Diastereoselective Synthesis of Chromeno[3,2-d]isoxazoles via Brønsted Acid Catalyzed Tandem 1,6-Addition/Double Annulations of o-Hydroxyl Propargylic Alcohols.

A Brønsted acid catalyzed tandem process to access densely functionalized chromeno[3,2-d]isoxazoles with good to excellent yields and diastereoselectivities was disclosed. The procedure is proposed to involve a 1,6-conjugate addition/electrophilic addition/double annulations process of alkynyl o-quinone methides (o-AQMs) in situ generated from o-hydroxyl propargylic alcohols with nitrones. Mild conditions, good functional group compatibility, easy scale-up of the reaction, and further product transformation demonstrated its potential application.

The association between infectious burden and Parkinson's disease: A case-control study.

INTRODUCTION: The etiology of Parkinson's disease (PD) remains unclear. The aim of this study was to examine the association between common pathogenic infections and PD. METHODS: Antibody titers to common infectious pathogens including cytomegalovirus (CMV), Epstein Barr virus (EBV)，herpes simplex virus type-1 (HSV-1), Borrelia burgdorferi (B. burgdorferi), Chlamydophila pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) were measured by ELISA in serum of 131 PD patients and 141 normal controls. Infectious burden (IB) was defined as a composite serologic measure of exposure to these common pathogens. RESULTS: Seropositivities toward zero-two, three-four and five-six of these pathogens were found in 11%, 74% and 15% of normal controls while in 4%, 61% and 35% of PD patients, respectively. IB, bacterial burden and viral burden were independently associated with PD. Schwab and England (S&E) scores were negatively correlated with IB in patients with PD. Serum α-synuclein protein levels and inflammatory cytokines (interleukin-1ß and interleukin-6) in individuals with higher IB were also significantly higher. CONCLUSIONS: IB consisting of CMV, EBV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with PD. This study supports the role of infection in the etiology of PD.

Serum Aß is predictive for short-term neurological deficits after acute ischemic stroke.

Mounting evidence suggests that ischemic stroke (IS) is associated with Alzheimer's disease (AD). IS and vascular risk factors increase the risk for AD. However, whether AD pathologies exist in IS and the effects of these pathologies on stroke remain unknown. In the present study, we aimed to investigate the alterations of serum Aß after acute IS (AIS), and its correlations with the neurological deficits, infarction volume, and site after stroke. AIS patients (n = 35) were recruited within 24 h of symptom onset. Age- and gender-matched AD patients (n = 48) and cognitively normal controls (NC, n = 37) were also enrolled. Serum Aß40 and Aß42 and the National Institute of Health Stroke Scale Score (NIHSS) were measured on day 1, 3, and 7 after stroke onset. We found that serum Aß40 and Aß42 levels were increased at day 1 and reached peak levels at day 3, and decreased to pre-stroke levels at day 7. Serum Aß40 levels at day 1 were correlated with the NIHSS scores and infarction volume of AIS patients. Serum Aß42 levels at day 1 were significantly higher in IS patients with dominant gray matter infarction. Serum Aß40 levels at day 1 were predictive for NIHSS at day 7. Our results indicate that AIS can induce the generation of Aß in the brain, which may in turn be involved in the pathogenesis of neurological deficits after stroke. Serum Aß might be predictive for the short-term neurological deficits after AIS.

The relationship between single nucleotide polymorphisms of the NTRK2 gene and sporadic Alzheimer's disease in the Chinese Han population.

Alzheimer's disease (AD) is characterized by the degeneration of basal forebrain cholinergic neurons, whose survival and function are affected by neurotrophins and their receptors. The impaired signaling pathway of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) is considered to play an important role in AD pathogenesis. To explore the association of polymorphisms within the NTRK2 gene (encoding TrkB) and sporadic AD (sAD), a case-control study was conducted in a Chinese Han cohort including 216 sAD patients and 244 control participants. Five single nucleotide polymorphisms (SNPs), with four of them within the promoter region and one in intron, were selected and genotyped with a polymerase chain reaction-ligase detection reaction (PCR-LDR) method. No association was revealed between these SNPs or the haplotypes containing four promoter SNPs and the risk of sAD. The results of this study indicate that polymorphisms in the selected regions of the NTRK2 gene are unlikely to confer the susceptibility of sAD in the Chinese Han population.

