[Analysis of lung cancer screening through low-dose spiral computed tomography among petroleum company staffs in Sichuan-Chongqing Area in 2020].

Objective: To provide scientific evidence for early lung cancer screening, to analyze the incidence of pulmonary nodules among petroleum company staffs in Sichuan-Chongqing Area. Methods: In January 2021 , 6002 petroleum company staffs in Sichuan-Chongqing Area which scanned by low-dose spiral computed tomography (LDCT) of chest in medical examination center in 2020 were retrospectively collected as objects. Their imaging and clinical data were collected. χ(2) test was used to analyze the differences in the detection rates of lung nodules and suspected lung cancer nodules among workers in petroleum company staffs of different genders, ages and types of work. Results: Among the 6002 objects, 3853 (64.2%) were male and 2149 (35.8%) were female, with an average age of (47.25±12.13) years old. A total of 431 cases (7.2%) of pulmonary nodules and 57 cases (0.9%) of suspected lung cancer nodules were detected. 45 cases were followed up with surgical treatment, and 41 cases (91.1%) of lung cancer were diagnosed by postoperative pathology. There were significant differences in the detection rates of pulmonary nodules and suspected lung cancer nodules between different age groups (χ(2)=51.23, 18.81 , P<0.001). The detection rates of pulmonary nodules in the age groups 51-60 years old and ≥61 years old were higher than those in the age groups≤40 years old and 41-50 years old (P<0.05). The detection rate of suspected lung cancer nodules in the age group≥ 61 years old was higher than those in the age groups≤40 years old, 41-50 years old and 51-60 years old (P< 0.05) . And the detection rate of suspected lung cancer pulmonary nodules in oil workers was higher than that of ordinary workers (P<0.05) . Among female objects, the detection rate of pulmonary nodules in oil workers was higher than that in ordinary workers (χ(2)=8.09, P=0.004) . The detection rate of pulmonary nodules in oil workers aged ≥61 years old was higher than ordinary workers (χ(2)=37.94, P<0.001) . Among male objects, the detection rate of suspected lung cancer pulmonary nodules in oil workers was higher than that in ordinary workers (χ(2)=8.42, P=0.004) . The detection rates of suspected lung cancer pulmonary nodules in oil workers aged 51-60 years old and ≥61 years old groups were higher than those of ordinary workers (χ(2)=4.70, 8.74; P=0.030, 0.003) . Conclusion: LDCT is suitable for early lung cancer screening for petroleum company staffs. During the clinical screening process, LDCT should be used as a routine physical examination item for petroleum workers older than 51 years old.

[Low-levels of HBsAg quantification at 48-week in HBeAg-negative chronic hepatitis B patients are the advantageous population for HBsAg clearance].

Objective: To analyze the therapeutic effect on HBeAg-negative chronic hepatitis B patients treated with Peg-IFNα-2a combined with NAs to obtain the influencing factors for predicting HBsAg clearance. Methods: A retrospective study was conducted to investigate the effect of pegylated interferon alpha-2a combined with nucleoside analogues (lamivudine/adefovir dipivoxil) on HBeAg-negative chronic hepatitis B. The treatment course was 96 weeks. Patients were followed up 120 weeks after the treatment. HBsAg clearance at 120 weeks was taken as the objective of the study. Logistic regression and receiver operating characteristic curve analysis screened the related factors affecting HBsAg clearance. χ (2) test was used to compare count data. Results: 111 patients were treated with pegylated interferon alpha-2a combined with nucleoside analogues, and 107 patients completed the scheduled course of treatment and follow-up. HBsAg clearance rate at120 week was 29.0% (31/107). The influencing factors for analysis were: (1) gender had no effect on HBsAg clearance rate; age and baseline levels of HBV DNA and alanine aminotransferase had no significant effect on HBsAg clearance; low baseline level of HBsAg (< 3.023 lgIU/ml) was beneficial to HBsAg clearance. The area under the working characteristic curve of the subjects was 0.746, the positive predictive value was 44.4%, and the negative predictive value was 86.8%. (2) HBsAg quantification or decline in 24 weeks and 48 weeks of treatment had a good predictive effect on HBsAg clearance, and the 48 weeks predicted value was higher than 24 weeks. When the HBsAg quantification was≤2.070 lgIU/ml at 48 weeks, the area under the receiver operating characteristic curve was 0.931, the positive predictive value was 52.8%, and the negative predictive value was 94.4%. When HBsAg decreased from baseline to≥0.991 lgIU/ml, the area under the receiver operating characteristic curve was 0.888, the positive predictive value was 50.8%, and the negative predictive value was 97.9%. (3) The analysis of HBsAg subgroup levels at 48 weeks suggested that the "interval analysis" can forecast HBsAg clearance more exactly than "nodal analysis" .The final HBsAg clearance rate of 100 IU/ml < HBsAg≤1 000 IU/ml, 10 IU/ml < HBsAg≤100 IU/ml and HBsAg≤10 IU/ml groups reached 6.7%, 31.8% and 67.7%, respectively. (4) The ALT abnormal group in the course of treatment obtained a higher HBsAg clearance rate (48.0%, 12/25). Conclusion: 96-weeks long-term treatment with pegylated interferon-alpha -alpha-2a combined with nucleoside analogues for HBeAg-negative chronic hepatitis B has a good predictive value for HBsAg clearance at baseline and during treatment. The "interval level" of HBsAg at 48-weeks is more accurate in predicting HBsAg clearance, suggesting that HBeAg-negative chronic hepatitis B patients with low HBsAg levels at 48-weeks are the advantageous populations with HBsAg clearance. These patients are worthy of prolonged treatment to pursue "clinical cure".

