Direct Synthesis of C4-Acyl Indoles via C-H Acylation.

The direct synthesis of C4-acyl indoles deprived of C2 and C3 substituents has proven to be challenging, with scarce efficient synthetic routes being reported. Herein, we disclose a highly site-selective palladium-catalyzed C-H acylation for the construction of C4-acyl indoles via a Catellani-Lautens cyclization strategy. In addition, we systematically studied the ortho C-H acylation mechanism of iodoaniline through density functional theory (DFT) calculations and combined experimental results to elucidate the principle of high chemoselectivity brought by triazine benzoate as an acylation reagent.

Study on the correlation between false-positive filling defect in LAA CT and LAA structure in patients with atrial fibrillation based on TEE.

OBJECTIVE: This study aims to explore the actual meaning of "false positive filling defect" in left atrial appendage (LAA) computed tomography (CT) in patients with atrial fibrillation (AF), with transesophageal echocardiography (TEE) as the gold standard. METHODS: Patients with AF undergoing cardiac CT angiography and TEE examinations for proposed radiofrequency catheter ablation between October 2020 and October 2021 were selected as the study subjects. Transesophageal echocardiography was taken as the "gold standard," and spontaneous echocardiographic contrast (SEC) and thrombus events were defined as positive events. The CT manifestations were classified into three groups (true positive, false positive, and true negative) to evaluate the differences in left atrium (LA) anterior-posterior diameter (LAAP), LA anterior wall thickness, and LAA orifice long diameter and short diameter, area, and depth between the three groups. RESULTS: (1) There was no statistical difference in LA anterior wall thickness between the three groups (p > .05); there was a statistical difference in LAAP (only) between the true-positive group and the true-negative group (p < .05). (2) There was a statistical difference in LAA orifice long diameter, short diameter, and area between the true-positive group and the true-negative group as well as between the false-positive group and the true-negative group (p < .05). (3) There was a statistical difference in LAA depth between the true-positive group and the false-positive group as well as between the true-positive group and the true-negative group (p < .05). (4) The area under the receiver operator characteristic curve (AUC) of LAA depth affecting the LAA thrombus and SEC was 0.863 (confidence interval = 0.718-1.000), the sensitivity was 77.8%, and the specificity was 90.6% for predicting the occurrence of LAA thrombus and SEC in patients with nonvalvular AF (NVAF) and an LAA depth of ≥50.84 mm. CONCLUSIONS: There was a difference in LAA diameter between the TEE-based CT false-positive group and the other groups. A "CT false positive" is an objectively existing state, and CT might be able to identify the LAA hemodynamic disorder earlier than TEE. Furthermore, a CT + TEE combined application could more accurately evaluate LAA hemodynamics in patients with AF.

Diagnostic performance of magnifying endoscopy with narrow-band imaging in differentiating neoplastic colorectal polyps from non-neoplastic colorectal polyps: a meta-analysis.

Colorectal polyps are commonly seen in colonoscopy and the management of neoplastic polyps and non-neoplastic polyps are different. It is necessary to distinguish neoplastic polyps from non-neoplastic polyps in real-time. Therefore, we conducted a meta-analysis to assess the diagnostic accuracy of magnifying endoscopy with narrow-band imaging (ME-NBI) in diagnosing neoplastic colorectal polyps from non-neoplastic colorectal polyps. PubMed and EMBASE were searched for trials that used magnifying endoscopy with ME-NBI for diagnosing neoplastic colorectal polyps. Sixteen articles and 20 fourfold tables were obtained. Sensitivity (Sen), specificity (Spe), positive likelihood ratios (+ LRs), negative likelihood ratios (- LRs) and diagnostic odds ratios (DORs) were calculated. A summary receiver-operating characteristic (SROC) curve was constructed, and the area under the ROC curve (AUC) was calculated. We performed subgroup analyses based on polyp size and assessment criteria: (1) According to data extracted from 20 fourfold tables, the pooled Sen and Spe of ME-NBI for diagnosing neoplastic colorectal polyps < 10 mm were 0.94 (95% CI 0.92-0.95) and 0.76 (95% CI 0.72-0.80),respectively. The pooled Sen and Spe of ME-NBI for diagnosing all neoplastic polyps were 0.98 (95% CI 0.98-0.99) and 0.88 (95% CI 0.85-0.90), respectively. (2) Data pertaining to the following three assessment methods were analysed from 15 fourfold tables: surface pattern (SP), vessel pattern (VP) and the combination of SP and VP. The AUCs for these assessment criteria were 0.9533, 0.9518 and 0.9954, respectively. Conclusions were made that ME-NBI has high diagnostic accuracy in diagnosing neoplastic colorectal polyps based on the combination of SP with VP and is helpful in making real-time diagnoses.

