Untargeted Metabolomics and Physicochemical Analysis Revealed the Quality Formation Mechanism in Fermented Milk Inoculated with Lactobacillus brevis and Kluyveromyces marxianus Isolated from Traditional Fermented Milk.

Traditional fermented milk from the western Sichuan plateau of China has a unique flavor and rich microbial diversity. This study explored the quality formation mechanism in fermented milk inoculated with Lactobacillus brevis NZ4 and Kluyveromyces marxianus SY11 (MFM), the dominant microorganisms isolated from traditional dairy products in western nan. The results indicated that MFM displayed better overall quality than the milk fermented with L. brevis NZ4 (LFM) and K. marxianus SY11 (KFM), respectively. MFM exhibited good sensory quality, more organic acid types, more free amino acids and esters, and moderate acidity and ethanol concentrations. Non-targeted metabolomics showed a total of 885 metabolites annotated in the samples, representing 204 differential metabolites between MFM and LFM and 163 between MFM and KFM. MFM displayed higher levels of N-acetyl-L-glutamic acid, cysteinyl serine, glaucarubin, and other substances. The differential metabolites were mainly enriched in pathways such as glycerophospholipid metabolism, arginine biosynthesis, and beta-alanine metabolism. This study speculated that L. brevis affected K. marxianus growth via its metabolites, while the mixed fermentation of these strains significantly changed the metabolism pathway of flavor-related substances, especially glycerophospholipid metabolism. Furthermore, mixed fermentation modified the flavor and quality of fermented milk by affecting cell growth and metabolic pathways.

Targeted Perioperative Nursing Combined with Propofol and Fentanyl for Gynecological Laparoscopic Surgery.

Objective: The aim of this study is to investigate the clinical effects of targeted perioperative nursing combined with propofol and fentanyl in gynecological laparoscopic surgery. Methods: Patients who were admitted to our hospital for gynecological laparoscopic surgeries from October 1, 2019 to November 30, 2021 were included in this retrospective study. Patients in group A received routine propofol and fentanyl. Patients in group B received targeted perioperative nursing on the basis of interventions in group A. The anesthetic effects, clinical indicators, mental health status, and adverse reactions were compared between the two groups. Results: A total of 84 qualified patients were retrieved. The total effective anesthesia rate, extubation time, operation time, consciousness recovery time, intraoperative blood loss, hospital stay, SAS score, SDS score, health status indicators, and adverse events in group B were all significantly better than those in group A (P < 0.05 for all comparisons). Conclusion: Combined intervention (propofol + fentanyl + targeted perioperative care) for gynecological laparoscopic surgery patients has a significant anesthesia effect, which can effectively improve the patient's clinical indicators and mental health status and can also reduce the occurrence of adverse events. It has good safety and can be widely used in clinical practice.

The traditional uses, phytochemistry, pharmacology and toxicology of Dictamnus dasycarpus: a review.

OBJECTIVES: Dictamnus dasycarpus is a plant of the Rutaceae family, and its root bark is the main part used as a medicine, named 'Bai-Xian-Pi'. It is used to clear away heat, remove dampness, and dispel wind and also used for detoxification. The purpose of this review is to provide a systematic review about the botany, traditional uses, phytochemistry, pharmacology and toxicology of this plant. KEY FINDINGS: More than 200 compounds have been isolated and identified from the plant, including alkaloids and their glycosides, terpenoids and their derivatives and phenylpropanoids. Extensive pharmacological activities of the extracts or compounds of D. dasycarpus in vivo and in vitro were mainly confirmed, including anti-inflammatory activity, protecting cardiovascular activity, improving liver injury and anti-cancer activity. SUMMARY: In this paper, the botany, traditional uses, phytochemistry and pharmacology of D. dasycarpus were reviewed. In the future, D. dasycarpus needs further study, such as paying more attention to quality control and the utilization on agriculture. In addition, discussing the medicinal components of decoction as well as the toxicity will also contribute to the progress of clinical trial studies.

Inflammasomes and Fibrosis.

