Synthesis of oxindoles bearing a stereogenic 3-fluorinated carbon center from 3-fluorooxindoles.

3,3-Disubstituted oxindoles bearing a stereogenic 3-fluorinated carbon center are privileged structural motifs present in many bioactive molecules. The straightforward functionalization of 3-fluorooxindoles constitutes a powerful method for the synthesis of 3-fully substituted 3-fluorooxindoles, taking advantage of the ease of preparation of 3-fluorooxindoles with different substitution patterns and the atom efficiency of chemical reactions. In the past decade, many papers have appeared on the synthesis of 3-fully substituted 3-fluorooxindoles from 3-fluorooxindoles. Importantly, many asymmetric catalytic methods have been developed for the enantioselective synthesis of these valuable compounds. This review summarizes the achievements in this area, and overviews synthetic opportunities that still exist.

Correlation between the Incidence of Allergic Rhinitis and the Environmental Air Quality in Zibo Area.

Objective To investigate the correlation between the incidence of allergic rhinitis (AR) and the air quality in Zibo area. Methods The number of AR cases in the outpatient departments of eight hospitals in five districts and three counties of Zibo city from January 2014 to December 2016 and the monthly change of the air pollution index (API) in Zibo area provided by Zibo Environment Protection Bureau during the same period were analyzed.Results The highest AR visit rates were recorded in April,May,and December,and the API was the highest in November,December,and January. The average AR visit rate in 2014,2015 and 2016 was 0.180±0.059,0.230±0.085,and 0.220±0.059 (F=2.251,P=0.123),and the average API was 113.26±20.152,126.81±30.688,and 112.58±22.934 (F=1.237,P=0.303). Pearson correlation analysis showed that the AR visit rate was positively correlated with the API (r=0.467,P=0.004). Conclusion The diagnostic rate of AR in Zibo area is positively correlated with the severity of air pollution.

Prevalence of stroke and associated risk factors among middle-aged and older farmers in western China.

OBJECTIVES: China has the world's largest population and the stroke has become the leading cause of death in recent years. The purpose of this study was to explore the associations between hypertension, family history of stroke, diabetes mellitus, obesity and stroke among middle-aged and older farmers of western China. A population-based study was conducted from June 2014 to April 2015 in Shaanxi and Sichuan provinces. METHODS: Twenty thousand five hundred twenty-five Chinese middle-aged and older farmers (≥40 years) were recruited to the Qinling-Daba Mountains Region Stroke Study. A structured-questionnaire was used to collect data through face-to-face interviews. Demographic characteristics, risk factors, medical history, and other clinical characteristics were recorded for all participants. The association between hypertension, family history of stroke, diabetes mellitus, obesity and stroke were analyzed by using univariate and multivariate logistic regression analysis. RESULTS: The stoke prevalence rate was 1380/100,000 in middle-aged and older farmers of western China. The difference in hypertension, diabetes mellitus, obesity and family history between different age groups had statistical significance (p < 0.05). The prevalence rate of hypertension and family history of stroke were higher in male population than in the female population. The difference was statistically significant (p < 0.05). Univariate logistic regression analysis demonstrated age, gender, hypertension, obesity and family history of stroke were stroke risk factors (p < 0.05). Multivariate logistic regression analysis revealed that the odds ratios of family history of stroke, obesity and hypertension were 7.177, 4.389 and 3.647 respectively. CONCLUSIONS: Family history is the strongest stroke risk factor in middle-aged and older farmers of western China.

[Downregulation of PTTG1 expression inhibits the proliferation and invasiveness and promotes the apoptosis of human prostate cancer LNCaP-AI cells].