Anti-amnesic effect of Dendropanax morbifera via JNK signaling pathway on cognitive dysfunction in high-fat diet-induced diabetic mice.

The ameliorating effects of the ethyl acetate fraction from Dendropanax morbifera (EFDM) on cognitive impairment in high-fat diet (HFD)-induced diabetic mice were examined by measuring its possible pharmacological activities. Administration of EFDM (20 and 50mg/kg body weight) in HFD-induced diabetic mice significantly improved glucose tolerance status in the intraperitoneal glucose tolerance test (IPGTT). In animal experiments using Y-maze, passive avoidance and Morris water maze tests, the cognitive and behavioral disorders in HFD-induced diabetic mice were considerably recovered by regulating cholinergic systems, including acetylcholine (ACh) levels and acetylcholinesterase (AChE) inhibition, and antioxidant systems, including superoxide dismutase (SOD), glutathione (GSH), oxidized GSH, and malondialdehyde (MDA) levels. Furthermore, HFD-induced abnormal activity of mitochondria were also significantly protected by the improvement of the c-Jun N-terminal protein kinase (JNK) signaling pathway with phosphorylated JNK (p-JNK), phosphorylated insulin receptor substrate (p-IRS), serine/threonine protein kinase (Akt), phosphorylated Akt (p-Akt), and phosphorylated tau (p-tau). Finally, rutin, orientin, isoorientin, and luteolin-7-O-rutinoside as the main phenolics of EFDM were identified using ultra-performance liquid chromatography/quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS(2)). These findings suggest that EFDM may have an effect as a multiple preventive substances to reduce diabetes-associated cognitive dysfunction.

Antiamnesic Effect of Broccoli (Brassica oleracea var. italica) Leaves on Amyloid Beta (Aß)1-42-Induced Learning and Memory Impairment.

To examine the antiamnesic effects of broccoli (Brassica oleracea var. italica) leaves, we performed in vitro and in vivo tests on amyloid beta (Aß)-induced neurotoxicity. The chloroform fraction from broccoli leaves (CBL) showed a remarkable neuronal cell-protective effect and an inhibition against acetylcholinesterase (AChE). The ameliorating effect of CBL on Aß1-42-induced learning and memory impairment was evaluated by Y-maze, passive avoidance, and Morris water maze tests. The results indicated improving cognitive function in the CBL group. After the behavioral tests, antioxidant effects were detected by superoxide dismutase (SOD), oxidized glutathione (GSH)/total GSH, and malondialdehyde (MDA) assays, and inhibition against AChE was also presented in the brain. Finally, oxo-dihydroxy-octadecenoic acid (oxo-DHODE) and trihydroxy-octadecenoic acid (THODE) as main compounds were identified by quadrupole time-of-flight ultraperformance liquid chromatography (Q-TOF UPLC-MS) analysis. Therefore, our studies suggest that CBL could be used as a natural resource for ameliorating Aß1-42-induced learning and memory impairment.

Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid.

The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1 µg/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404).

Feasible endoscopic therapy for early gastric cancer.