[Impaired hypoxic ventilatory response and related factors in Han and Uygur patients with obstructive sleep apnea-hypopnea syndrome].

Objective: To investigate the respiratory central hypoxia response and its related factors in Han and Uygur patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: One hundred and sixty six OSAHS patients were selected from Jan. 2016 to Dec. 2016 in Department of Respiratory and Critical Care Medicine, Kelamayi Central Hospital, including 69 cases of Han nationality and 97 cases of Uygur nationality. Seventy-three healthy subjects of Uygur nationality were enrolled as the control group. All of them under went sleep monitoring, nocturnal oxygen saturation (SaO(2)), pulmonary function and respiratory central hypoxia response. Results: The 3 groups were matched for age, gender, body mass index(BMI) and apnea-hypopnea index(AHI). The Uygur patients had a higher oxygen desaturation index (ODI4) [(30±22) per hour vs (18±17) per hour ] than Han patients of the same age and BMI. Compared to Han patients, Uygur patients had weaker hypoxic responsiveness [(-0.41±0.23) L·min(-1)·%(-1) vs (-0.36±0.22) L·min(-1)·%(-1,) P<0.05], and the difference still existed after adjusting for AHI [(-0.31±0.21) L·min(-1)·%(-1) vs (-0.41±0.22) L·min(-1)·%(-1,) P<0.05] in mild OSAHS, but this difference was not significant in severe OSAHS. Conclusions: The central hypoxic response in Uygur OSAHS patients was lower than that in Han OSAHS patients and normal controls.

[Daytime hypercapnia in patients with obstructive sleep apnea hypopnea syndrome in Han and Uygur nationality].

Objective: To evaluate the incidence and factors related to daytime hypercapnia in Han and Uygur patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: There were 221 patients with OSAHS (include 179 Han patients and 42 Uygur patients) in Sleep Center of Department of Respiratory and Critical Care Medicine of Karamay Central Hospital from 2015, Jan to Dec. All the patients underwent polysomnography (PSG), nocturnal oximetry, daytime blood gas analysis, pulmonary function test and Mouth occlusion pressure (P0.1) results were recorded. The features of hypercapnia was analyzed for patients with OSAHS, and linear regression analysis was used to evaluate the arterial carbon dioxide partial pressure (PaCO2) levels and related factors. Results: Daytime hypercapnia occurred in 16.7% (37/221) of the 221 patients with OSAHS. Compare with no hypercapnia groups, the body mass [(31.6±5.6) vs (27.9±1.7) kg/m2], sleep apnea index (AHI) [(40.9±26.3) vs (32.2±20.1) times/h], the percentage of time spent at oxygen saturation below 90 (SIT90) [(38.6±31.9)% vs (23.9±23.6)%], P0.1 [(3.08±2.86) vs (2.03±1.20) mmHg, 1 mmHg=0.133 kPa] were higher in hypercapnia groups, but the mean nocturnal arterial oxygen saturation (MSaO2) [(86.0±15.5)% vs (92.0±3.0)%], the nadir arterial oxygen saturation (LSaO2) [(68.9±13.0)% vs (75.3±9.9)%] and arterial partial pressure of oxygen (PaO2) [(74.5±23.0) vs (86.1±14.8) were lower in hypercapnia groups (all P<0.05). Compare with Han patients with OSAHS, MSaO2 and LSaO2 was lower, PaCO2 and P0.1 was higher in Uygur patients (all P<0.05). Conclusions: Uygur OSAHS patients with hypercapnia have a higher daytime PaCO2 than the Han counterparts. BMI, AHI, MSaO2, P0.1 level are all related with daytime hypercapnia in OSAHS.

