This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

Objective:To explore whether the muscarinic acetylcholine receptor M1(M1 AChR)regulate the expression of ionotropic glutamate receptor AMP A type subunit 1(GluA1)and ionotropic glutamate receptor AMP A type subunit 2(GluA2),thus participating in the effects of plateau hypoxia on learning and memory in rats.Methods:Rats were randomly divided into normoxic group(Control),plateau hypoxia group(Hypoxia)and plateau hypoxia+TAK-071(an agonist of M1AChR)group.Morris water maze was utilized to detect the learning and memory ability of rats.Immunohistochemistry was utilized to determine the distribution and expression levels of M1 AChR,GluA1,and GluA2 in hippocampal CA1 and CA3 areas of rats.Western Blot was utilized to determine the expression levels of M1 AChR,GluA1,p-GluA1(Ser845),GluA2 and p-GluA2(Ser880)in hippocampus of rats.RT-qPCR was utilized to determine the mRNA expression levels of M1 AChR,GluA1,GluA2,ionotropic glutamate receptor NMDA type subunit 2A(NR2A),tau and amyloid β-protein(Aβ)in hippocampus of rats.Results:Plateau hypoxia could significantly increase the escape latency of rats in the spatial navigation test and shorten the stay time of rats in the target quadrant in the spatial probe test,while TAK-071 treatment could significantly improve the memory status of rats damaged by plateau hypoxia in the spatial probe test.There was a good correlation between the expression of GluA1,GluA2 and M1 AChR in CA1 and CA3 regions of hippocampus.In hippocampus,the expressions of GluA1 and GluA2 were synchro-nized with their corresponding phosphorylated proteins,and the correlativity between GluA1 and GluA2 and M1 AChR changed due to plateau hypoxia was reversed after TAK-071 treatment.TAK-071 could significantly reduce(P＜0.05)the expression levels of M1 AChR,GluA1,GluA2,NR2A,tau and Aβ mRNA increased due to plateau hypoxia.Conclusion:Activating M1 AChR can improve the memory impairment of rats caused by plateau hypoxia by regulating the expression of GluA1,GluA2 and their phosphorylated proteins.

Objective:To explore whether the muscarinic acetylcholine receptor M1(M1 AChR)regulate the expression of ionotropic glutamate receptor AMP A type subunit 1(GluA1)and ionotropic glutamate receptor AMP A type subunit 2(GluA2),thus participating in the effects of plateau hypoxia on learning and memory in rats.Methods:Rats were randomly divided into normoxic group(Control),plateau hypoxia group(Hypoxia)and plateau hypoxia+TAK-071(an agonist of M1AChR)group.Morris water maze was utilized to detect the learning and memory ability of rats.Immunohistochemistry was utilized to determine the distribution and expression levels of M1 AChR,GluA1,and GluA2 in hippocampal CA1 and CA3 areas of rats.Western Blot was utilized to determine the expression levels of M1 AChR,GluA1,p-GluA1(Ser845),GluA2 and p-GluA2(Ser880)in hippocampus of rats.RT-qPCR was utilized to determine the mRNA expression levels of M1 AChR,GluA1,GluA2,ionotropic glutamate receptor NMDA type subunit 2A(NR2A),tau and amyloid β-protein(Aβ)in hippocampus of rats.Results:Plateau hypoxia could significantly increase the escape latency of rats in the spatial navigation test and shorten the stay time of rats in the target quadrant in the spatial probe test,while TAK-071 treatment could significantly improve the memory status of rats damaged by plateau hypoxia in the spatial probe test.There was a good correlation between the expression of GluA1,GluA2 and M1 AChR in CA1 and CA3 regions of hippocampus.In hippocampus,the expressions of GluA1 and GluA2 were synchro-nized with their corresponding phosphorylated proteins,and the correlativity between GluA1 and GluA2 and M1 AChR changed due to plateau hypoxia was reversed after TAK-071 treatment.TAK-071 could significantly reduce(P＜0.05)the expression levels of M1 AChR,GluA1,GluA2,NR2A,tau and Aβ mRNA increased due to plateau hypoxia.Conclusion:Activating M1 AChR can improve the memory impairment of rats caused by plateau hypoxia by regulating the expression of GluA1,GluA2 and their phosphorylated proteins.