AIM: To analyze the relationship between lymph node metastasis and clinical pathology of early gastric cancer (EGC) in order to provide criteria for a feasible endoscopic therapy. METHODS: Clinical data of the 525 EGC patients who underwent surgical operations between January 2009 and March 2014 in the West China Hospital of Sichuan University were analyzed retrospectively. Clinical pathological features were compared between different EGC patients with or without lymph node metastasis, and investigated by univariate and multivariate analyses for possible relationships with lymph node metastasis. RESULTS: Of the 2913 patients who underwent gastrectomy with lymph node dissection, 529 cases were pathologically proven to be EGC and 525 cases were enrolled in this study, excluding 4 cases of gastric stump carcinoma. Among 233 patients with mucosal carcinoma, 43 (18.5%) had lymph node metastasis. Among 292 patients with submucosal carcinoma, 118 (40.4%) had lymph nodemetastasis. Univariate analysis showed that gender, tumor size, invasion depth, differentiation type and lymphatic involvement correlated with a high risk of lymph node metastasis. Multivariate analysis revealed that gender (OR = 1.649, 95%CI: 1.091-2.492, P = 0.018), tumor size (OR = 1.803, 95%CI: 1.201-2.706, P = 0.004), invasion depth (OR = 2.566, 95%CI: 1.671-3.941, P = 0.000), histological differentiation (OR = 2.621, 95%CI: 1.624-4.230, P = 0.000) and lymphatic involvement (OR = 3.505, 95%CI: 1.590-7.725, P = 0.002) were independent risk factors for lymph node metastasis. Comprehensive analysis showed that lymph node metastasis was absent in patients with tumor that was limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement. CONCLUSION: We propose an endoscopic therapy for EGC that is limited to the mucosa, size ≤ 2 cm, differentiated and without lymphatic involvement.

Ameliorating effects of ethyl acetate fraction from onion (Allium cepa L.) flesh and peel in mice following trimethyltin-induced learning and memory impairment.

The anti-amnesic effects of onion (Allium cepa L.) flesh (OF)1 and peel (OP)2 on trimethyltin (TMT)3-induced learning and memory dysfunction were investigated to confirm learning and memory function. The inhibitory effect against cellular acetylcholinesterase (AChE)4 showed that the EtOAc fraction of OP (EOP5, IC50 value=37.11µg/mL) was higher than the EtOAc fraction of OF (EOF6, IC50 value=433.34µg/mL). The cognitive effects in ICR mice were also evaluated using Y-maze, passive avoidance, and Morris water maze tests. After the behavioral tests, AChE activity (control=100%, TMT=128%, EOF 20=108%, EOP 10=104%, and EOP 20=98%), superoxide dismutase (SOD)7 activity, oxidized glutathione (GSSG)8/total glutathione (GSH)9 and malondialdehyde (MDA)10 production were examined. These results indicate that both EOF and EOP improved learning and memory function. The main compounds of the EOF and EOP were analyzed by Q-TOF UPLC/MS, and the results were as follows: The EOF (quercetin and quercetin-4'-glucoside) and the EOP (quercetin-4'-glucoside and isorhamnetin-4'-glucoside). Consequently, our results suggest that both EOF and EOP could be efficacious in improving cognitive function through AChE inhibition and antioxidant activity in mice brains.

[The Efficiency and Complications of ESD and ESTD in the Treatment of Large Esophageal Mucosal Lesions].