Non-invasive foetal RHD genotyping via real-time PCR of foetal DNA from Chinese RhD-negative maternal plasma.

BACKGROUND: A majority of studies predicting the foetal RhD blood group in free foetal DNA from RhD-negative maternal plasma have been conducted in Caucasian populations, whereas limited data have been accumulated for Asian populations. In this study, we assessed the feasibility of prenatal genotyping of RHD in RhD-negative Chinese pregnant women. MATERIALS AND METHODS: Cell-free plasma DNA was extracted from 78 RhD-negative Chinese women carrying a singleton foetus (gestation between 14 and 40 weeks). Foetal DNA was confirmed by testing SRY or nine different polymorphic STR loci in the maternal plasma and buffy coat. Foetal RHD exons 5, 7 and 10 and intron 4 were successfully amplified with RQ-PCR. The RHD1227A allele was examined in all RhD-positive individuals. The foetal RHD genotyping results were compared with the infant cord blood serological analysis. RESULTS: Among the 78 specimens, RHD genotyping results of 70 cases were in complete concordance with serological results from foetal umbilical cord blood. Sixty of these cases were identified as RhD-positive, and 10 cases were typed as RhD-negative. In addition, five cases were 'false-positives', while three cases were considered inconclusive. The detection rate was 89.7% (70/78). In four of the five 'false-positive' cases, the RhDel phenotype was assessed by detecting the RHD1227A allele. Thus, this method yielded a 94.9% (74/78) accuracy rate. CONCLUSIONS: The correct foetal RhD phenotype may be accurately predicted from RhD-negative maternal plasma in Chinese subjects. The RHD1227A allele proved to be an important genetic marker in the RhDel Chinese population.

Pepsin-induced changes in the size and molecular weight distribution of bovine casein during enzymatic hydrolysis.

Bovine casein was digested with pepsin at pH 2.0 in a batch-stirred tank reactor. To investigate the effect of peptic digestion on the aggregate size and molecular weight distribution of bovine casein, the resulting hydrolysates were examined by size-exclusion chromatography coupled with multiangle laser light scattering and dynamic light scattering. Casein was resolved by size-exclusion chromatography into 2 major peaks corresponding to aggregates and monomers, both of which showed a continuous decrease as hydrolysis proceeded. However, the ratio of aggregates to monomers was maintained at almost 1 (2:2.5) during the initial 30-min hydrolysis, indicating that the caseins in solution were in a type of equilibrium between aggregates and monomers. Upon peptic hydrolysis, casein aggregates increased in size and molecular weight, and exhibited a decrease in intermolecular repulsion. This finding was confirmed by dynamic light scattering measurements, which traced the changes in the hydrodynamic radii and light scattering intensities of casein hydrolysates. In addition, the release kinetics of peptide fractions with different molecular weights was also examined. It was concluded that the increase in hydrophobic attraction and the reduction in intermicellar repulsion might promote the growth in aggregate size of bovine casein during the limited hydrolysis.

[Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study].

Objective: To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment. Methods: Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed. Results: The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) . Conclusions: Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

Tumorigenic activity of the 4,5- and 9,10-dihydrodiols of benzo[j]fluoranthene and their syn- and anti-diol epoxides in newborn mice.

