difference in TP (ΔTP) between the left and right maxillary central incisors of the same individual was calculated. The mean TP value of the maxillary incisors was 8.22. There was a significant effect of age on the translucency of the maxillary central incisors (p<0.05). The TP of females was higher than that of males (p<0.05). The absolute mean value of ΔTP was 1.33. The ΔTP of the two maxillary central incisors in the same individual can be used as a reference for the threshold value of translucency.

Clinical characteristics of chronic hepatitis B cured by peginterferon in combination with nucleotide analogs.

OBJECTIVES: The purpose of this study was to analyze the clinical characteristics of chronic hepatitis B (CHB) cured by antiviral therapy. METHODS: Forty-two patients with CHB were enrolled. All patients had been treated with peginterferon (Peg-IFN) in combination with nucleoside analogue (NA) therapy for variable amounts of time, and all had been successfully cured of the disease. RESULTS: The combined treatment time for all participants was 124.7 ± 58.8 weeks, and the average Peg-IFN treatment time was 102.6 ± 56.1 weeks. At 24 weeks, Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) had decreased more than 50% from baseline. Multivariate logistic regression analysis of the week 96 HBsAg-clearing group and the non-HBsAg-clearing group showed a statistically significant difference in baseline HBV DNA levels and week 48 HBsAg levels. Those which baseline HBV DNA was < 2.75 log10 IU/mL, and week 48 HBsAg levels were < 0.88 log10 IU/mL were more likely to achieve rapid HBsAg clearance at 96 weeks. This suggests that low levels of baseline HBV DNA and week 48 HBsAg are a predictor of rapid HBsAg clearance at 96 weeks. CONCLUSIONS: Individualized extension of combination therapy to more than 96 weeks depending on the patient's response and adverse reaction conditions can help achieve a clinical cure. Patients with low baseline HBV DNA and low HBsAg levels at 48 weeks achieve HBsAg clearance more quickly than other populations.

The combination therapy of Peginterferonα and entecavir for HBeAg-positive chronic hepatitis B with high HCC risk.

The population of HBV infection with family history of hepatocellular carcinoma (HCC) is the high risk group for the development of HCC. The aim of this study was to evaluate the effect of the de novo combination therapy including pegylated-interferon α-2a (PEG-IFNα-2a) and entecavir (ETV) in this high risk population. The study recruited 58 Hepatitis B e Antigen (HBeAg)-Positive CHB patients patients with HBV-DNA > 107 IU/mL, genotype B or C and HCC family history and were treated for 48 weeks. Patients without HBeAg loss at the 48th week were 40 patients and extended the combination therapy to 96 weeks. All patients were followed up to 120 weeks. The rate of HBeAg loss and HBsAg loss was 12/40(30.0%) and 2/40(5.0%) at week 120 respectively. When logistic regression analysis was used to identify viables of HBeAg loss, HBV-DNA levels <20 IU/mL at week 48 was found to have a 6.02 fold increased probability (95% CI = 1.17-30.40, P = .03) of HBeAg loss. Patients with HBV-DNA levels <20 IU/mL at week 48 had a high probability of HBeAg loss 8/17(47.1%), HBsAg loss 2/17(11.8%), compared to 4/23(17.4%), 0/23(0%) in patients with HBV-DNA ≥ 20 IU/mL. Combination therapy for 96 weeks was well tolerated. During the combination therapy, low-level viremia during treatment is reversely associated with response. The combination therapy of PEG-IFNα and ETV was suggested to extend to 96 weeks when HBV-DNA was completed suppressed at week 48.

Clinical and economic impact of oxidized regenerated cellulose for surgeries in a Chinese tertiary care hospital.

Aim: To assess the impact of oxidized regenerated cellulose (ORC) on blood transfusion and hospital costs associated with surgeries. Patients & methods: This retrospective cohort study selected ten surgeries to create propensity-score matching groups to compare ORC versus nonORC (conventional hemostatic techniques such as manual pressure, ligature and electrocautery). Results: NonORC was associated with both higher blood transfusion volume and higher hospital costs than ORC in endoscopic transnasal sphenoidal surgery, nonskull base craniotomy, hepatectomy, cholangiotomy, gastrectomy and lumbar surgery. However, nonORC was associated with better outcomes than ORC in open colorectal surgery, mammectomy and hip arthroplasty surgery. Conclusion: When compared with conventional hemostatic technique, using ORC could impact blood transfusion and hospital costs differently by surgical settings.

Translucency of newly extracted maxillary central incisors at nine locations.

STATEMENT OF PROBLEM: In addition to color, translucency is one of the primary factors influencing the esthetics of a dental prosthesis. Due to difficulties in measuring the translucency of natural teeth, minimal data are available. PURPOSE: The purpose of this study was to measure the translucency of newly extracted maxillary central incisors and analyze the relationship between translucency, anatomic location, and age. MATERIAL AND METHODS: The translucency of 32 newly extracted maxillary central incisors was measured with a spectrocolorimeter (PR-650) at 9 locations on the tooth crown. These locations were identified by dividing the tooth incisally to cervically and medially to laterally in equal dimensions. The relationships between transmittance, locations, and age were analyzed by univariate analysis of variance (alpha=.05). RESULTS: The transmittance of maxillary central incisors ranged from 0.13% to 0.65%, which decreased from incisal to cervical (P<.05). Age also affected transmittance in certain locations of the crown; older teeth demonstrated higher transmittance (P<.05). CONCLUSIONS: Transmittance of the maxillary central incisor was variable at different locations of the crown and was positively correlated with age.