OBJECTIVE: To study the efficiency and complications of endoscopic submucosal dissection (ESD) and endoscopic submucosal tunnel dissection (ESTD) in the treatment of large esophageal mucosal lesions. METHODS: The clinical data were collected from the patients who received ESD or ESTD for the treatment of early esophageal lesions in our hospital during January 1, 2014 to July 15, 2015, including the en bloc resection rate, curative resection rate, postoperative complication rate, the risk factors of complications were explored by univariate and multivariate analysis. RESULTS: A total of 50 patients were involved in the study, ESD or ESTD were performed successfully in 53 times, including 6 cases of ESD,47 cases of ESTD, The average age was (61.9 +/- 6.8) yr., the average operating time was (83.57 +/- 32.33) min, the average dissected lesion was (14.82 +/- 3.18) cm2, En bloc resection rate was 94.34%, the curative rate was 84.90%. There were 1 case of bleeding, 1 case of perforation, 45 (84.90%) cases of fever, 13 cases (24.53%) of esophageal stricture. The severity of stricture was associated with the operation time Codds ratio (OR) = 1.040, 95% confidence interal (CI): 1.007-1.075) and esophageal circumference (OR=9.972, 95% CI: 1.221-81.416). The residual resection margin appeared in 8 patients, and the lesion area (OR=1.145, 95% CI: 1.013-1.294) was the only risk factor. CONCLUSION: ESD and ESTD are safe and effective in the treatment of early esophageal lesions, but seems have relatively high incidence of esopgageal stricture and residual resection margin in the treatment of large esophageal lesions.

[Factors Associated with Successful Submucosal Tunneling Endoscopic Resection Treatment for Upper Gastrointestinal Submucosal Tumors].

OBJECTIVE: To determine the influence of location, depth and size of upper gastrointestinal (GI) submucosal tumors (SMTs) on the success of submucosal tunneling endoscopic resection (STER). METHODS: Patient records of 31 cases with upper GI SMTs who had STER between Jan. 1, 2014 and June 30, 2015 in West China Hospital of Sichuan University were retrieved. The success of STER was determined by its efficiency, complete resection rate, and incidence of complications. RESULTS: Of the 31 cases, 29 were treated successfully, with an average of (13.76 +/- 9.70) min and (32.00 +/- 27.35) min for tunnel formation of esophageal and stomach mucosal tumors respectively (P = 0.045). The 2 unsuccessful cases were gastric tumors. SMTs resection for mucous layer and muscularis propria took (17.50 +/- 9.06) min and (36.24 +/- 15.68) min, respectively (P=0.004). SMTs resection for tumors diameter < 2.0 cm and > or = 2.0 cm took (25.78 +/- 12.13) min and (39.73 +/- 19.23) min, respectively (P=0.023). Six cases of gastric tumors from muscularis propria had complications (19.4%) during or after surgery. CONCLUSION: Location, depth and size of upper GI SMTs has implications on duration of different STER stages, which may determine complete resection rate and incidence of complications.

[Risk Factors of Lymph Node Metastasis in Superficial Esophageal Squamous Cell Carcinoma].

OBJECTIVE: To analysis the risk factors of lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (SESCC). METHODS: The clinical data and pathological results of 344 SESCC patients, who underwent surgical treatments between January 2009 and December 2013 in West China Hospital, Sichuan University, were analyzed retrospectively. Clinicopathologic characteristics were compared between different histological types, and their possible relationships with LNM were explored by univariate and multivariate analysis. RESULTS: There were no LNM found in the patients with tumor limited to the mucous, tumor diameter <3 cm, highly and moderate differentiated SESCC. Univariate analysis showed that tumor diameter (P=0.004), depth of tumor invasion (P=0.009), histological type (P=0.030) and lymphatic involvement (P=0.002) were correlated with LNM. Multivariate analysis revealed that tumor diameter (P=0.007), depth of tumor invasion (P=0.003), histological type (P=0.010) and lymphatic involvement (P<0.001) were independent risk factors of LNM. CONCLUSION: To the patients with low risk of LNM, such as tumor limited to the mucous, tumor diameter <3 cm, and highly and moderate differentiation, endoscopic excision may be considered as an absolute indications.

[Correlation Between Endoscopic Macroscopic Type and Depth of Tumor Invasion for Superficial Adenocarcinoma of Esophagogastric Junction].