Benzo[j]fluoranthene (B[j]F), trans-4,5-dihydro-4,5-dihydroxy-B[j]F, and trans-9,10-dihydro-9,10-dihydroxy-B[j]F were evaluated for tumorigenic activity in newborn CD1 mice. These dihydrodiols were assayed at doses of 1.10 and 0.275 mumol/mouse. B[j]F and the syn- and anti-diol epoxides derived from these dihydrodiols were evaluated at doses of 1.10, 0.275, and 0.110 mumol/mouse (80 mice/group). trans-4,5-Dihydro-4,5-dihydroxy-B[j]F was more potent than trans-9,10-dihydro-9,10-dihydroxy-B-[j]F in inducing pulmonary tumors in both female and male mice. Administration of 1.10 mumol of trans-4,5-dihydro-4,5-dihydroxy-B[j]F resulted in a 90-92% incidence of pulmonary tumors with an average of 3.6 and 4.2 tumors/mouse among female and male mice, respectively. A similar tumorigenic activity was observed for B[j]F in lung. trans-9,10-Dihydro-9,10-dihydroxy-B[j]F was significantly less tumorigenic (P < 0.05), producing a 44 and 64% incidence of pulmonary tumors at a dose of 1.10 mumol with an average of 0.8 and 1.0 tumor/mouse in female and male mice, respectively. A statistically significant (P < 0.001) incidence of hepatic tumors was also produced among male mice administered either B[j]F, trans-4,5-dihydro-4,5-dihydroxy-B[j]F, or trans-9,10-dihydro-9,10-dihydroxy-B[j]F at a dose of 1.10 mumol/mouse. In comparing the tumorigenicity of the diasteromeric diol epoxides derived from both trans-4,5-dihydro-4,5-dihydroxy-B[j]F and trans-9,10-dihydro-9,10-dihydroxy-B[j]F, the anti-diasteromers exhibited greater tumorigenic activity. The most tumorigenic diol epoxide was anti-4,5-dihydroxy-6,6a-epoxy-4,5,6,6a-tetrahydro-B[j]F. At a dose of 0.275 mumol, this diol epoxide induced a 96 and 100% incidence of pulmonary tumors in female and male mice, with an average of 8.6 and 5.0 tumors/mouse, respectively. anti-9,10-Dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-B[j]F at this dose produced a 56 and 95% incidence of pulmonary tumors in female and male mice with an average of 1.0 and 2.8 tumors/mouse, respectively. syn-4,5-Dihydroxy-6,6a-epoxy-4,5,6,6a-tetrahydro-B[j]F and syn-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-B[j]F at a dose of 0.275 mumol did not induce a significant incidence (P > 0.05) of pulmonary tumors in female or male mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Discordant HIF1A mRNA levels and oxidative stress in placental shares of monochorionic twins with selective intra-uterine growth restriction.

INTRODUCTION: Oxidative stress is a key factor in the pathogenesis of intra-uterine growth restriction in singleton. However, its role in selective intra-uterine growth restriction (sIUGR) in monochorionic twins (MCT) is still unknown. This study explored the characteristics of oxidative stresses in the placenta shares of MCT and analyzed their possible connections with sIUGR. METHODS: The placental levels of hypoxia inducible factor-1α gene (HIF1A)mRNA, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) were evaluated in normal MCT (Group A) and sIUGR MCT (Group B). The results were compared between the placental shares of the larger twins (A1/B1) and smaller twins (A2/B2). RESULTS: Placental HIF1A mRNA level significantly increased in Group B. Particularly, HIF1A mRNA level was elevated in the placenta share of the growth-restricted fetus (B2) than the co-twin (B1) (P = 0.036). More discordant HIF1A mRNA level was detected in Group B than Group A with larger inter-twin difference (P = 0.021). The levels of MDA and 8-OHdG were significantly higher in B2 than B1 in sIUGR MCT (P < 0.05). Both the inter-twin differences of MDA and 8-OHdG were also significantly larger in Group B (P < 0.05), indicating that discordant oxidative stress existed in the placental shares of sIUGR pregnancies. Finally, MDA concentration was found inversely correlated with neonatal birth weight, in both sIUGR (r = -0.650, P = 0.022) and normal MCT (r = -0.632, P = 0.027) pregnancies. DISCUSSION: The elevation of HIF1A mRNA, and MDA/8-OHdG levels in placenta shares of sIUGR MCT suggests that oxidative stress may be involved in the pathogenesis of sIUGR.