No association of SORT1 gene polymorphism with sporadic Alzheimer's disease in the Chinese Han population.

Increasing evidence shows that sortilin (encoded by SORT1 gene), a member of the vacuolar protein sorting 10 family of sorting receptors, can modulate amyloid-ß peptides (Aß) metabolism and clearance, as well as mediate the neurotoxicity of the Aß oligomer and proneurotrophins, thus playing diverse roles in the pathogenesis of Alzheimer's disease. To assess the association between single nucleotide polymorphism (SNP) of the SORT1 gene and sporadic Alzheimer's disease (sAD) in the Chinese Han population, a case-control study was carried out including 220 sAD patients and 245 controls. One tag SNP was selected from the entire SORT1 gene through construction of linkage disequilibrium blocks, and three SNPs located in the vicinity of SORT1 that affect its expression were also selected. The four target SNPs were genotyped using a multiplex PCR-ligase detection reaction method, yielding no significant association between them or haplotypes containing three of them, and the risk of sAD. The results of this study indicate that polymorphisms of the SORT1 gene are unlikely to confer the risk of sAD in the Chinese Han population.

Characteristic transformation of blood transcriptome in Alzheimer's disease.

Blood transcriptome has emerged as a potential resource for the discovery of biomarkers for Alzheimer's disease (AD). However, the validity of blood transcriptome in the early diagnosis of AD has yet to be extensively tested. In this work, we analyzed published data on AD blood transcriptome and revealed the characteristic perturbation of cellular functional units, including upregulation of environmental responses (immune response, survival/death signaling, and cellular recycling) and down-regulation of core metabolism (energy metabolism and translation/splicing). This characteristic perturbation was unique to AD based on the comparison with blood transcriptome from other neurological disorders and complex diseases. More importantly, similar perturbation was observed in both AD and mild cognitive impairment (MCI) groups. This perturbation pattern was further validated in our independent microarray experiment in a small Chinese cohort. In addition, the potential effect of aging and lifestyle on blood transcriptome was discussed. Based on the analyses, we propose that the transformation of the blood transcriptome in AD is an integrated part of the disease mechanism and has potential to serve as a reliable biomarker for assisting the early diagnosis as well as monitoring purpose. Therefore, more independent studies on blood transcriptome of AD and MCI with larger sample size are warranted.

[Association between lymphangiogenesis and clinicopathological features and prognosis in laryngeal carcinoma].

OBJECTIVE: To detect lymphangiogenesis by labeling the lymphatic endothelial marker, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and study the prognostic relevance of lymphangiogenesis in laryngeal squamous carcinoma. METHODS: Clinical files and specimens of 78 patients with histologically diagnosed laryngeal carcinoma were stained with LYVE-1 as a specific lymphatic endothelial marker. The lymphatic vessel density (LVD) was measured, and the correlation between LVD and clinicopathological features of the tumor cases was analyzed. RESULTS: The mean LVD in laryngeal carcinoma (13.24 ± 5.09) was significantly higher than that in adult laryngeal papilloma (5.54 ± 3.15) and squamous dysplasia (6.76 ± 4.45, P < 0.05). The LVD of poorly differentiated tumors (15.74 ± 5.24) was significantly higher than that in the moderately differentiated tumors (13.84 ± 6.20), and the LVD in the moderately differentiated tumors was significantly higher than that in the well-differentiated tumors (11.68 ± 6.34). The LVD in stage 0 to stage II group (10.66 ± 5.70) was significantly lower than that in the stage III to IV group (17.01 ± 6.35). The lymph node metastasis group (17.25 ± 7.37) was significantly higher than non-lymph node metastasis group (8.60 ± 5.23, P < 0.05). There was no significant association between LVD and age, sex, primary site and distant metastasis. The overall survival in the patients with a LVD higher than the mean value was 33.5 month, and that of cases with a LVD lower than the mean value was 81.6 month (P < 0.05). The multivariate survival analysis showed that the clinical stage and LVD were independent prognostic factors of laryngeal cancer. CONCLUSIONS: The LYVE-1 staining histochemistry demonstrates that the lymphangiogenesis occurrs mainly at the edge of the tumors, and lymphangiogenesis plays an important role in the carcinogenesis, cancer progression and lymph node metastasis in laryngeal cancer. LVD may be an independent indicator of poor prognosis of laryngeal cancer.

