Green Late-Stage Functionalization of Tryptamines.

An efficient and rapid protocol for the oxidative halogenation of tryptamines with 10 % aqueous NaClO has been developed. This reaction is featured by its operational simplicity, metal-free conditions, no purification, and high yield. Notably, the resulting key intermediates are suitable for further functionalization with various nucleophiles, including amines, N-aromatic heterocycles, indoles and phenols. The overall transformation exhibits broad functional-group tolerance and is applicable to the late-stage functionalization of complex biorelevant molecules.

Changes and significance of vascular endothelial injury markers in patients with diabetes mellitus and pulmonary thromboembolism.

BACKGROUND: To investigate the changes and clinical significance of vascular endothelial injury markers in type 2 diabetes mellitus (T2DM) complicated with pulmonary embolism (PE). METHODS: This prospective study enrolled patients with T2DM hospitalized in one hospital from January 2021 to June 2022. Soluble thrombomodulin (sTM) (ELISA), von Willebrand factor (vWF) (ELISA), and circulating endothelial cells (CECs) (flow cytometry) were measured. PE was diagnosed by computed tomography pulmonary angiography (CTPA). RESULTS: Thirty participants were enrolled in each group. The plasma levels of sTM (151.22 ± 120.57 vs. 532.93 ± 243.82 vs. 1016.51 ± 218.00 pg/mL, P < 0.001) and vWF (9.63 ± 2.73 vs. 11.50 ± 2.17 vs. 18.02 ± 3.40 ng/mL, P < 0.001) and the percentage of CECs (0.17 ± 0.46 vs. 0.30 ± 0.08 vs. 0.56 ± 0.18%, P < 0.001) gradually increased from the control group to the T2DM group to the T2DM + PE group. sTM (OR = 1.002, 95%CI: 1.002-1.025, P = 0.022) and vWF (OR = 1.168, 95%CI: 1.168-2.916, P = 0.009) were associated with T2DM + PE. sTM > 676.68 pg/mL for the diagnosis of T2DM + PE achieved an AUC of 0.973, while vWF > 13.75 ng/mL achieved an AUC of 0.954. The combination of sTM and vWF above their cutoff points achieved an AUC of 0.993, with 100% sensitivity and 96.7% specificity. CONCLUSIONS: Patients with T2DM show endothelial injury and dysfunction, which were worse in patients with T2DM and PE. High sTM and vWF levels have certain clinical predictive values for screening T2DM accompanied by PE.

Effect of Calcium Hydroxide on Physicochemical and In Vitro Digestibility Properties of Tartary Buckwheat Starch-Rutin Complex Prepared by Pre-Gelatinization and Co-Gelatinization Methods.

This study examined the effect of calcium hydroxide (Ca(OH)2, 0.6%, w/w) on structural, physicochemical and in vitro digestibility properties of the complexed system of Tartary buckwheat starch (TBS) and rutin (10%, w/w). The pre-gelatinization and co-gelatinization methods were also compared. SEM results showed that the presence of Ca(OH)2 promoted the connection and further strengthened the pore wall of the three-dimensional network structure of the gelatinized and retrograded TBS-rutin complex, indicating the complex possessed a more stable structure with the presence of Ca(OH)2, which were also confirmed by the results of textural analysis and TGA. Additionally, Ca(OH)2 reduced relative crystallinity (RC), degree of order (DO) and enthalpy, inhibiting their increase during storage, thereby retarding the regeneration of the TBS-rutin complex. A higher storage modulus (G') value was observed in the complexes when Ca(OH)2 was added. Results of in vitro digestion revealed that Ca(OH)2 retarded the hydrolysis of the complex, resulting in an increase in values in slow-digestible starch and resistant starch (RS). Compared with pre-gelatinization, the complex process prepared with the co-gelatinization method presented lower RC, DO, enthalpy, and higher RS. The present work indicates the potential beneficial effect of Ca(OH)2 during the preparation of starch-polyphenol complex and would be helpful to reveal the mechanism of Ca(OH)2 on improving the quality of rutin riched Tartary buckwheat products.

Potential treatment benefits and safety of roflumilast in COPD: a systematic review and meta-analysis.