Exceptional tumor-initiating activity of 4-fluorobenzo[j]-fluoranthene on mouse skin: comparison with benzo[j]-fluoranthene, 10-fluoro-benzo[j]fluoranthene, benzo[a]pyrene, dibenzo[a,l]pyrene and 7,12-dimethylbenz[a]anthracene.

Exceptional tumorigenic potency was observed with 4-fluorobenzo[j]fuoranthene (4-fluoroB[j]F) relative to benzo[j]fluoranthene (B[j]F) and 10-fluorobenzo[j]fluoranthene (10-fluoroB[j]F) in a mouse skin initiation promotion bioassay. Comparison of the tumorigenic response obtained at total initiating doses of 50, 100, and 1000 nmol firmly established the greater tumorigenic potency of 4-fluoroB[j]F. B[j]F produced a significant tumorigenic response only at total initiating doses of 100 and 1000 nmol per mouse. 10-FluoroB[j]F produced a significant tumorigenic response only at the highest initiating dose, 1000 nmol per mouse. In contrast, 4-fluoroB[j]F produced a significant tumorigenic response at all three doses. At a total initiating dose of 50 nmol, a 90% incidence of tumor-bearing mice with an average of 3.05 tumors per mouse was observed with 4-fluoroB[j]F. A second initiation promotion bioassay was performed to establish the tumorigenic potency of 4-fluoroB[j]F relative to benzo[a]-pyrene (B[a]P), 7,12-dimethylbenz[a]anthracene (DMBA), and dibenzo[a,l]pyrene (DB[a,l]P). 4-FluoroB[j]F did exhibit significant tumor-initiating activity at doses of 10 and 25 nmol per mouse, inducing a 45 and 60% incidence of tumor-bearing mice with an average of 0.75 and 1.65 tumors per mouse, respectively. While B[a]P was not tumorigenic at these doses, DMBA and DB[a,l]P exhibited significant tumorigenic activity at doses of 1, 4, 10, and 25 nmol per mouse. DB[a,l]P induced a 95% incidence of tumor-bearing mice with an average of 5.0 tumors per mouse at a total initiator dose of 1 nmol. DMBA at this dose produced an 85% incidence of tumor-bearing mice with an average of 1.30 tumors per mouse. The results of these initiation promotion bioassays clearly demonstrate that 4-fluoroB[j]F is significantly more active than B[j]F, 10-fluoroB[j]F and B[a]P and less active than either DMBA or DB[a,l]P as a tumor initiator on mouse skin.

Mutagenic activity of the 4,5- and 9,10-dihydrodiols of benzo[j]fluoranthene and their syn- and anti-dihydrodiol epoxides in Salmonella typhimurium.

The objective of this study was to determine the relative mutagenic activities of the major dihydrodiol metabolites of benzo[j]fluoranthene (B[j]F) and their corresponding syn- and anti-dihydrodiol epoxides. Salmonella typhimurium tester strains TA97a, TA98, and TA100 were used to evaluate the mutagenic potencies of the parent hydrocarbon and these suspect proximate and ultimate mutagenic metabolites. B[j]F and the trans-dihydrodiol metabolites were active only in the presence of an external metabolic activation system (S9) with the exception of the B[j]F-4,5-diol, which was weakly active in TA98 and TA100 in the absence of S9. The B[j]F-4,5-diol was more mutagenic than the B[j]F-9,10-diol in tester strains TA98 and TA100, whereas the opposite effect was observed in TA97a. In the absence of S9, the anti-B[j]F-4,5-diol epoxide was more mutagenic than the syn-B[j]F-4,5-diol epoxide and the syn- and anti-B[j]F-9,10-diol epoxides in tester strains TA97a and TA100. The exceptional mutagenic potency of the anti-B[j]F-4,5-diol epoxide in TA100 resembles that observed by epoxides located within a fjord, or by the anti-diol epoxides of bay region methylated polycyclic aromatic hydrocarbons. In contrast, the mutagenicity of the pseudo bay region dihydrodiol epoxides arising from the B[j]F-9,10-diol more closely resembles that observed with the classical bay region dihydrodiol epoxides of chrysene. In summary, both dihydrodiol metabolites of B[j]F are mutagenic in S. typhimurium, and the relative potency varies among the tester strains. The highest mutagenic response was achieved in tester strain TA100, which detects base-pair substitutions. The most potent direct-acting dihydrodiol epoxide in this tester strain was the anti-B[j]F-4,5-diol epoxide, which agrees with the results of mouse skin painting studies that indicate that the B[j]F-4,5-diol is more tumorigenic that the parent hydrocarbon or the B[j]F-9,10-diol. A covalent DNA adduct formed between the anti-B[j]F-4,5-diol epoxide and deoxyguanosine was the major species of DNA adduct formed in S. typhimurium. This adduct corresponds to the major DNA adduct formed in mouse skin following application B[j]F.

