The association between liver cirrhosis and fracture risk: A systematic review and meta-analysis.

OBJECTIVE: Liver cirrhosis (LC) was associated with an increased risk of osteoporosis; however, the association between LC and fracture risk was inconclusive. Therefore, this systematic review and meta-analysis aims to explore the association between LC and fracture risk. DESIGN: To identify related literature, a systematic search of PubMed, EMBASE, Web of science and the Cochrane Library from 1965 to July 2017 without language limitation was performed. The random-effects model described by DerSimonian and Laird was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Eventually, 5 cohort and 3 case-control studies were identified, which included 321 035 subjects and 31 272 fracture cases. The pooled OR of the association between LC and any fracture risk, hip fracture, spine/trunk fracture and limb fracture was 1.94 (95% CI, 1.59-2.37), 2.11 (95% CI, 1.34-3.32), 2.00 (95% CI, 1.50-2.67) and 1.82 (95% CI, 1.65-2.01), respectively. CONCLUSION: In conclusion, this study indicates that cirrhotic patients have an increased risk of fracture. Preventive measures should be instituted as early as possible.

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides.

An efficient palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides has been developed. The reaction proceeds under mild reaction conditions with high efficiency and excellent functional group tolerance, even towards formyl and hydroxy groups. Preliminary mechanistic studies reveal that a secondary trifluoromethylated alkyl radical is involved in the reaction.

Elevated Serum Brain-Derived Neurotrophic Factor (BDNF) but not BDNF Gene Val66Met Polymorphism Is Associated with Autism Spectrum Disorders.

The aim of our study was to illuminate the potential role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder (ASD). We measured the circulating levels of BDNF in serum and BDNF gene (Val66Met) polymorphisms, in which two indicators were then compared between ASD and normal controls. A total of 82 drug-naïve ASD children and 82 age- and gender-matched normal controls were enrolled in the study. Their serum BDNF levels were detected by the ELISA. BDNF Val66Met polymorphism genotyping was conducted as according to the laboratory's standard protocol in laboratory. The ASD severity assessment was mainly determined by the score of the Childhood Autism Rating Scale (CARS). ELISA assay showed that the mean serum BDNF level of children with ASD was significantly (P < 0.0001) higher than that of the control cases (17.75 ± 5.43 vs. 11.49 ± 2.85 ng/ml; t = 9.236). Besides, the serum BDNF levels and CARS scores (P < 0.0001) were positively related. And, the BDNF genotyping results showed that there was no difference between the ASD cases and the control. Among the children with ASD, the mean serum BDNF level of Met/Met group was lower than other groups. According to the ROC curve generated from our clinical data, the optimal cutoff value of serum BDNF levels, an indicator for diagnosis of ASD, was projected to be 12.50 ng/ml. Thus, it yielded a corresponding sensitivity of 81.7 % and the specificity of 66.9 %. Accordingly, area value under the curve was 0.836 (95 % CI, 0.774-0.897); the positive predictive value (PPV) and the negative predictive value (NPV) were 70.1 and 79.1 %, respectively. These results suggested that rather than Val66Met polymorphism, BDNF was more possible to impact the pathogenesis of ASD.

Comparison of circumferential pulmonary vein anatomy mapping guided by 3D mapping versus a mesh mapping catheter.

OBJECTIVE: Catheter-based pulmonary vein isolation (PVI) is an established therapy for paroxysmal atrial fibrillation. The high-density mesh mapper (HDMM) guides circumferential PV-atrium isolation without the 3D electroanatomic mapping. This study aims to compare circumferential pulmonary vein (CPV) anatomy mapping between guiding by a 3D mapping system and the HDMM. METHODS: Forty-four consecutive patients with paroxysmal atrial fibrillation were scheduled for a first procedure for PVI. A CPV ostial anatomy map guided by HDMM was set up in the CARTO system while the operator was blinded to the CARTO screen. Then CARTO-guided ipsilateral PV maps were obtained and PVI was performed. This established another set of CPV ostial anatomy maps. The differences between the two mapping images were compared and analyzed. RESULTS: All 176 PVs in 44 patients could be mapped by both HDMM and CARTO. About 44.9% of the PV ostial anatomies were generally similar between the two different map images. The average point-to-point straight distance between the HDMM-guided map and the CARTO-guided map was 6.2 ± 1.4 mm. The area of the circumferential right PV (CRPV) in the HDMM map was larger than that in the CARTO map (P = 0.013). After a mean follow-up of 18.3 ± 4.3 months (6-24 months), 72.7% of patients (32/44) were free of atrial arrhythmia without anti-arrhythmic drugs (AADs). CONCLUSION: Compared to the CARTO-guided CPV anatomy image, a highly similar figure could be achieved by mapping guided by the HDMM. (Clinical trial.gov number, ChiCTR-TNRC-11001390.).