Fibrosis is the final common pathway of inflammatory diseases in various organs. The inflammasomes play an important role in the progression of fibrosis as innate immune receptors. There are four main members of the inflammasomes, such as NOD-like receptor protein 1 (NLRP1), NOD-like receptor protein 3 (NLRP3), NOD-like receptor C4 (NLRC4), and absent in melanoma 2 (AIM2), among which NLRP3 inflammasome is the most studied. NLRP3 inflammasome is typically composed of NLRP3, ASC and pro-caspase-1. The activation of inflammasome involves both "classical" and "non-classical" pathways and the former pathway is better understood. The "classical" activation pathway of inflammasome is that the backbone protein is activated by endogenous/exogenous stimulation, leading to inflammasome assembly. After the formation of "classic" inflammasome, pro-caspase-1 could self-activate. Caspase-1 cleaves cytokine precursors into mature cytokines, which are secreted extracellularly. At present, the "non-classical" activation pathway of inflammasome has not formed a unified model for activation process. This article reviews the role of NLRP1, NLRP3, NLRC4, AIM2 inflammasome, Caspase-1, IL-1ß, IL-18 and IL-33 in the fibrogenesis.

Morphology parameters for rupture in middle cerebral artery mirror aneurysms.

OBJECTIVE: To identify the morphological parameters correlated with the rupture of middle cerebral artery (MCA) aneurysms. METHODS: We retrospectively analyzed the digital subtraction angiography (DSA) data of 48 patients with ruptured mirror MCA aneurysms. Morphological parameters included aneurysm with wall protrusion, maximum diameter (Dmax), height, neck width, aneurysm width, dome projection, parent artery average diameter (Dp), aspect ratio (AR), bottleneck factor (BNF), size ratio (SR), M1/M2 ratio, and height/width (H/W) ratio. These paired parameters were analyzed by conditional univariate and multivariate logistic regressions to screen out the independent risk factors. We established a score based on the independent risk factors. Receiver operating characteristics (ROC) were generated to estimate the prediction performance of the score in our large database of 763 aneurysms. RESULTS: In the univariate regressions, Dmax, height, aneurysm width, neck width, AR, BNF, H/W ratio, SR, anterior dome projection and aneurysm with wall protrusion were significant risk factors. Aneurysm width (OR 3.296, p=0.015), AR (OR 11.594, p=0.014) and anterior dome projection (OR 9.385, p=0.016) were independent risk factors in multivariate regression. The area under the curve (AUC) value of the score based on the three independent risk factors was 0.829. CONCLUSION: Aneurysm width, AR and anterior dome projection were independent risks factors of rupture.

Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage.

Only a few types of inflammasomes have been described in central nervous system cells. Among these, the absent in melanoma 2 (AIM2) inflammasome is primarily found in neurons, is highly specific and can be activated only by double-stranded DNA. Although it has been demonstrated that the AIM2 inflammasome is activated by poly(deoxyadenylic-deoxythymidylic) acid sodium salt and leads to pyroptotic neuronal cell death, the role of AIM2 inflammasome-mediated pyroptosis in early brain injury (EBI) after subarachnoid haemorrhage (SAH) has rarely been studied. Thus, we designed this study to explore the mechanism of gasdermin D(GSDMD)-induced pyroptosis mediated by the AIM2 inflammasome in EBI after SAH. The level of AIM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The pathway of AIM2 inflammasome-mediated pyroptosis, the AIM2/Caspase-1/GSDMD pathway, was explored after experimental SAH in vivo and in primary cortical neurons stimulated by oxyhaemoglobin (oxyHb) in vitro. Then, we evaluated GSDMD-induced pyroptosis mediated by the AIM2 inflammasome in AIM2 and caspase-1- deficient mice and primary cortical neurons generated through lentivirus (LV) knockdown. Compared with that of the control samples, the AIM2 level in the CSF of the patients with SAH was significantly increased. Pyroptosis-associated proteins mediated by the AIM2 inflammasome were significantly increased in vivo and in vitro following experimentally induced SAH. After AIM2 and caspase-1 were knocked down by an LV, GSDMD-induced pyroptosis mediated by the AIM2 inflammasome was alleviated in EBI after SAH. Intriguingly, when caspase-1 was knocked down, apoptosis was significantly suppressed via impeding the activation of caspase-3. GSDMD-induced pyroptosis mediated by the AIM2 inflammasome may be involved in EBI following SAH. The inhibition of AIM2 inflammasome activation caused by knocking down AIM2 and caspase-1 alleviates GSDMD-induced pyroptosis in EBI after SAH.

Flat-detector computed tomography PBV map in the evaluation of presurgical embolization for hypervascular brain tumors.

BACKGROUND: Preoperative embolization of hypervascular brain tumors is frequently used to minimize intraoperative bleeding. OBJECTIVE: To explore the efficacy of embolization using flat-detector CT (FDCT) parenchymal blood volume (PBV) maps before and after the intervention. MATERIALS AND METHODS: Twenty-five patients with hypervascular brain tumors prospectively received pre- and postprocedural FDCT PBV scans using a biplane system under a protocol approved by the institutional research ethics committee. Semiquantitative analysis, based on region of interest measurements of the pre- and post-embolization PBV maps, operating time, and blood loss, was performed to assess the feasibility of PBV maps in detecting the perfusion deficit and to evaluate the efficacy of embolization. RESULTS: Preoperative embolization was successful in 18 patients. The relative PBV decreased significantly from 3.98±1.41 before embolization to 2.10±2.00 after embolization. Seventeen patients underwent surgical removal of tumors 24 hours after embolization. The post-embolic tumor perfusion index correlated significantly with blood loss (ρ=0.55) and operating time (ρ=0.60). CONCLUSIONS: FDCT PBV mapping is a useful method for evaluating the perfusion of hypervascular brain tumors and the efficacy of embolization. It can be used as a supplement to CT perfusion, MRI, and DSA in the evaluation of tumor embolization.

DHA-1 plasmid-mediated AmpC ß-lactamase expression and regulation of Klebsiella pnuemoniae isolates.

The present study aimed to investigate the regulatory mechanism of the AmpC enzyme by analyzing the construction and function of AmpCR, AmpE and AmpG genes in the Dhahran (DHA)­1 plasmid of Klebsiella pneumoniae (K. pneumoniae). The production of AmpC and extended­spectrum ß­lactamase (ESBL) were determined following the cefoxitin (FOX) inducing test for AmpC, preliminary screening and confirmation tests for ESBL in 10 DHA­1 plasmid AmpC enzymes of K. pneumoniae strains. AmpCR, AmpD, AmpE and AmpG sequences were analyzed by polymerase chain reaction. The pACYC184­X plasmid analysis system was established and examined by regulating the pAmpC enzyme expression. The electrophoretic bands of AmpCR, AmpD, AmpE and AmpG were expressed. Numerous mutations in AmpC + AmpR (AmpCR) and in the intergenic region cistron of AmpC­AmpR, AmpD, AmpE and AmpG were observed. The homology of AmpC and AmpR, in relation to the Morganella morganii strain, was 99%, which was determined by comparing the gene sequences of Kp1 with those of Kp17 AmpCR. The specific combination of AmpR and labeled probe demonstrated a band retarded phenomenon and established a spatial model of AmpR. All the enzyme production strains demonstrated Val93→Ala in AmpG; six transmembrane domains were found in AmpE in all strains, with the exception of Kp1 and Kp4, which had only three transmembrane segments that were caused by mutation. The DHA­1 plasmid AmpC enzymes encoded by plasmid are similar to the inducible chromosomal AmpC enzymes, which are also regulated by AmpD, AmpE, AmpR and AmpG.

Effects of probucol on angiotensin II-induced BMP-2 expression in human umbilical vein endothelial cells.

Bone morphogenetic protein-2 (BMP-2) participates significantly in vascular development and pathophysiological processes. Angiotensin II (AngII) has been demonstrated to be critical in the initiation and progression of atherosclerosis. However, the effects of AngII on BMP-2 expression and of probucol on the AngII-induced BMP-2 expression in human umbilical vein endothelial cells (HUVECs) are unknown. The aim of our study was to investigate these effects. HUVECs were cultured and stimulated with various agents. The total superoxide dismutase (SOD) activity and the concentrations of malondialdehyde (MDA) and BMP-2 were measured by standard methods. Northern blotting was used to detect the expression of BMP-2 mRNA. The activation of NF-κB in the HUVECs was also determined. The AngII treatment significantly increased BMP-2 expression levels and activated NF-κB. These effects were suppressed by treatment with pyrrolidine dithiocarbamate (PDTC) or probucol. Furthermore, the increased levels of MDA in the conditioned medium and the decrease in the total SOD activity caused by the AngII treatment were reversed by treatment with probucol or PDTC. Probucol downregulated the AngII­induced BMP-2 expression. These effects of probucol may be mediated by the inhibition of NF-κB activation.