Effect of fluorine substitution on benzo[j]fluoranthene genotoxicity.

The metabolism and mutagenic activity of 4-fluorobenzo[j]fluoranthene (4F-B[j]F) and 10-fluorobenzo[j]fluoranthene (10F-B[j]F) were evaluated and compared with benzo[j]fluoranthene (B[j]F) using an identical rat liver homogenate preparation. Previous studies have shown that the major genotoxic metabolites of B[j]F are the 4,5- and 9,10-dihydrodiol. The 9,10-dihydrodiol was the principal metabolite formed in the case of 4F-B[j]F, while the 4,5-dihydrodiol was the principal metabolite formed in the metabolism of 10F-B[j]F. Studies on the relative genotoxicity of these fluorinated derivatives were performed to indirectly determine the possible contribution of the 4,5- and 9,10-dihydrodiol in the activation of B[j]F to a genotoxic agent. In the presence of microsomal activation, both of these fluorinated derivatives of B[j]F were more mutagenic in S. typhimurium TA97a, TA98 and TA100 than B[j]F. However, differences in mutagenic potency were observed between 4F- and 10F-B[j]F. 10F-B[j]F had similar mutagenic potency to 4F-B[j]F in TA97a and TA98 at doses associated with the linear portion of the dose response curve. However, a slightly higher mutagenic response was observed with 10F-B[j]F in TA98 at doses above 5 nmol. In contrast, 4F-B[j]F was more active than 10F-B[j]F as a mutagen in TA100. The tumor-initiating activity of these analogs on mouse skin was assessed at doses of 2.0, 1.0 and 0.3 mumol. Skin irritation was observed with the fluorinated B[j]F derivatives at doses above 0.3 mumol. At a dose of 0.3 mumol, 4F-B[j]F exhibited tumorigenic activity which was similar to B[j]F. In contrast, 10F-B[j]F was less active than B[j]F at all three doses assayed. Both fluorinated derivatives of B[j]F formed higher levels of DNA adducts in vivo in mouse skin than B[j]F. A modified 32P-postlabeling method was required to detect fast migrating B[j]F:DNA adducts that went undetected in previous studies. The level of DNA adducts formed from 4F-B[j]F was considerably greater than the levels observed with 10F-B[j]F. This is consistent with the greater mutagenic activity in S. typhimurium TA100 and tumor-initiating activity exhibited by 4F-B[j]F. These studies suggest that fluorine substitution may significantly alter the intrinsic genotoxicity of the 4,5- and 9,10-dihydrodiol of B[j]F. These data also imply that B[j]F may be primarily activated via the formation of the 9,10-dihydrodiol metabolite. This pathway of activation is inconsistent with our previous studies which indicate that the 4,5-dihydrodiol is the most important pathway of activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in graves' ophthalmopathy after radioiodine and anti-thyroid drug treatment of Graves' disease from 2 prospective, randomized, open-label, blinded end point studies.

AIMS: A significant association between radioiodine therapy (RIT) and the development or the worsening of pre-existing Graves' ophthalmopathy (GO) has been reported. This post-hoc analysis of 2 studies attempted to describe the changes observed in pre-existing or new-onset GO following RIT with the goal of euthyroidism rather than hypothyroidism and to describe the relationship GO changes and the final outcome. PATIENTS AND METHODS: In 2 prospective, randomized open-label blinded endpoint trials, patients received radioiodine alone; or, patients received radioiodine or antithyroid drug therapy (ATD). The severity and activity of GO were assessed during a 9-12-year follow-up. The study end points in study 1 were euthyroidism, hyperthyroidism, hypothyroidism, and changes in GO. In study 2, the end points were euthyroidism, hyperthyroidism, hypothyroidism, relapse, and changes in GO. RESULTS: Both RIT and ATD were associated with worsening GO and new-onset GO. Both RIT and ATD led to similar aggravation of pre-existing GO or the development to new-onset GO. After RIT or ATD, the euthyroid patients (without levothyroxine substitution) demonstrated an improvement in GO, with 78-89% patients with preexisting GO exhibiting improvement, whereas hyperthyroid, hypothyroid and relapsed patients had worsening or new-onset GO. CONCLUSIONS: Thyroid function is a dominant risk factor. Thyroid function may be the most important determinant in worsening or new-onset GO in both the natural disease course and in treated patients, independent of the kind of treatment. Therefore, we recommend euthyroidism as a goal of treatment.

