Efficient macrocyclization facilitated by skeleton preorganization.

Reported here is the efficient macrocyclization facilitated by skeleton preorganization. A pyridylcarbazole macrocycle and a phenylpyridylcarbazole macrocycle was synthesized in yield up to 75%. Single-crystal structures and theoretic computation uncovered that the skeleton preorganization promoted the formation of cyclization-favorable conformation of noncyclic precursors via π⋯π interactions. This result provided a new approach for the efficient syntheses of macrocycles.

Sofosbuvir-based therapy for late pregnant women and infants with severe chronic hepatitis C: A case series study.

Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.

Tenofovir Alafenamide for Pregnant Chinese Women With Active Chronic Hepatitis B: A Multicenter Prospective Study.

BACKGROUND & AIMS: Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. METHODS: Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. RESULTS: One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. CONCLUSIONS: TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.

Restless legs syndrome in maintenance hemodialysis patients: an epidemiologic survey in Hefei.

OBJECTIVE: To investigate the prevalence of restless legs syndrome (RLS) in maintenance hemodialysis (MHD) patients and its possible influencing factors. METHODS: MHD patients were consecutively enrolled from five hemodialysis centers in Hefei. Clinical, demographics, and laboratory data were recorded from December 2013 to March 2014. RLS diagnosis scale, Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and kidney disease and quality of life (KDQOLTM-36) were used for analysis. RESULTS: A total of 269 MHD patients (81 women, 188 men) were enrolled, among which 39 patients were diagnosed as RLS. The median duration of dialysis therapy was 33 months and the prevalence of RLS was 14.5%. Compared with RLS-negative patients, RLS-positive patients had lower hemoglobin level (98.67 ± 13.50 vs 106.34 ± 17.75, P = 0.011) and higher alkaline phosphatase concentration [131.0 (98.0, 226.0) vs 94.0 (69.8, 157.5), P = 0.001]. The multivariate logistic regression showed that high hemoglobin level (OR 0.975, 95% CI 0.956-0.995, P = 0.015) was a protective factor for RLS, while high alkaline phosphatase (OR 1.003, 95% CI 1.001-1.005, P = 0.018) was an independent risk factor for RLS. RLS patients had significantly higher PSQI scores (P < 0.001), reduced subjective sleep quality (P < 0.001), increased sleep latency (P < 0.007), shorter sleep duration (P < 0.001), lower sleep efficiency (P = 0.001), higher sleep disturbances (P < 0.001), and increased daytime dysfunction (P = 0.019). CONCLUSION: Our findings demonstrated that the prevalence of RLS was 14.5% in Hefei. High hemoglobin level was a protective factor for RLS, and high alkaline phosphatase was an independent risk factor. RLS affects many aspects of quality of life and sleep quality, which may contribute to the presence of depression and anxiety.

One-step fabrication of biocompatible chitosan-coated ZnS and ZnS:Mn2+ quantum dots via a γ-radiation route.

Biocompatible chitosan-coated ZnS quantum dots [CS-ZnS QDs] and chitosan-coated ZnS:Mn2+ quantum dots [CS-ZnS:Mn2+ QDs] were successfully fabricated via a convenient one-step γ-radiation route. The as-obtained QDs were around 5 nm in diameter with excellent water-solubility. These QDs emitting strong visible blue or orange light under UV excitation were successfully used as labels for PANC-1 cells. The cell experiments revealed that CS-ZnS and CS-ZnS:Mn2+ QDs showed low cytotoxicity and good biocompatibility, which offered possibilities for further biomedical applications. Moreover, this convenient synthesis strategy could be extended to fabricate other nanoparticles coated with chitosan.PACS: 81.07.Ta; 78.67.Hc; 82.35.Np; 87.85.Rs.

Changes of Serum Trace Elements, AFP, CEA, SF, T3, T4 and IGF-II in Different Periods of Rat Liver Cancer.

OBJECTIVE: Based on liver cancer model built in SD rats, the contents of trace elements (Cu, Fe, Zn, Ca and Mg), AFP, CEA, SF, TH and IGF-II in serum were measured at different stages to explore the molecular changes during the rat liver cancer development. METHODS: The SD rat liver cancer model was built by using diethylnitrosamine (DENA) as the mutagen. During 16 weeks of DENA gavage, blood samples were taken in the 14th, 28th, 56th, 77th, 105th and 112th days respectively after the first day of gavage with DENA, then the contents of five trace elements (Cu, Fe, Zn, Ca and Mg), T3, T4, IGF-II, AFP, CEA and SF in serum were determined. RESULTS: During the development of the rat liver cancer, in the test group, the Cu content significantly increased in serum, while the contents of Fe, Zn and Ca significantly decreased. The content of Mg showed no significant change. AFP and CEA of the test group showed same expression level with the control group; while the content of SF was lower than that of the control group when cancerization appeared. T3 and T4 increased at the first stage and then went down, and the content of IGF-II was always high. CONCLUSION: Cu, Fe, Zn, Ca, T3, T4, SF and IGF-II are closely related to the development of liver cancer. The changes of their contents in the development of cancer could enlighten the researches on cancer pathogenesis and prevention.