[Vocal fold augmentation by injection of autologous fascia and fat].

OBJECTIVE: To evaluate the effect of combination of autologous fascia and fat injection into vocal fold for the treatment of patients with unilateral vocal fold paralysis and to observe the long-term effectiveness of this procedure. METHODS: A total of 26 unilateral vocal fold paralysis patients underwent vocal fold injection under general anesthesia, meanwhile, the mucosa of the injected point was sutured through laryngoscope under direct vision. There were 6 patients underwent autologous fat injection into vocal fold (group A), and 20 patients underwent autologous anterior rectus sheath fascia and fat injection (group B). Therapeutic efficacy were evaluated by videostroboscopy, voice-related parameters analysis and voice evaluation before and after treatment. Clinical analysis of this procedure was retrospectively performed in this serial of patients. RESULTS: All patients were followed up for 24 months. On the third day after operation, there was an acute inflammatory reaction induced by the graft. This reaction disappeared three months later. In all 20 cases, videolaryngostroboscopy showed significant improvement of the glottic closure, the improvement in acoustical parameters was statistically significant (P < 0.01). Perceptual evaluation of GRBAS scale showed significant improvement of phonatory function on G, B, A scale. The results remained stable 6 - 24 months after operation and were not changed by the length of follow-up. And in the 6 cases, videolaryngostroboscopy showed significant improvement of the glottic closure at 3 months compared with preoperative observation, a little spindle-shaped disclosure. The improvement in acoustical parameters was significant statistically at 3, 6 and 24 months (P < 0.05 or < 0.01), the voice quality decreased significantly at 6 and 24 months compared with 3 months (P < 0.05 or < 0.01). The significant differences were not observed between 6 and 24 months (P > 0.05). No complications were observed in all patients perioperatively or during the follow-up period. Voice-related parameters jitter, normalized noise energy and maximum phonation time showed significant differences between Group A and Group B on 24 months (P < 0.05 or < 0.01). CONCLUSION: The combination of autologous fascia and fat vocal fold injection is an effective procedure for the treatment of unilateral vocal fold paralysis, and the stable results can be achieved during the follow-up period for 24 months.

Correlations between psychological symptoms and social relationships among medical undergraduates in Anhui Province of China.

OBJECTIVES: To assess the prevalence of psychological symptoms (depression, anxiety) among Chinese medical students and to find the possible relationships between psychological symptoms and social relationships. METHODS: A sample of 10,140 medical students was investigated with a structured questionnaire, that included the Beck Depression Inventory, Beck Anxiety Inventory, Social Support Rating Scale, and Family APGAR Index (adaptability, partnership, growth, affection, resolve). RESULTS: The present study revealed that 16.8% of the medical students suffered from depressive symptoms and 14.1% from anxiety symptoms. Female students were more likely to have anxiety, the second-year students had higher levels of psychological symptoms than the first-year students. Likewise, significant differences were found among college, satisfaction of specialty, and economic condition of the family in anxiety and depression symptoms. Social support, family function, and all dimensions were significantly negatively associated with depression and anxiety symptoms. Multivariable ordinal logistic regression showed that less social support, poor family function, the second-year students, and unsatisfactory specialty were associated with more psychological symptoms, after adjusting the effects of sex, age, and college. CONCLUSIONS: Medical students have a relatively high level of depression and anxiety symptoms. These findings support the hypothesis that if medical students are better supported and cared for, negative psychosocial consequences might be prevented or at least reduced.

[Tubed pectoralis major myocutaneous flap for reconstruction of circumference pharyngoesophageal defects].