BACKGROUND: Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network. METHODS: A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve. RESULTS: An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00. CONCLUSION: Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging. TRIAL REGISTRATION chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.
Artificial Intelligence ; Humans ; Magnetic Resonance Imaging ; Neoplasm Staging ; Neural Networks, Computer ; Rectal Neoplasms/pathology* ; Retrospective Studies

Lycophytes and seed plants constitute the typical vascular plants. Lycophytes have been thought to have no paleo-polyploidization although the event is known to be critical for the fast expansion of seed plants. Here, genomic analyses including the homologous gene dot plot analysis detected multiple paleo-polyploidization events, with one occurring approximately 13-15 million years ago (MYA) and another about 125-142 MYA, during the evolution of the genome of Selaginella moellendorffii, a model lycophyte. In addition, comparative analysis of reconstructed ancestral genomes of lycophytes and angiosperms suggested that lycophytes were affected by more paleo-polyploidization events than seed plants. Results from the present genomic analyses indicate that paleo-polyploidization has contributed to the successful establishment of both lineages-lycophytes and seed plants-of vascular plants.
Evolution, Molecular ; Genome, Plant ; Genomics ; Phylogeny ; Polyploidy ; Selaginellaceae/genetics*

Acquired Immunodeficiency Syndrome ; epidemiology ; Adult ; China ; epidemiology ; Cross-Sectional Studies ; Female ; HIV Infections ; epidemiology ; Humans ; Middle Aged ; Poverty Areas ; Young Adult

ObjectiveTo investigate the epidemic situation of brucellosis in Datong city, and to provide scientific evidence for making appropriate prevention and control measures. MethodsSurveillance data of human brucellosis in 7 countris and 4 districts in Datong city between 2006 and 2009 were collected, throng the national network straight quote system in an infectious diseases. Excel database was established and all data were statistically analyzed. Incidence of brucellosis in local population was analyzed. The regional distribution, time distribution,occupation, age and sex distribution were analyzed. Epidemic characteristics and trend of brucellosis in Datong city were summarized. Results A total of 5195 cases of brucellosis patients in Datong were found between 2006 and 2009, the average incidence rate was 57.51/10 million. All counties had the disease, and the onset of the disease mainly in the spring and summer. Most cases were young males. Farmer case was 81.67％(4243/5195) of the total patients. ConclusionsFrom 2006 to 2009, epidemic characteristic of Datong human brucellosis ishigh-low-high(incidence). We suggests the Department concerned to strengthen the prevention and control of the disease in some counties, focusing on spreading of disease prevention and control knowledge among farmers and increase their self-protection awareness.

Objective To evaluate the efficacy and toxicity of SMILE regimen for NK/T-cell lymphoma. Methods From November 2006 to February 2008, 5 patients with relapsed and 5 with first treatment NK/T-cell lymphoma were involved in this study. These patients were treated with SMILE regimen including methotrexate, isofosfamide, L-asparaginase and etoposide.1 patient were treated with autolognus hematopoietic stem cell transplantation (AHSCT), and 2 patients received local regional radiation following SMILE. Results Among 10 patients, 8 were eligible to response evaluation. The overall response rate for whole group was 50 %(4/8) without complete remission. The overall response rate for both previously untreated and relapsed patients were 50 %(2/4). Major toxicity were bone marrow supression and transient transaminase elevation, the incidence of grade Ⅲ -Ⅳ neutroponia was 65 %, and febrile neutropenia was 25 %, Grade Ⅲ transaminase elevation was 10 %. Other toxicities were mild, no treatment-related mortality occurred. 26.1% cycles discontinued due to severe side effect. Conclusion SMILE may be an effective regimen for relapsed or refractory NK/T-cell lymphoma while significant toxicities were observed. Further investigation is requried before SMILE become a standard combination for relapsed or refractory NK/T-cell lymphoma.