OBJECTIVE: To investigate the effects of down-regulation of PTTG1 expression on the proliferation, invasiveness and apoptosis of androgen-independent human prostate cancer LNCaP-AI cells and their sensitivity to androgen antagonists. METHODS: Human prostate cancer LNCaP-AI cells were transfected with siRNA targeting the PTTG1 gene using the Lipofectamine 2000 transfection reagent. The proliferation, invasiveness and apoptosis of the cells were detected by MTT, Transwell assay and flow cytometry, respectively. The protein expressions of PTTG1, p-Akt, and p-ERK were determined by Western blot and the mRNA expression of PTTG1 measured by agarose gel electrophoresis. RESULTS: The siRNA expression vector markedly down-regulated the expression of PTTG1, which effectively suppressed the proliferation of the LNCaP-AI cells, with the inhibition rates of (19.47 ± 2.12), (24.01 ± 2.13) and (48.02 ± 2.22)% at 24, 48 and 72 hours, respectively, after transfection, with statistically significant differences among the three groups (P <0.05). The number of the cells passing through the polycarbonate film was remarkably decreased at 24, 48 and 72 hours (74.67 ± 9.85, 56.44 ± 8.66 and 37.33 ± 6.14) as compared with the baseline (111.11 ± 13.47) (P <0.01), while the apoptosis rate of the cells was significantly increased at 24, 48 and 72 hours (18.32 ± 0.94), (19.94 ± 1.30) and (21.73 ± 1.88)% in comparison with the baseline (ï¼»2.17 ± 0.49ï¼½%)， (P <0.05). PTTG1 siRNA combined with androgen antagonist flumatide exhibited even more significant effects in inhibiting the proliferation and promoting the apoptosis of the LNCaP-AI cells than either used alone, and in a flumatide dose-dependent manner. The inhibition and apoptosis rates of the LNCaP-AI cells treated with 50 nmol/L flumatide were (27.13 ± 3.52) and (3.94 ± 0.48)%, and those treated with siRNA + 50 nmol/L flumatide were (67.51 ± 5.13) and (19.93 ± 1.72)%, respectively, both with statistically significant differences between the two groups (P <0.05). The inhibition and apoptosis rates of the cells treated with 100 nmol/L flumatide were (43.72 ± 3.90) and (5.33 ± 0.66)%, and those treated with siRNA + 100 nmol/L flumatide were (73.19 ± 4.78) and (23.43 ± 1.76)%, respectively, both with statistically significant differences between the two groups (P <0.05). CONCLUSIONS: The siRNA expression vector can down-regulate the expression of PTTG1, which can inhibit the proliferation and invasiveness of LNCaP-AI cells, promote their apoptosis, and increase their sensibility to androgen antagonists. Suppressing the expression of PTTG1 may enhance the effect of androgen-deprivation therapy on advanced prostate cancer.

[Expression of pituitary tumor-transforming gene 1 during the development of androgen-independent prostate cancer].

OBJECTIVE: To explore the expression of pituitary tumor transforming gene 1 (PTTG1) during the transformation of prostate cancer from androgen-dependent (ADPC) to androgen-independent (AIPC). METHODS: We established an AIPC cell model LNCaP-AI by culturing the androgen-dependent LNCaP cell line in the hormone-deprived medium for over 3 months. The cell model was verified and the PTTG1 expression in the LNCaP cells was detected by Western blot and RT-PCR during hormone deprivation. RESULTS: The AIPC cell model LNCaP-AI was successfully established. The PTTG1 expression was gradually increased in the LNCaP cells with the prolonged time of hormone deprivation and the expressions of matrix metalloproteinases MMP-2 and -9 were elevated at the same time. CONCLUSIONS: The expression of PTTG1 is increased gradually in AIPC, which may be a target of gene therapy for advanced prostate cancer.

MEX3A promotes nasopharyngeal carcinoma progression via the miR-3163/SCIN axis by regulating NF-κB signaling pathway.

Mex-3 RNA Binding Family Member A (MEX3A) is an RNA-binding protein that plays complex and diverse roles in the development of various malignancies. However, its role and mechanism in nasopharyngeal carcinoma (NPC) remain undefined and were therefore evaluated in this study. By analyzing Gene Expression Omnibus data and using tissue microarrays, we found that MEX3A is significantly upregulated in NPC and negatively associated with prognosis. Notably, MEX3A depletion led to decreased cell proliferation, invasion, and migration, but increased apoptosis in NPC cells in vitro, while inhibiting tumor growth in vivo. Using whole-transcript expression arrays and bioinformatic analysis, we identified scinderin (SCIN) and miR-3163 as potential downstream targets of MEX3A in NPC. The regulatory mechanisms of MEX3A, SCIN and miR-3163 were further investigated using rescue experiments. Importantly, SCIN depletion and miR-3163 inhibition reversed and rescued the oncogenic effects of MEX3A, respectively. Moreover, NF-κB signaling inhibition reversed the oncogenic effects of both SCIN and MEX3A. In summary, our results demonstrate that MEX3A may promote NPC development and progression via the miR-3163/SCIN axis by regulating NF-κB signaling, thus providing a potential target for NPC treatment.

A pyridyl-decorated Zr-organic framework for enhanced gas separation and CO2 transformation.

A Zr-based MOF with UiO-66 topology, which was defined as Py-UiO-66, has been synthesized by modifying the ligand of p-phthalic acid with a pyridine group. Py-UiO-66 possesses excellent chemical stability in aqueous solutions of pH = 0-13, especially when the pore structure is functionalized by hanging bare Lewis basic pyridine groups. Results of gas adsorption experiment show that Py-UiO-66 has the ability to selectively absorb C2H2 and CO2 rather than CH4. More importantly, Py-UiO-66 has an efficient catalytic effect in CO2 cycloaddition.

Distribution and colocalization of melatonin 1a-receptor and NADPH-d in the trigeminal system of rat.

Melatonin and nitric oxide (NO) are involved in orofacial signal processing in the trigeminal sensory system. The aim of the present study was to examine the distribution of melatonin 1a-receptor (MT1) and its colocalization with nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the spinal trigeminal nucleus (STN), the trigeminal ganglion (TG), and the mesencephalic trigeminal nucleus (MTN) in the rat, using histochemistry and immunohistochemistry. Our results show that MT1-positive neurons are widely distributed in the TG and the subnucleus caudalis of the STN. Furthermore, we found that MT1 colocalizes with NADPH-d throughout the TG and MTN, most extensively in the TG. The distribution pattern of MT1 and its colocalization with NADPH-d indicate that melatonin might play an important role in the trigeminal sensory system, which could be responsible for the regulation of NO levels.