OBJECTIVE: To investigate the feasibility and efficacy of tubed pectoralis major myocutaneous flap in the reconstruction of circumferential defects following resection for locally advanced hypopharyngeal and cervical esophageal carcinoma. METHODS: From Dec. 2004 to Oct. 2008, 30 patients underwent immediate reconstruction by tubed pectoralis major myocutaneous flap for circumferential defects following resection of primary tumours. Among them, 22 were hypopharyngeal carcinoma, 7 were cervical esophageal carcinoma and one was recurrent laryngeal carcinoma involved the hypopharyngeal lumen. Five of 30 patients had received previous radiotherapy and three had failed in the previous surgical procedure. In this series, 12 patients had total pharyngolaryngectomy and 18 had total pharyngolaryngectomy and partial cervical esophagectomy. RESULTS: Postoperative pharyngocutaneous fistula formation occurred in 4 patients, 2 of them with previous radiotherapy and 2 with diabetes, and the fistulae healed later. Two patients developed anastomotic strictures at the upper junction, but they had good responses to dilatation treatment and had satisfactory oral intake. The postoperative follow-up time ranged from 8 to 56 months. Median follow-up was 18 months. One-year survival rate was 71.4% and three-year survival rate was 42.5%. CONCLUSIONS: The tubed pectoralis major myocutaneous flap is a reliable procedure to reconstruct hypopharyngeal circumferential defects following resection of advanced hypopharyngeal and cervical esophageal carcinoma. This method may be the optimal choice for the reconstruction of hypopharyngeal circumferential defects following resection of recurrent carcinoma. The incidence of fistula and stenosis could be kept at an acceptable level.

Methylenetetrahydrofolate reductase polymorphisms and susceptibility to gastric cancer in Chinese populations: a meta-analysis.

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are thought to have significant effects on folate metabolism and, thus, on cancer risk, but the reported results are not always consistent. In this meta-analysis including 2165 patients and 3279 controls, we assessed reported studies of associations between polymorphisms of MTHFR and susceptibility to gastric cancer in Chinese populations. An increased risk was found for MTHFR C677T in the meta-analysis [odds ratio (OR): 1.42; 95% confidence interval (CI): 1.24-1.62]. No association resulted for MTHFR A1298C (OR: 0.95; 95% CI: 0.78-1.17). Results from the subgroup analyses showed an increased risk for individuals with low (OR: 1.50; 95% CI: 1.18-1.91) versus high (OR: 1.21; 95% CI: 0.98-1.51) folate levels. The sensitivity analysis and publication bias diagnostics confirmed the reliability and stability of this meta-analysis. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis. Regarding cardia or noncardia gastric cancer, more studies are required for definite conclusions, as the number of studies is relatively small.

[Recurrent laryngeal nerve decompression].

OBJECTIVE: To study the result of recurrent laryngeal nerve decompression in the treatment of functional disturbance of recurrent laryngeal nerve caused by thyroid surgery or thyroid benign tumors. METHODS: From October 2002 to June 2005, 9 cases of unilateral recurrent laryngeal nerve paralysis and 4 cases of glottic insufficiency were treated with recurrent laryngeal nerve decompression. Seven cases of the nerve paralysis were caused by the surgery of benign thyroid tumors resection which were done by general surgeons. The paralysis nerve were found ligated in 6 of the 7 cases, and nerve-scar adhesion was found in the other case. Beside nerve decompression, type I thyroplasty have been undertaken in the same time to 2 of the 7 cases with severe hoarseness. One case of thyroid adenoma and 1 case of nodular goiter with unilateral recurrent laryngeal nerve paralysis were treated with tumor resection and nerve decompression respectively. Four cases of glottic insufficiency, 3 cases of nodular goiter were treated with tumor resection and nerve decompression, and Hashimoto's thyroiditis in the other case was treated with partial lobe resection and nerve decompression. The recovery of function of recurrent laryngeal nerve were detected to the recovery of vocal cord mobility through electrolaryngoscope postoperatively. RESULTS: For the 7 cases of recurrent laryngeal nerve paralysis after thyroid surgery, the motion of the paralysed vocal cord restored within 3 months in 6 cases with the interval of 1 week to 3 months between the two operations, no restoration was found in the other patient with an interval above 4 months between the two operations after 1 year follow-up. For the thyroid adenoma and nodular goiter with unilateral recurrent laryngeal nerve paralysis, the motion of paralysed vocal cord restored within 3 months respectively after decompression. The glottic closure recovered within 1 week after decompression in the 4 cases of the glottic insufficiency patient. CONCLUSIONS: Exploration and decompression as soon as possible to the paralysed recurrent laryngeal nerve because of thyroid surgery are very important for the restoration of the function of the nerve. For the patient with serve hoarseness, nerve decompression and type I thyroplasty at the same time is recommended in an effort to relieve hoarseness as soon as possible. For the functional disturbance of recurrent laryngeal nerve with thyroid neoplasm patient, early exploration and decompression of the nerve is imperative.