A Metabonomics Profiling Study on Phlegm Syndrome and Blood-Stasis Syndrome in Coronary Heart Disease Patients Using Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

A metabonomics approach based on liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) was utilized to obtain potential biomarkers of coronary heart disease (CHD) patients and investigate the ZHENG types differentiation in CHD patients. The plasma samples of 20 CHD patients with phlegm syndrome, 20 CHD patients with blood-stasis syndrome, and 16 healthy volunteers were collected in the study. 26 potential biomarkers were identified in the plasma of CHD patients and 19 differential metabolites contributed to the discrimination of phlegm syndrome and blood-stasis syndrome in CHD patients (VIP>1.5; P<0.05) which mainly involved purine metabolism, pyrimidine metabolism, amino acid metabolism, steroid biosynthesis, and arachidonic acid metabolism. This study demonstrated that metabonomics approach based on LC-MS was useful for studying pathologic changes of CHD patients and interpreting the differentiation of ZHENG types (phlegm and blood-stasis syndrome) in traditional Chinese medicine (TCM)

Ethnopharmacokinetic- and Activity-Guided Isolation of a New Antidepressive Compound from Fructus Aurantii Found in the Traditional Chinese Medicine Chaihu-Shugan-San: A New Approach and Its Application

Aims. We aimed to identify an antidepressive compound found in traditional Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and activity-guided isolation (EAGI). Methods. The new approach targets an unknown chromatographic peak produced by an absorbed compound found in oral Chaihu-Shugan-San (CSS) taken by patients with depression. Once the compound was isolated from Fructus Aurantii (FA), spectral data was employed to identify the compound. The effects of this compound, FA, and CSS on depressive behaviors were investigated. Results. The identified compound was merazin hydrate (MH) according to the new approach. MH, FA, and CSS significantly reduced immobility time and increased locomotor activity. The effects of MH, FA and CSS were similar to Fluoxetine at high doses. Conclusion. MH, a compound whose antidepressive effect is similar to FA and CSS, was isolated for the first time from FA via targeting its corresponding unknown chromatographic peak, and its antidepressive effect was compared with FA or CSS. These findings highlight the potential for drug R&D and pharmacological research of ∼100,000 TCMs

Diagnosis and segmentation effect of the ME-NBI-based deep learning model on gastric neoplasms in patients with suspected superficial lesions - a multicenter study

BackgroundEndoscopically visible gastric neoplastic lesions (GNLs), including early gastric cancer and intraepithelial neoplasia, should be accurately diagnosed and promptly treated. However, a high rate of missed diagnosis of GNLs contributes to the potential risk of the progression of gastric cancer. The aim of this study was to develop a deep learning-based computer-aided diagnosis (CAD) system for the diagnosis and segmentation of GNLs under magnifying endoscopy with narrow-band imaging (ME-NBI) in patients with suspected superficial lesions.MethodsME-NBI images of patients with GNLs in two centers were retrospectively analysed. Two convolutional neural network (CNN) modules were developed and trained on these images. CNN1 was trained to diagnose GNLs, and CNN2 was trained for segmentation. An additional internal test set and an external test set from another center were used to evaluate the diagnosis and segmentation performance.ResultsCNN1 showed a diagnostic performance with an accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 90.8%, 92.5%, 89.0%, 89.4% and 92.2%, respectively, and an area under the curve (AUC) of 0.928 in the internal test set. With CNN1 assistance, all endoscopists had a higher accuracy than for an independent diagnosis. The average intersection over union (IOU) between CNN2 and the ground truth was 0.5837, with a precision, recall and the Dice coefficient of 0.776, 0.983 and 0.867, respectively.ConclusionsThis CAD system can be used as an auxiliary tool to diagnose and segment GNLs, assisting endoscopists in more accurately diagnosing GNLs and delineating their extent to improve the positive rate of lesion biopsy and ensure the integrity of endoscopic resection

Winter Green Manure Decreases Subsoil Nitrate Accumulation and Increases N Use Efficiencies of Maize Production in North China Plain