Effect of temozolomide on survival in elderly patients with glioblastoma and impaired performance status: a propensity score-matching analysis.

OBJECTIVE: At present, there is no consensus regarding the standard treatment for glioblastoma (GBM) in elderly patients with impaired Karnofsky performance status (KPS) scores. This study aimed to determine the effects of temozolomide (TMZ) versus best supportive care (BSC) in this population. MATERIALS AND METHODS: We conducted a retrospective observational study of patients aged ≥65 years with histologically confirmed GBM and KPS scores ≤70 who were treated at our institution between January 2006 and July 2014. Demographic data, treatments, and outcomes were evaluated. Univariate and multivariate analyses were performed to identify the independent prognostic factors of overall survival (OS) and progression-free survival (PFS). The impact of TMZ on survival was analyzed by the application of propensity score matching of clinicopathological factors among patients who received TMZ vs BSC. RESULTS: There were 153 patients (86 men, 56.2%) in this study. The median patient age was 70 years (range: 65-83 years). The median KPS score was 60 (range: 30-70). Seventy-eight patients (51.0%) received TMZ, whereas 75 (49.0%) received BSC. Median OS and PFS were 6.0 and 4.5 months, respectively. Compared with BSC, TMZ was associated with improved OS (hazard ratio [HR]: 0.38, 95% CI: 0.17-0.70; P=0.002) and PFS (HR: 0.41, 95% CI: 0.21-0.76; P=0.003) after propensity score matching. Factors independently associated with OS were KPS score (HR: 2.11, 95% CI: 1.48-7.67; P=0.016), extent of resection (HR: 1.98, 95% CI: 1.45-5.14; P=0.026), and treatment group (HR: 0.49, 95% CI: 0.23-0.87; P=0.019). The most frequent toxicity in the TMZ group was myelosuppression. CONCLUSION: Compared with BSC, TMZ increased survival with acceptable toxicity in elderly GBM patients with KPS scores ≤70.

Association between STAT5 polymorphisms and glioblastoma risk in Han Chinese population.

The aim of this study was to investigate the associations between STAT5 gene polymorphisms and glioblastoma (GBM) risk predisposition. We undertook a case-control study to analyze two STAT5 polymorphisms (STAT5a rs11079041 and STAT5b rs2293157) in a Han Chinese population, by extraction of genomic DNA from the peripheral blood of 328 patients with glioma and 342 control participants, and performed STAT5 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in STAT5a rs11079041. Nevertheless, STAT5b rs2293157 G/T genotype was at increased risk of glioma (P=0.001). Furthermore, rs2293157T allele was more significantly prognostic in patients suffering from glioblastoma compared to other subtypes of gliomas (P<0.001; odds ratio (OR)=5.14, CI 95%: 2.70-9.79). These findings led us to conclude that polymorphism in STAT5b rs2293157 G/T was observed to be associated with susceptibility of glioblastoma. Nevertheless, further investigation with a later confirmation in another ethnical or geographical cohort is required.

Suture-free technique of extravesical ureteroneocystostomy with ring pin stapler: experimental study of canines. I. Preliminary results.

OBJECTIVES: To compare the mechanical and sutured ureteroneocystostomy in a canine model. METHODS: In 18 dogs, extravesical ureteroneocystostomy on 1 side was randomly assigned to end-to-side anastomosis performed with a titanium ring-pin stapler or interrupted absorbable sutures. To create the antireflux tunnel, the longitudinal line of the muscle layer was closed over the implanted ureter with titanium clips or sutures. At 3 months postoperatively, renal ultrasonography, intravenous urography, ascending cystography, the Whitaker test, and the macroscopic and microscopic results were assessed. RESULTS: The ureteroneocystostomy with the ring pin stapler and the antireflux tunnel construction with titanium clips had a 100% technical success rate. Compared with manual suturing anastomosis, the suture-free technique took a significantly shorter time and resulted in slightly, but not significantly, less ureteral obstruction after 3 months. One dog in group 2 had evidence of ureteral dilation and hydronephrosis compared with the normal contralateral side. No signs of stone formation, urinary cyst, or fistulas were found after either closure method. None of the 18 dogs demonstrated vesicoureteral reflux. Histologic examination showed no signs of acute inflammation or marked fibrosis in any of the 18 specimens. Moreover, the intrapelvic pressure in group 1 was approximately similar to that of the normal contralateral side. CONCLUSIONS: Ureteroneocystostomy performed with a titanium ring-pin stapler is feasible and faster than using conventional sutures. This suture-free technique is simple and safe, with possibly lower complication rates than a nonstented suture technique. Additional studies with a longer follow-up duration are needed to confirm these results.