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

Stathmin 1 (STMN1) is a microtubule-binding cytoplasmic phosphoprotein that promotes microtubule depolymerization or inhibits microtubule assembly, thereby regulating cytoskeletal organization and cell cycle progression. STMN1 is upregulated in a variety of malignant tumors, where it drives proliferation, invasion, metastasis, and angiogenesis through classic pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and ferroptosis. STMN1 can also modulate the function of immune cells, thereby influencing antitumor immunity. Clinical data show that its high expression correlates positively with tumor drug resistance and poor prognosis, suggesting that STMN1 has potential as a tumor biomarker and therapeutic molecular target with important clinical significance.
Humans ; Stathmin/metabolism* ; Neoplasms/genetics* ; Biomarkers, Tumor/metabolism* ; NF-kappa B/metabolism* ; Cell Proliferation ; Drug Resistance, Neoplasm

Objective To develop a GIS-based 3D playback system for the flight human-plane data to realize the fusion of pilots'airborne flight data and physiological data.Methods The 3D playback system was developed with the Browser/Server(B/S)architecture,micro-server model,Java language and Spring Cloud technology framework,which was composed of three functional modules for flight process reproduction,physiological situational awareness and critical event calibration analysis.Results The system developed achieved time synchronization and data fusion of airborne flight data and physiological data with a time synchronization frequency of 1 Hz and a refresh rate of not less than 120 frames/s.Conclusion The system developed with high safety,stability,reliability and accuracy facilitates pilot in-flight physiological monitoring and fusion and simultaneous display of airborne flight data and physiological data,which can be used as an important platform for decision-making support in flight training.[Chinese Medical Equipment Journal,2024,45(10):14-19]

Metabolic associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease worldwide because of lifestyle and dietary changes. Gut microbiota and its metabolites have been shown to play a critical role in the pathogenesis of MAFLD. Understanding of the function of gut microbiota and its metabolites in MAFLD may help to elucidate pathological mechanisms, identify diagnostic markers, and develop drugs or probiotics for the treatment of MAFLD. Here we review the pathogenesis of MAFLD by gut microbiota and its metabolites and discuss the feasibility of treating MAFLD from the perspective of gut microbes.
Gastrointestinal Microbiome ; Fatty Liver/microbiology* ; Humans

Objective:To explore the association between the G71R polymorphism of the UGT1A1 gene and neonatal hyperbilirubinemia. Methods:DNA was extracted from blood samples of 61 neonates with severe neonatal hyperbilirubinemia(severe neonatal hyperbilirubinemia group), 60 neonates with hyperbilirubinemia(hyperbilirubinemia group) and 62 healthy neonates(control group), the G71R mutation of UGT1A1 gene was analyzed by direct sequencing. Results:In severe neonatal hyperbilirubinemia group, there were 17 cases of homozygous mutation(A/A), 23 cases of heterozygous mutation(A/G) , and 21 cases of wild type(G/G) , with 28.87% homozygous mutation rate and 37.70% heterozygous mutation rate.In neonatal hyperbilirubinemia group, there were ten cases of homozygous mutation(A/A), 28 cases of heterozygous mutation(A/G) and 22 cases of wild type(G/G), with 16.67% homozygous mutation rate and 46.67% heterozygous mutation rate.In the control group, there were nine cases of homozygous mutation (A/A), 28 cases of heterozygous mutation(A/G) and 25 cases of wild type(G/G), among which the homozygous mutation rate was 14.52% and the heterozygous mutation rate was 45.16%.The genotype frequency( χ2=4.14, P=0.38)and allele frequency( χ2=2.47, P=0.29)of G71R in severe neonatal hyperbilirubinemia group, neonatal hyperbilirubinemia group and control group were not statistically significant. Conclusion:The G71R polymorphism of the UGT1A1 gene may not be significantly correlated with the prevalence of neonatal hyperbilirubinemia.

OBJECTIVE To establi sh the fingerprint of Cnidium monnieri and a method for the content determination of 4 kinds of coumarins. METHODS Ultra-high performance liquid chromatography （UPLC） method was adopted to establish the fingerprints of 21 batches of C. monnieri ； their similarities were evaluated with Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）；common peaks were identification by comparison with reference substance. Using 10 common peak areas as variables ，cluster analysis was performed for 21 batches of C. monnieri by the method of between groups. The relative correction factors of xanthotoxin ，bergapten and imperatorin were calculated by the same UPLC method with osthole as the internal reference. The contents of them were calculated by quantitative analysis of multi-components by single marker （QAMS），and compared with the results of external standard method. RESULTS Totally 10 common peaks were identified in the fingerprints of 21 batches of C. monnieri ；the similarities ranged from 0.997 to 1.000. Peak 4 was identified as xanthotoxin ，peak 8 as bergapten ，peak 9 as imperatorin and peak 10 as osthole. A total of 21 batches of samples were divided into 3 categories，of which S 7 was clustered into one category ，S14 was clustered into one category ，and the other 19 batches were clustered into one category. The relative deviations of the contents of xanthotoxin ，bergapten and imperatorin determined by QAMS and external standard method were in the range of 0.88％ -1.07％ ，2.22％ -2.29％ ，0.67％ -2.93％ ，respectively. CONCLUSIONS UPLC fingerprint of C. monnieri is successfully established ，and QAMS method for content determination of 4 coumarins is also established.