Placental expression of osteopontin(OPN) in monochorionic twins with discordant growth.

Shallow invasion could result in pathological processes of placenta leading to fetal growth restriction (FGR) in singletons and twins. Osteopontin (OPN) plays an important role in trophoblast invasion. So our study aims to investigate the expression level of OPN in placenta of discordant monochorionic (MC) twins. OPN expression was compared in the placental samples of 10 discordant MC twins and 12 concordant MC twins. OPN levels were evaluated using quantitative Real-time PCR and western blot. Our results showed that OPN expression at mRNA and protein level was significantly decreased in placenta (p < 0.05) of small fetuses in discordant MC twins. The expression level of OPN transcript strongly correlated with the territory of placenta.

Fabrication and Evaluation of Curcumin-loaded Nanoparticles Based on Solid Lipid as a New Type of Colloidal Drug Delivery System.

Curcumin has very broad spectrum of biological activities; however, photodegradation, short half-life and low bioavailability have limited its clinical application. Curcumin-loaded solid lipid nanoparticles were studied to overcome these problems. The aim of this study was to optimize the best formulation on curcumin-loaded solid lipid nanoparticles. Emulsion-evaporation and low temperature-solidification technique was applied with monostearin as lipid carriers. The single factor analysis and orthogonal design were used to optimize formulation and various parameters were investigate. By the optimisation of a single factor analysis and orthogonal test, the particles size, polydispersity index, zeta potential, encapsulation efficiency and drug loading capacity of the optimised formulation were 99.99 nm, 0.158, -19.9 mV, 97.86%, and 4.35%, respectively. The differential scanning calorimetry and X-ray diffraction analysis results demonstrated new structure was formed in nanoparticles. The release kinetics in vitro demonstrated curcumin-loaded solid lipid nanoparticles can control drug release. These studies confirmed that curcumin-loaded solid lipid nanoparticles could be prepared successfully with high drug entrapment efficiency and loading capacity. Curcumin-loaded solid lipid nanoparticles may be a promising drug delivery system to control drug release and improve bioavailability.

Mental health status and factors that influence the course of Graves' disease and antithyroid treatments.

AIMS: Biological, psychological and social factors may interact with the mental health status of Graves' disease (GD) patients before and after antithyroid drug (ATD) treatment. Our aim was to quantify the impact of supportive and risk factors after recovery from GD which may enhance cure rates. PATIENTS AND METHODS: 300 patients were recruited for a 6-year prospective cohort study. Before and after treatment, we assessed the impact of biopsychosocial factors on the success of ATD treatment and mental health using the Symptom Checklist 90, the Eysenck Personality Questionnaire, the Life Event Scale, Simplified Coping Styles and the Perceived Social Support Scale. The patients routinely received ATD at least over 18 months. End-point was defined as cured (at least 2 years without a relapse after the withdrawal of ATD), otherwise as not cured. RESULTS: Regression analysis explained 80.5% of the influences affecting mental health. The odds ratios (OR) revealed positive coping styles (OR: 2.90, 95% CI, 1.09-7.68), negative events (OR: 1.04, 95% CI, 1.01-1.07) and social support (OR: 5.10, 95% CI, 2.77-9.40) as protective factors, predicting a cure for GD patients. These variables explained 61.7% of the influences leading to a cure or no cure. Large thyroid volume was a risk factor, predicting failure (OR: 0.865, 95% CI, 0.83-0.90, P<0.000). CONCLUSIONS: Enhancing positive coping strategies and social support is important to improve mental health in GD patients, to avoid compromising work-related performance and endangering a patient's social status.