BACKGROUND: Current evidence suggests that roflumilast is efficacious in treating COPD, especially in preventing the acute exacerbation of COPD. OBJECTIVES: This study was designed to evaluate the clinical effects and safety of roflumilast in the treatment of stable COPD using randomized clinical trial (RCT) data. METHODS: A MEDLINE, EMBASE, and Cochrane Controlled Trials Register search was carried out. RCTs reporting the treatment effects of roflumilast in COPD were identified. Relevant data were extracted and a meta-analysis was performed. RESULTS: A total of nine articles and 13 RCT studies were identified. Overall, 29.1% of the subjects in the roflumilast group showed evidence of exacerbation. The corresponding figure was 32.2% in the placebo group. According to pooled analysis, the use of roflumilast reduced COPD exacerbations in comparison to placebo (odds ratio [OR] =0.82, 95% confidence interval [CI] =0.75-0.9). The quality of life and spirometry were improved. For patients receiving baseline pre-bronchodilators, their average forced expiratory volume in the first second showed evidence of change when they took roflumilast (64.88 mL; 95% CI =54.09-75.66). Those who took placebo showed no evidence of change. Similar result was observed in patients receiving baseline (54.49 mL; 95% CI =44.04-64.94). As for the safety of roflumilast treatment, the overall cumulative incidence of adverse drug reaction was 54.2% in the roflumilast group and 48.2% in the placebo group (OR =1.36, 95% CI =1.13-1.65). The adverse effects included diarrhea, headache, nausea, weight loss, and insomnia. CONCLUSION: The efficacy of roflumilast in the prevention of acute exacerbation of COPD is obvious. Roflumilast is proved to be able to improve spirometry of COPD patients. The adverse drug reaction did not increase significantly in the roflumilast group compared with the control group. COPD patients can benefit from roflumilast therapy. However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them; hence, more randomized trials are needed to further support this conclusion.

Elevated RABEX-5 expression predicts poor prognosis in non-small-cell lung cancer.

RABEX-5 has been studied in various solid tumors, but its role in non-small-cell lung cancer (NSCLC) remains unknown. This study is aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with NSCLC. A total of 120 NSCLC patients who underwent radical surgery between 2005 and 2010 were enrolled in the study. The clinicopathological data and survival time were reviewed. The mRNA and protein expression of RABEX-5 from the paired tumor specimens and adjacent normal tissues were determined, and its relationship with clinicopathological variables and prognosis was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of RABEX-5 for NSCLC. We found the mRNA and protein expression levels of RABEX-5 were significantly elevated in NSCLC tissues. The increased RABEX-5 expression was correlated strongly with tumor recurrence (P=0.005). The 5-year median OS and DFS were significantly shorter in the higher RABEX-5 expression group compared to that in the lower RABEX-5 expression group. Multivariate Cox analysis indicated that high RABEX-5 expression was an independent prognostic factor for OS and DFS (P<0.001). This data suggests that RABEX-5 is a potentially useful indicator for a poor prognosis for NSCLC.

High pretreatment serum C-reactive protein level predicts a poor prognosis for combined small-cell lung cancer.

High serum C-reactive protein (CRP) level is related to poor prognosis in several tumors. The aim of this study was to explore the prognosis value of serum CRP in patients with combined small-cell lung cancer (C-SCLC). The clinicopathological parameters of 112 C-SCLC patients from January 2000 to March 2009 were collected. The pretreatment serum CRP level was measured at diagnosis, and the correlation between serum CRP and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of these parameters for C-SCLC. The pretreatment serum CRP level was elevated in 52.7% of patients (E-CRP; n = 59), while (47.3%) within the normal range (N-CRP; n = 53). There was a significantly worse disease stage (p = 0.037) and higher neuronal specific enolase (NSE) level (p = 0.014) in the E-CRP group. The median overall survival (OS) was significantly longer in the N-CRP group than in the E-CRP group (22.0 vs. 11.5 months, respectively; p < 0.001). Multivariate analyses indicated serum CRP (hazard ratio (HR) = 2.1; p < 0.001), the extent of disease (HR = 1.3; p = 0.039), performance status (HR = 1.8; p = 0.012), and NSE (HR = 1.2; p < 0.001) as independent prognostic factors. High pretreatment serum CRP level predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other prognosticators in C-SCLC patients.

Elevated RABEX-5 protein expression predicts poor prognosis in combined small cell lung cancer.

RABEX-5 has been studied in various solid tumors, but its role in combined small cell lung cancer (C-SCLC) remains unknown. This study aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with C-SCLC. Fifty-two C-SCLC patients who received radical surgery were enrolled in our study. The clinicalpathological data and survival time were reviewed. The mRNA and protein expression of RABEX-5 from the paired tumor tissues and adjacent normal tissues were determined, and its relationship with clinicalpathological variables and prognosis was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of RABEX-5 for C-SCLC. The mRNA and protein expression level of RABEX-5 was significantly elevated in C-SCLC tissues. The increased RABEX-5 protein expression was correlated with clinical stage (p = 0.011) and tumor recurrence (p = 0.006). The median OS and DFS was significantly shorter in the high RABEX-5 expression group compared to low RABEX-5 expression group (OS: 12.0 vs. 21.7 months, p = 0.014; DFS: 6.7 vs. 11.8 months, p = 0.005). Multivariate Cox analysis indicated that high RABEX-5 protein expression was an independent prognostic factor for OS and DFS (p < 0.001). RABEX-5 is a potential useful indicator and predicts a poor long-term prognosis for C-SCLC, which should be considered in defining the prognosis with other well-known prognosticators in C-SCLC patients.