OBJECTIVE: To investigate the clinicopathologic characteristics of superficial adenocarcinoma of esophagogastric junction (AEG), and to analyze the relationship between endoscopic macroscopic type and tumor depth for such cancers. METHODS: The clinical data of the 57 superficial AEG patients who underwent endoscopic resection or surgical operation between November 2008 and May 2015 in West China Hospital, Sichuan University were analyzed. Clinicopathologic features were compared between different depth of tumor invasion by univariate and multivariate analysis. RESULTS: The age ranged between 48 and 76 yr., with an average age of (63.0 +/- 6.8) yr.; 49 cases in male, 8 cases in female. The tumor size ranged between 3.0 and 40.0 mm, the average size was 16. 6 mm. The mucosal carcinoma was 28 cases, the submucosal carcinoma is 29 cases. There were no significant differences in age, gender, histological type and Siewert type in two groups, while there was statistical difference in tumor diameter (P=0.02) and endoscopic typing (P=0.02) between the two groups. The further multivariate analysis revealed that endoscopic macroscopic type (P=0.041) was an independent risk factor of superficial AEG invasion depth. The risk of submucosal invasion was 3.244 times in depressed type as.large as in elevated or flat type of the superficial AEG (95% confidence interval: 1.050-10.023). CONCLUSION: The endoscopic macroscopic type may be useful in accurately diagnosing superficial AEG invasion depth. For the endoscopic macroscopic type mainly of depression, especially the type 0-III, which was more likely to infiltrate the submucosal and more likely to have lymph node metastasis, do not recommend to get an endoscopic treatment.

[Application of flow cytometry-fluorescence in situ hybridization in the measurement of relative telomere length of bone marrow CD34(+) cells in patients with myelodysplastic syndrome].

This study was aimed to investigate the feasibility of flow cytometry-fluorescence in situ hybridization (Flow-FISH) in measuring the telomere length of bone marrow cell subgroups in patients with myelodysplastic syndrome (MDS). Seven newly diagnosed patients with low-risk MDS and seven nutritional anemia patients who were matched with age and sex, were enrolled in this study. Heparinized bone marrow were sampled. Taking Molt-4 cell line as internal control cells, leukocytes isolated from whole bone marrow were labeled with CD34-Alexa Fluork ® 647, then denatured by high temperature and hybridized with FITC-conjugated telomere probe. The DNA was counterstained and the relative telomere length (RTL) of nucleated cells and CD34(+) cells in bone marrow were measured by four-color flow cytometry. The results showed that CD34(+) cells could be gated for the measurement of RTL in both groups, undergoing the denaturation and hybridization. Primary analysis indicated that the RTL of bone marrow CD34(+) cells in MDS patients was significantly shorter than that of bone marrow nucleated cells (P = 0.001), and the RTL of both CD34(+) cells and nucleated cells in bone marrow of MDS patients were significantly shorter than that of control group (P = 0.020, 0.002). It is concluded that the application of Flow-FISH in the measurement of RTL of certain cell subgroup is feasible by labeling the cell with thermostable fluorescence-conjugated antibody, and this technique is worthy to be investigated further.

[First flush analysis of PAHs in roof runoff in Beijing].

Roof runoff samples of six storm events were collected at three different sites in the urban area of Beijing during the rainy season of 2008. The samples were analyzed for PAHs in both particle and dissolved phases. On the basis of the field measured data, the first flush phenomenon of PAHs was quantitatively analyzed using a newly defined FF(n-Max), and the influences of the storm event characteristics were discussed. In roof runoff, the first flush phenomena of total PAHs and PAHs in particle phase were noted, and PAHs in dissolved phase was not observed with first flush. The ranges of the first flush values for FF25 and FF30 were 0.6-2.4 and 0.6-2.1, respectively. For different types of roof materials, the strength of the first flush followed the order of: tile roof, cement roof > asphaltic felt roof. There is no significant difference between the tile roof and cement roof. No significant correlation was observed between the occurrence of first flush and the rainfall characteristics.