Planting a deep-rooted green manure (GM) (more than 1.0 m depth) greatly improves soil fertility and reduces the loss of nutrients. However, few studies have examined the response of soil nitrogen (N) distribution in the soil profile and subsoil N recovery to the long-term planting and incorporation of deep-rooted GM. Based on a 12-year (2009–2021) experiment of spring maize-winter GMs rotation in the North China Plain (NCP), this study investigated the effects of different GMs that were planted over the winter, including ryegrass (RrG, Lolium L.) (>1.0 m), Orychophragmus violaceus (OrV, Orychophragmus violaceus L.) (>0.8 m), and hairy vetch (VvR, Vicia villosa Roth.) (>1.0 m), on the spring maize yield, N distribution in the deep soil profile, N use efficiencies, functional gene abundances involving soil nitrification–denitrification processes and N2O production. Compared with the winter fallow, the maize yield significantly increased by 11.6% after 10 years of green manuring, and water storage in 0–200 cm soil profile significantly increased by 5.0–17.1% at maize seedling stage. The total N content in the soil layer at 0–90 cm increased by 15.8–19.7%, while the nitrate content in the deep soil layer (80–120 cm) decreased by 17.8–39.6%. Planting GM significantly increased the N recovery rate (10.4–32.7%) and fertilizer N partial productivity (4.6–13.3%). Additionally, the topsoil N functional genes (ammonia-oxidizing archaea amoA, ammonia-oxidizing bacterial amoA, nirS, nirK) significantly decreased without increasing N2O production potential. These results indicated that long-term planting of the deep-rooted GM effectively reduce the accumulation of nitrates in the deep soil and improve the crop yield and N use efficiencies, demonstrating a great value in green manuring to improve the fertility of the soil, increase the crop yield, and reduce the risk of N loss in NCP

Mechanistic study of the radical SAM-dependent amine dehydrogenation reactions

The radical SAM enzyme NosL catalyzes the conversion of L-Trp to 3-methyl-2-indolic acid, and this reaction is initiated by the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction from the L-Trp amino group. We demonstrate here that when D-Trp was used in the NosL reaction, hydrogen abstraction occurs promiscuously at both the amino group and C alpha of D-Trp. These results inspired us to establish the detailed mechanism of L-Trp amine dehydrogenation catalyzed by a NosL mutant, and to engineer a novel radical SAM-dependent L-Tyr amine dehydrogenase from the thiamine biosynthesis enzyme ThiH

Effect of optic disk-fovea distance on measurements of individual macular intraretinal layers in normal subjects

Purpose: To investigate the effect of optic disk-fovea distance (DFD) on measurements of macular intraretinal layers using spectral domain optical coherence tomography in normal subjects. Methods: One hundred and eighty-two eyes from 182 normal subjects were imaged using spectral domain optical coherence tomography. The average thicknesses of eight macular intraretinal layers were measured using an automatic segmentation algorithm. Partial correlation test and multiple regression analysis were used to determine the effect of DFD on thicknesses of intraretinal layers. Results: Disk-fovea distance correlated negatively with the overall average thickness in all the intraretinal layers (r Conclusion: Thinner measurements of macular intraretinal layers were significantly associated with greater DFD. A clinical assessment of macular intraretinal layers in the evaluation of various macular diseases should always be interpreted in the context of DFD

Development of an Ultra-High Performance Liquid Chromatography Method for Simultaneous Determination of Six Active Compounds in Fructus aurantii and Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Rats Administered with Different Doses

A rapid, accurate, and sensitive ultra-high performance liquid chromatography (UHPLC) method was established for simultaneously detecting naringin, hesperidin, neohesperidin, meranzin hydrate, naringenin, and hesperetin in Fructus aurantii (FA) decoction. Analysis was performed on Waters BEH (R) C18 (50 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.2 mL/min by using (A) acetonitrile and (B) 0.5% acetic acid-water as the mobile phase. The method was well validated on linearity, precision, recoveries, and stability. Then, we used the same UHPLC conditions for quantitative analysis of meranzin hydrate, naringenin, and hesperetin in rat plasma. The method proved to be linear within the concentration ranges of 3.3–3300 ng/mL for meranzin hydrate, 6.95–3555 ng/mL for naringenin, and 1.8–236 ng/mL for hesperetin. The RSD of precision ranged from 1.22% to 9.08%, and the average extraction recovery ranged from 96.49 ± 1.42% to 102.01 ± 3.16%. Besides, we performed a comparative pharmacokinetic study after oral administration of FA decoction at a low dose of 15 g/kg and high dose of 30 g/kg body weight for seven days to rats. The AUC(0–t) and Cmax of meranzin hydrate, naringenin, and hesperetin were multiplied significantly with the increase of FA dosage, and the t1/2 of meranzin hydrate was faster than naringenin and hesperetin in the two groups

Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

Background. Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective. This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods. The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results. Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p<0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p<0.05). Besides, the high-dose CSS combined with the fluoxetine group was significantly better than the fluoxetine group and CSS group (p<0.05). Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation