Sesquiterpenoids from the whole plants of Elephantopus mollis with cytotoxicity activities.

Five new sesquiterpenoids (1-5), elephantmollides A-E, along with four known compounds (6-9), were isolated from the whole plants of E. mollis. Their planar structures were elucidated using the spectroscopic methods, including HRESIMS, IR, UV, and NMR (1H, 13C, DEPT, HSQC, HMBC, 1H-1H COSY). The relative configurations of them were partially deduced by the NOESY experiment, and the absolute configurations were assigned by comparing the calculated electronic circular dichroism (ECD) results with the experimental data. In addition, cytotoxic activities of 1-9 against HepG2 cells ware tested, and compounds 1-9 exhibited cytotoxic activities with IC50 values ranging from 6.7 to 25.8 µM.

Lycopodium Alkaloids from Huperzia serrata and Their Anti-acetylcholinesterase Activities.

One new fawcettimine-type alkaloid (1), one new miscellaneous-type alkaloid (2), four new lycodine-type alkaloids (3-6), and eight known ones (7-14) were isolated from the whole plants of Huperzia serrata. Their structures and absolute configurations were elucidated based on spectroscopic data, X-ray diffraction, ECD calculation and Mosher's method. Compound 1 was a rare C18 N2 -type Lycopodium alkaloid, possessing serratinine skeleton with an amide side chain in C-5. The absolute configuration of the 18-OH of compounds 4-6 were first determined by Mosher's method. Moreover, compounds 1-14 were assayed anti-acetylcholinesterase effect in vitro, and compound 7 showed significant anti-acetylcholinesterase activity with an IC50 value of 16.18±1.64 µM.

Regular Aspirin Use Is Associated with a Reduced Risk of Hepatocellular Carcinoma (HCC) in Chronic Liver Disease: a Systematic Review and Meta-analysis.

PURPOSE: Aspirin reduces the incidence of various gastrointestinal (GI) malignancies. This meta-analysis assessed the efficacy and safety of regular aspirin use on the incidence of hepatocellular carcinoma (HCC) in patients with chronic liver disease. METHODS: Electronic reference databases were searched for studies in patients with chronic liver disease exposed to aspirin. The primary outcome was the incidence of HCC in regular aspirin users compared to non-users. The secondary outcome was the incidence of major GI bleeding events in both groups. The propensity score (PS) and non-PS-adjusted pooled hazard ratio (HR) were calculated using random-effects models. RESULTS: Six observational studies with 71,211 subjects were included. The median duration of follow-up ranged from 2.7 to 7.9 years. Four studies included patients with viral hepatitis; five studies used aspirin 100 mg/day. All six studies reported the non-PS-matched HR, and there was a 54% reduction in the incidence of HCC among regular aspirin users [HR (95% CI): 0.46(0.31-0.67), p < 0.001]. Four studies reported on the PS-matched HR; this showed a 46% reduced incidence of HCC in those using aspirin [HR (95% CI): 0.54(0.38-0.79), p < 0.001]. Subgroup analysis on studies restricted to viral hepatitis (n = 4) showed a 28% reduction in HCC incidence in aspirin users [HR (95% CI): 0.72(0.64-0.80), p < 0.001]. Four studies reported the incidence of major GI bleeds, there was no significant difference between the two groups [HR (95% CI: 1.00(0.69-1.45), p = 0.90]. All outcome analysis, except the subgroup analysis, had significant inter-study heterogeneity. CONCLUSION: Regular aspirin use in chronic liver disease is associated with reduced incidence of HCC without increasing the risk of major GI bleeding.

Diagnostic Accuracy of Artificial Intelligence (AI) to Detect Early Neoplasia in Barrett's Esophagus: A Non-comparative Systematic Review and Meta-Analysis.

Background and Aims: Artificial Intelligence (AI) is rapidly evolving in gastrointestinal (GI) endoscopy. We undertook a systematic review and meta-analysis to assess the performance of AI at detecting early Barrett's neoplasia. Methods: We searched Medline, EMBASE and Cochrane Central Register of controlled trials database from inception to the 28th Jan 2022 to identify studies on the detection of early Barrett's neoplasia using AI. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies - 2 (QUADAS-2). A random-effects model was used to calculate pooled sensitivity, specificity, and diagnostics odds ratio (DOR). Forest plots and a summary of the receiving operating characteristics (SROC) curves displayed the outcomes. Heterogeneity was determined by I 2, Tau2 statistics and p-value. The funnel plots and Deek's test were used to assess publication bias. Results: Twelve studies comprising of 1,361 patients (utilizing 532,328 images on which the various AI models were trained) were used. The SROC was 0.94 (95% CI: 0.92-0.96). Pooled sensitivity, specificity and diagnostic odds ratio were 90.3% (95% CI: 87.1-92.7%), 84.4% (95% CI: 80.2-87.9%) and 48.1 (95% CI: 28.4-81.5), respectively. Subgroup analysis of AI models trained only on white light endoscopy was similar with pooled sensitivity and specificity of 91.2% (95% CI: 85.7-94.7%) and 85.1% (95% CI: 81.6%-88.1%), respectively. Conclusions: AI is highly accurate at detecting early Barrett's neoplasia and validated for patients with at least high-grade dysplasia and above. Further well-designed prospective randomized controlled studies of all histopathological subtypes of early Barrett's neoplasia are needed to confirm these findings further.

Intelligent Extraction of Salient Feature From Electroencephalogram Using Redundant Discrete Wavelet Transform.