Fluorinated nucleosides as antiviral and antitumor agents.

The synthesis of nucleosides and analogues with fluoride modifications on the surgar moiety are reviewed, and their biological activities as potential antiviral and anti-tumor agents are also discussed.

Synthesis of gem-difluoromethylenated daidzein analogues and their inhibitory effect on U2OS cell cycle.

gem-Difluoromethylenated daidzein analogues 2 and 4 were obtained by the insertion reaction of difluorocarbene. A series of alkylated fluorine-containing daidzein analogues 3a-f and 5a-f were synthesized. All the compounds were tested for the inhibitory effect on U2OS cell cycle in vitro. The results showed that 7-octyloxy-3-(4-difluoromethoxyphenyl)-chromen-4-one 5d was the most active inhibitor.

[Histopathological changes post cryoablation in canine myocardium].

OBJECTIVE: The purpose of this study was to observe histopathological changes post cryoablation in canine myocardium, to characterize the specific ablation lesion post cryoablation. METHODS: Cryothermal ablation was applied on myocardium (both epicardium and endocardium) of 14 mongrel dogs with different ablation parameters (-25 degrees C x 4 min, -50 degrees C x 4 min, -75 degrees C x 4 min, -75 degrees C x 2 min, -75 degrees C x 6 min, -75 degrees C x 8 min). Lesion dimensions and histopathologic changes were observed. RESULTS: The discrete, sharply delimited lesions were detected in cryoablated myocardium. Histologically, cryoablation in all temperatures studied induced heterogeneous necrosis of the myocardium. Lesion dimensions are related to freezing time and temperature. CONCLUSION: Cryoablation is a feasible and preferably choice for clinical application due to its controllable myocardium lesions.

Synthesis and transformation of [difluoro(phenylseleno)methyl]- trimethylsilane.

[reaction: see text] A novel and efficient strategy was developed to synthesize [difluoro(phenylseleno)methyl]trimethylsilane (PhSeCF(2)TMS, 2), which was further utilized as a nucleophilic difluoromethylating reagent to incorporate the difluoro(phenylseleno)methyl (PhSeCF(2)) group into carbonyl compounds in good yields. The resulting PhSeCF(2)-containing alcohols 3 could be conveniently converted into corresponding difluoromethyl alcohols 4 by a radical deselenylation.

Trifluoromethylation of flavonoids and anti-tumor activity of the trifluoromethylated flavonoid derivatives.

3-Trifluoromethylflavonoid derivatives were prepared for the first time by trifluoromethylation of 3-iodoflavonoid derivatives. Other C ring and B ring trifluoromethylated flavonoid derivatives were also prepared. All the compounds were tested for their effect on the U2OS cell cycle in vitro. Bistrifluoromethylated apigenin derivative 13 showed the strongest activity against the cell growth.

[Comparison of different pacing sites of the right ventricle on left ventricular mechanical synchrony and systolic performance using tissue Doppler imaging].

OBJECTIVE: Right ventricular apical pacing may induce cardiac desynchronize and deteriorate left ventricular systolic performance. We hypothesized that right ventricular outflow tract (RVOT) pacing could produce better mechanical synchrony and left ventricular contraction. METHODS: We enrolled nine patients without structural heart disease who underwent electrophysiological studies. The pacing sites (right apex, low septum, free wall and septum of RVOT of the right ventricle) were defined with fluoroscopy and ECG. The atrioventricular sequential pacing was applied every 5 minutes in a random order at a rate of 120 bpm. Tissue Doppler imaging was carried out with GE VIVID 7 for off-line analysis at each pacing site. The global systolic contraction amplitude (GSCA) was calculated as the average shortening amplitude of all 16 segments of left ventricle. RESULTS: The GSCA during pacing was 5.76 mm +/- 0.66 mm at free wall of RVOT and 5.66 mm +/- 1.00 mm at septum of RVOT, respectively. The GSCA at both sites was significantly higher than that at apical pacing 4.82 mm +/- 0.94 mm (P < 0.05) or low septum pacing 4.82 mm +/- 1.06 mm (P < 0.05). Moreover, segmental displacement analysis showed that the longitudinal displacement of lateral, posterior, and inferior walls significantly decreased at apical pacing compared with RVOT pacing, although no difference could be demonstrated in anterior and septum walls. Accordingly, the curve of the myocardial displacement at apical or low septum pacing was M-shaped, and had a negative wave at the end of the diastole in lateral, posterior, and inferior walls. The tissue velocity during isovolumic contraction period was also higher than systolic tissue velocity in these walls. The phenomenon could seldom be seen at RVOT pacing. CONCLUSION: RVOT pacing in patients without structural heart disease is associated with more favorable immediate myocardial contraction and mechanical synchrony compared with right apical pacing or low septum pacing.