[Effect of erosion on strength of dental infiltrated Al2O3 ceramics].

The objective of the research is to investigate the elements of routine sandblast technique on the evolution of bending strength of dental infiltrated Al2O3 ceramics and the underlying erosion mechanism. The plane specimens of an infiltrated ceramic were manufactured, polished and then tested under the modified pen-like sandblasting apparatus (90 degrees erosive angle and 10 mm sandblasting distance), with different grit sizes, working pressure and disposing time. Half of samples were selected randomly and sintered subsequently with Vitadur alpha veneering porcelain. Before and after sintering, the three-point-bending strengths was measured, and the surfaces of dental porcelain were observed with SEM and LCSM. The bending strength of ceramics decreased significantly after sandblast as compared with that of empty control group. After the procedure of sintering the veneering porcelain, the descending evolution of bending strength slowed down. Under the present manufacturing conditions, grit size effect is prominent among those correlative elements of sand grit size, working pressure and disposing time. And fatigue cracking characterizes the mechanism of erosion of dental infiltrated Al2O3 ceramics.

[Influence of different surface roughness of opaque porcelain on reflectance and L* value of porcelain fused to metal].

OBJECTIVE: The purpose of this study was to investigate how different surface roughness of opaque porcelain influence reflectance and CIE L* value of porcelain fused to metal (PFM) restorations. METHODS: 48 casted Ni-Cr alloy metal specimens (12.0 mm x 1.0 mm) were fabricated with ShoFu Vintage Halo porcelain and divided into six groups, eight pieces for each group. The specimens in the first group without polishing were used as control. Other groups were polished against 200-, 400-, 600-, 800-, and 1000-grit sandpaper after sintered, respectively. Surface roughness and color parameters of the specimens were measured with a Surface Roughometer EX2154-13 and a spectrocolorimeter, respectively. Ra (arithmetical mean deviation of the profile) was the main standard value to describe the surface roughness of many kinds of meatal or porcelain materials, and here we used it to express surface roughness of opaque porcelain. The data were statistically analyzed by one-way analysis of variance (alpha = 0.05) in SPSS 13.0. RESULTS: The reflectance value increased from 72.386 +/- 3.953 to 78.671 +/- 3.408, and CIE L* value from 90.189 +/- 1.200 to 93.496 +/- 1.070 with the increasing of surface roughness (Ra) of opaque porcelain from (0.226 +/- 0.069) microm to (0.706 +/- 0.082) microm. The same magnitude were also observed after body porcelain and enamel porcelain were sintered on with reflectance increased from 76.301 +/- 3.097 to 81.529 +/- 4.028, and CIE L* value from 80.694 +/- 1.564 to 84.604 +/- 2.964. CONCLUSION: The surface roughness of opaque porcelain had effects on the reflectance and value of PFM restorations. Within the limitation of this study, the recommended Ra range of opaque porcelain was 0.23-0.50 microm.

[Influence of manufacture technique on translucency and color of dental porcelain].

OBJECTIVE: To study the influence of manufacture technique on the translucency and color of dental porcelain. METHODS: Specimens were made of VITA VMK 95 dentin porcelain and enamel porcelain and divided into 3 groups: Sintering times group (1, 2, 4, 6, 8 and 10 times), sintering temperature group (910, 920, 930, 940 and 950 degrees C), sintering vacuum group (95, 65, 35 and 0 kPa). Transmittance, Y, dominant wavelength and saturation were measured by PR-650 spectra scan spectrocolorimeter. RESULTS: Transmittance of dentin porcelain increased after 6 times repeated sintering. Transmittance of enamel porcelain increased first after the second sintering, and then became decreasing when sintering more than 2 times. Transmittance of enamel porcelain deceased when sintering temperature was lower than standard. Decrease of sintering vacuum caused the transmittance of dentin and enamel porcelain decreased. The changing of value was coordinated with transmittance. Dominant wavelength and saturation had negative correlation with sintering times and temperature, and positive correlation with vacuum. CONCLUSION: Sintering times, temperature and vacuum all had prominent effects on the translucency and color of dental porcelain. Comparing with dentin porcelain, enamel porcelain was more sensitive with the modification of manufacture technique.

[Comparison of translucency between enamel, dentin and Vita veneer porcelain].

PURPOSE: To compare the translucency between enamel, dentin and dental porcelain. METHODS: 32 newly extracted vital human central incisors were collected and cut into 0.8mm enamel slices and 1.0 mm dentin slices. 1.0 mm dental porcelain specimen were made with different Vita veneer porcelain, EN1, EN2, T4, Window, A1, A2, A3, A3.5, A4, B2, C2, D2, 3 samples for each kind. The transmittance and reflectance of tooth slices and porcelain specimen were measured by PR-650 spectra scan spectrocolorimeter. The transmittance coefficients were also calculated. The 95% confidence interval was obtained by SPSS 12.0 software package. SNK method was used to compare the transmittance coefficients of different dentin porcelains. RESULTS: The transmittance coefficient of tooth enamel ranged from 0.0817 mm(-1) to 0.1009 mm(-1), which was higher than that of two kinds of enamel porcelain (0.0507 mm(-1) for EN1 and 0.0408 mm(-1) for EN2). The transmittance coefficient of dentin (0.0418-0.0482 mm(-1)) was also higher than that of dentin porcelain (0.016-0.027 mm(-1)). The transmittance coefficient of dentin porcelain decreased with the increasing of chroma (P<0.05). CONCLUSIONS: Prominent difference exists between translucency of tooth tissue and dental porcelain, especially between enamel and enamel porcelain.