[Effects of small interfering RNA approach to silence the connective tissue growth factor gene on the expression of the protein p27].

OBJECTIVE: To investigate the effects of the small interfering RNA (siRNA) approach to silence the expression of connective tissue growth factor (CTGF) gene expression on the expression of the protein p27. METHODS: Experimental research. The specific siRNA of CTGF was designed and synthesized, then transfected into cultured bovine corneal endothelial cells by liposomes. The blank control group was only treated with the culture medium and not be transfected with siRNA. Reverse transfection-polymerase chain reaction (RT-PCR) was applied to show the effect of gene-silencing, and western blot was used to observe the protein p27 expression of bovine corneal endothelial cells, which were treated with 1.00 µg/L transforming growth factor ß(2) (TGF-ß(2)). The results were analyzed by one-factor analysis of variance. RESULTS: CTGF siRNA was successfully transfected into cultured bovine corneal endothelial cells and effectively silence the expression of CTGF mRNA. The CTGF mRNA expression decreased to 17.3%, 24.4% and 41.7% of control values at 24, 48 and 72 h after transfection, there was significant difference between these groups (F = 389.9, P < 0.05). Significant decrease of protein p27 expression was detected at 36 h after transfection (F = 299.3, P < 0.05). CONCLUSION: CTGF-specific siRNA was able to inhibit the expression of CTGF mRNA effectively and down-regulate the expression of p27.

[RNA interference targeting aquaporin-1 on inhibition of human vascular endothelial cell migration in vitro].

OBJECTIVE: To investigate inhibition of human vascular endothelial cell migration in vitro by RNA interference targeting AQP-1, and the mechanism of corneal neovascularization. METHODS: Experiment research. Human umbilical vein endothelial cell (HUVEC) was cultured, AQP-1 specific siRNA was designed and synthesized. siRNA was transfected into the HUVEC by Lipofectamine 2000. The mRNA of AQP-1 was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Transwell migration assay and wound healing assay were used to detect the migration capability of HUVEC. The group comparison of AQP-1 mRNA expression was used one-way ANOVA test The result of transwell migration assay and wound healing assay was analysed with Independent-Sample T test. RESULTS: The expression of AQP-1 mRNA was significantly (P < or = 0.05) suppressed after transfection. 24 h, 48 h and 72 h, after transfection, the expression of AQP-1 mRNA was 11.3%, 17.4% and 29.7% respectively compared to normal control (P = 0.004, 0.007, 0.002). Transwell migration assay and wound healing assay showed that the migration capability of HUVEC was decreased obviously (t = 10.813, P = 0.016 and t = 22.431, P = 0.027). CONCLUSIONS: AQP-1 specific siRNA is effective in suppressing the AQP-1 expression and inhibiting the migration of the cultured HUVEC. Reducing the expression of AQP-1 can inhibit the corneal neovascularization.

[Expression and significance of Hsp70 and PCNA during the development of forestomach carcinoma in NIH mice].

AIM: To explore the expressions and significance of heat shock protein 70 (Hsp70) and proliferating cell nuclear antigen (PCNA) in the development of forestomach carcinoma in NIH mice induced with N-Nitrososarcosineethylester(NSEE). METHODS: 144 mice were divided into 6 groups and their stomachs were infused with NSEE. Then 24 mice were killed every two weeks and their forestomachs were used for the study of the expressions of Hsp70 and PCNA by immunohistochemical staining. RESULTS: With the progress of carcinogenesis, the expression pattern of Hsp70 was up-down-up, but the expression trend was still increasing. On day 56 and day 70 after NSEE treatment, the expression level of Hsp70 was higher than that of control (P<0.05). On day 84, the expression level of Hsp70 was markedly higher than that of control (P<0.01). The expression of PCNA increased gradually with the carcinogenesis. As compared with the control, stronger expression was found on day 42 and day 56 (P<0.05) and notably stronger expression on day 84 (P<0.01). The expression of Hsp70 was positively correlated to that of PCNA (r=0.98, P<0.01). CONCLUSION: In the development of forestomach carcinoma of NIH mice, the expressions of both Hsp70 and PCNA increased and were positively correlated with each other.