At present, electroencephalogram (EEG) signals play an irreplaceable role in the diagnosis and treatment of human diseases and medical research. EEG signals need to be processed in order to reduce the adverse effects of irrelevant physiological process interference and measurement noise. Wavelet transform (WT) can provide a time-frequency representation of a dynamic process, and it has been widely utilized in salient feature analysis of EEG. In this paper, we investigate the problem of translation variability (TV) in discrete wavelet transform (DWT), which causes degradation of time-frequency localization. It will be verified through numerical simulations that TV is caused by downsampling operations in decomposition process of DWT. The presence of TV may cause severe distortions of features in wavelet subspaces. However, this phenomenon has not attracted much attention in the scientific community. Redundant discrete wavelet transform (RDWT) is derived by eliminating the downsampling operation. RDWT enjoys the attractive merit of translation invariance. RDWT shares the same time-frequency pattern with that of DWT. The discrete delta impulse function is used to test the time-frequency response of DWT and RDWT in wavelet subspaces. The results show that DWT is very sensitive to the translation of delta impulse function, while RDWT keeps the decomposition results unchanged. This conclusion has also been verified again in decomposition of actual EEG signals. In conclusion, to avoid possible distortions of features caused by translation sensitivity in DWT, we recommend the use of RDWT with more stable performance in BCI research and clinical applications.

Two new clerodane diterpenoids and a new pyran-2-one derivative with anti-neuroinflammatory activities from Croton crassifolius.

Two new clerodane diterpenoids (1 and 2), a new pyran-2-one derivative (3), along with five known compounds (4‒8), were isolated from Croton crassifolius. Notably, crassifolin X (1) is a novel clerodane diterpenoid, characterized with a peculiar δ-lactone core being formed between C-1 and C-4. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (UV, IR, HRESIMS and NMR), and circular dichroism experiments. In addition, all compounds were evaluated for their anti-neuroinflammatory activities based on the expression of TNF-α and IL-6 levels on LPS-induced BV2 cells, and compounds 1‒3 and 5 showed potential anti-neuroinflammatory activity.

Suppressing of Power Line Artifact From Electroencephalogram Measurements Using Sparsity in Frequency Domain.

Electroencephalogram (EEG) plays an important role in brain disease diagnosis and research of brain-computer interface (BCI). However, the measurements of EEG are often exposed to strong interference of power line artifact (PLA). Digital notch filters (DNFs) can be applied to remove the PLA effectively, but it also results in severe signal distortions in the time domain. To address this problem, spectrum correction (SC) based methods can be utilized. These methods estimate harmonic parameters of the PLA such that compensation signals are produced to remove the noise. In order to ensure high accuracy during harmonic parameter estimations, a novel approach is proposed in this paper. This novel approach is based on the combination of sparse representation (SR) and SC. It can deeply mine the information of PLA in the frequency domain. Firstly, a ratio-based spectrum correction (RBSC) using rectangular window is employed to make rough estimation of the harmonic parameters of PLA. Secondly, the two spectral line closest to the estimated frequency are calculated. Thirdly, the two spectral lines with high amplitudes can be utilized as input of RBSC to make finer estimations of the harmonic parameters. Finally, a compensation signal, based on the extracted harmonic parameters, is generated to suppress PLA. Numerical simulations and actual EEG signals with PLA were used to evaluate the effectiveness of the improved approach. It is verified that this approach can effectively suppress the PLA without distorting the time-domain waveform of the EEG signal.

Water-soluble matrine-type alkaloids with potential anti-neuroinflammatory activities from the seeds of Sophora alopecuroides.

A phytochemical investigation on the alkaloids from water-soluble part of Sophora alopecuroides led to obtain forty matrine-type alkaloids (1-40) including eighteen new ones (1-18), which covers almost all positions of the oxygen substitution in matrine-type structure. Notably, eight compounds (1-8) belong to rare bis-amide matrine-type alkaloid. The new structures were determined based on extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and six instances, verified by X-ray crystallography. Most of isolates showed anti-neuroinflammatory activities based on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BV2 microglia cells. Especially, compound 39 can suppress those two mediator secretions in a dose-dependent manner with IC50 values of 21.6 ± 0.5 and 16.7 ± 0.8 µM, respectively. Further mechanistic study revealed that 39 suppressed the phosphorylation of IκBα and p65 subunit to regulate the NF-κB signaling pathway.

Nivolumab-induced myocarditis complicated by complete atrioventricular block in a patient with metastatic non-small cell lung cancer.

We report a case of a 74-year-old man who developed myocarditis complicated by atrioventricular (AV) block following two doses of nivolumab for the treatment of non-small cell lung cancer. A diagnosis of drug-induced acute myocarditis with complete AV block was considered on the basis of elevated troponin, new onset left ventricular (LV) systolic dysfunction, absence of acute myocardial infarction and some findings suggestive of myocarditis on cardiac magnetic resonance. The patient was commenced on glucocorticoids, perindopril and carvedilol. AV block and LV dysfunction persisted despite 2 weeks of treatment. He ultimately became hypotensive which prompted an implantation of a cardiac resynchronisation therapy pacemaker. Follow-up echocardiogram at 6 weeks showed resolution of LV systolic dysfunction. However, he continued to have AV block.

Alkalis and Skin.

The aim of this editorial is to provide an overview of the chemical interactions occurring in the skin of our patients on contact with alkaline agents. Strongly basic alkali is highly aggressive and will readily hydrolyze (or cleave) key biological molecules such as lipids and proteins. This phenomenon is known as saponification in the case of lipids and liquefactive denaturation for peptides and proteins. A short section on current first-aid concepts is included. A better understanding of the basic science behind alkali burns will make us better teachers and provide an insight into the urgency needed in treating these common and dangerous chemical injuries.