Synthesis of 2',3'-dideoxy-6',6'-difluorocarbocyclic nucleosides.

2',3'-Dideoxy-6',6'-difluorouracils, a novel series of gem-difluoromethylenated carbocyclic nucleosides, were synthesized from (Z)-but-2-ene-1,4-diol in 14 steps. A notable step was the construction of the carbocyclic ring via ring-closing metathesis and the incorporation of gem-difluoromethylene group by way of silicon-induced Reformatskii-Claisen reaction of chlorodifluoroacetic ester 3.

Synthesis of new 2',3'-dideoxy-6',6'-difluoro-3'-thionucleoside from gem-difluorohomoallyl alcohol.

[reaction: see text] 2',3'-Dideoxy-6',6'-difluoro-3'-thionucleoside 1b, an analogue of 3Tc that has high biological activities against HIV and HBV, has been synthesized from gem-difluorohomoallyl alcohol 3 in an efficient way. The key intermediate 4-amino-3,3-difluorotetrahydrothiophen-2-ylmethyl benzoate 15 was prepared from 2,2-difluoro-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]but-3-en-1-ol 3 in 11 steps. The construction of pyrimidine ring with the amino group of compound 15 gave the target compound 1.

3-deoxy-3,3-difluoro-D-arabinofuranose: first stereoselective synthesis and application in preparation of gem-difluorinated sugar nucleosides.

The design and synthesis of gem-difluorinated sugar nucleosides were described. The key intermediate, 3-deoxy-3,3-difluoro-d-arabinofuranose 9, was first stereoselectively prepared from the chiral gem-difluorohomoallyl alcohol 12. The kinetic formation of single anti-14 in the benzylation of 12 could be accomplished by controlling the amount of sodium hydride used. The dihydroxylation of 14 (a mixture of anti and syn isomers) followed by deprotection and oxidation stereoselectively afforded furanose 9 with the arabino configuration at the C2 position. N(1)-(3-Deoxy-3,3-difluoro-beta-D-arabinofuranosyl)cytosine 6 was prepared from 9 by the glycosylation reaction. 4'-Thiofuranose 25 was easily synthesized from 9. The oxidation of 25 followed by the condensation with silylated N(4)-benzoylcytosine (Pummerer reaction) failed to give our desired protected nucleoside l-3'-deoxy-3',3'-difluoro- 4'-thiocytidine 27', but the regioisomer 27 was obtained. The regiochemistry of the Pummerer reaction was determined by the kinetic acidity of the alpha-proton of 4'-thiofuranose 25.

Synthesis and anticancer effect of B-ring trifluoromethylated flavonoids.

A series of B-ring trifluoromethylated flavonoids derivatives were prepared and tested in vitro against human gastric adenocarcinoma cell line (SGC-7901). Among these derivatives, 5,7-dipropoxy-2-(4'-trifluoromethylphenyl)-chromen-4-one 5c had the strongest activity against SGC-7901 cell.

Synthesis and anticancer effect of chrysin derivatives.

A series of chrysin derivatives, prepared by alkylation, halogenation, nitration, methylation, acetylation and trifluoromethylation, were tested in vitro against human gastric adenocarcinoma cell line (SGC-7901) and colorectal adenocarcinoma (HT-29) cells. Among these derivatives of chrysin, 5,7-dimethoxy-8-iodochrysin 3 and 8-bromo-5-hydroxy-7-methoxychrysin 11 have the strongest activities against SGC-7901 and HT-29 cells, respectively. 5,7-Dihydroxy-8-nitrochrysin 12 were found to have strong activities against both SGC-7901 and HT-29 cells.