OBJECTIVE: To investigate the function of RAS protein on the progression of the T-ALL cell lines in vitro. METHODS: The DNA of the T-ALL cells was purified then amplified the coding regions of three RAS genes (KRAS, NRAS, HRAS) by PCR reaction. After T-A cloning, the coding regions of KRAS, NRAS and HRAS were sequenced by Sanger Sequencing. The siRNA oligonucleotides were cloned into the pSEH-361 vector, which were then packaged into retroviral together with pAMPHO and pVSVG in the HEK-293T cells. The T-ALL cells were infected with the retrovirus. The gene expressions were detected by qRT-PCR and Western blot. The T-ALL cells were stained with Annexin V-PE/7-AAD and the apoptotic cells were detected by flow cytometry. The T-ALL cells were stained with Hoechst 33258, and the cell cycle distribution was determined by flow cytometry. The expression of cleaved-Caspase 3 was stained with antibody and observed with fluorescence microscope. RESULTS: For RAS genes, beside the Loucy and the P12-ICH cells harbored KRAS c.6187G>A (p.KRAS^G12D) homozygous mutant, no missense mutation of RAS was found in other T-ALL cells genome. The pan RAS inhibitor compound 3144 showed toxicity to all tested T-ALL cells, except PEER (IC₅₀=47.916 μmol/L). Similarly, Tipifarnib induced apoptosis of multiple T-ALL cell lines except for the PEER cells (IC₅₀=94.2265 μmol/L). After KRAS knock-down, the T-ALL cells showed significant apoptosis and an arrested cell cycle. CONCLUSION The KRAS protein is vital for the progression of the T-ALL cells in vitro, it is a potential therapeutic target for T-ALL patients.
Apoptosis ; Cell Line ; Cell Proliferation ; Humans ; Mutation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Proto-Oncogene Proteins p21(ras)/genetics*

OBJECTIVE: To establish the technique that take the advantages of flow cytometry combined fluorescence in situ hybridization (Flow-FISH) to identify the Epstein-Barr virus(EBV) infected lymphocyte subtypies in patients' peripheral blood sample. METHODS: Peripheral Blood monocyte from 9 patients with EBV infection enrolled at Children's Hospital in Chongqing Medical University were isolated by Ficoll-paque centrifugal separation. The expressions of EBER1, EBER2 in cell were detected by qRT-PCR. The surface markers of cell were detected by Flow cytometry after staining with their antibodies. The cell was treated Fix-Permeabilization Buffer before hybridization with fluorescent labeled probe at 37 ℃ overnight. The cell status, surface markers and targeted mRNA are detected by flow cytometry and fluorescence microscope. RESULTS: It was optimized that the Fix-Permeabilization Buffer and recipe with 0.2% Tween-20 were picked out as providing a good cell integrity and high resolution of surface markers. Hybridization with 20% formamide and 7% dextran sulfate at 37 ℃ overnight is the optimal hybridization condition as a good hybridization effect, a detectable cell integrity and a high resolution of cell markers under flow cytometry detection. Finally, upon the established Flow-FISH method, lymphocyte subpopulations of the EBV⁺ cells from cell lines and blood samples of patients were identified successfully. CONCLUSION A Flow-FISH technology is established, which can be applied in the identification of EBV infected cell subtypes. This research provides a foundmental for its application in clinical test in EBV⁺ related proliferative diseases.
Epstein-Barr Virus Infections ; Flow Cytometry/methods* ; Herpesvirus 4, Human ; Humans ; In Situ Hybridization, Fluorescence/methods* ; Lymphocyte Subsets

Objective : To explore the effects of autophagy activation on propofol⁃induced apoptosis in hippocampal neurons. Methods : Primary hippocampal neurons were extracted and isolated from fetal rats and randomly divided into control group, propofol group, rapamycin group and chloroquine group. 2,3⁃Bis⁃(2⁃methoxy⁃4⁃nitro⁃5⁃sulfo phenyl) Ⅳ2H⁃tetrazolium⁃5⁃carboxanilide ( XTT) and flow cytometry were used to detect apoptosis, and Western blot was used to detect the expression of autophagy and apoptosis⁃related proteins. Then, aged rats were randomly divided into control group, propofol group, rapamycin group and chloroquine group. 100 mg/kg propofol was used for continuous anesthesia for 1 week, during which 50 mg/kg rapamycin and 10 mg/kg chloroquine were treated. Morris water maze was used to detect cognitive function, TUNEL staining was used to detect apoptosis, Golgi staining was used to observe autophagy, and Western blot was used to detect autophagy⁃related apoptosis⁃related protein expression. Results : In vitro, rapamycin obviously reversed the apoptosis caused by propofol, but chloroquine had no effect. Compared with propofol group, the expression of microtubule⁃associated protein light chain 3 Ⅱ / microtubule⁃associated protein light chain 3 I (LC3 Ⅱ/LC3 Ⅰ) and Beclin⁃1 in the rapamycin group increased, but the expression of apoptotic proteins Cleaved⁃caspase⁃3 and Bax decreased. In vivo, compared with propofol group, the water maze escape latency of the rapamycin group reduced. In addition, the number of TUNEL⁃positive cells and autophagosomes in the rapamycin group decreased. Furthermore, the expression of mammalian target of rapamycin (mTOR) in the rapamycin group decreased, and the expression of LC3 Ⅱ/LC3 Ⅰ and Beclin⁃1 increased, as well as the expression of Cleaved⁃caspase⁃3 and Bax decreased. But chloroquine had no effect on autophagy and apoptosis⁃related proteins. Conclusion Rapamycin can further activate autophagy by inhibiting the activation of mTOR signal, ameliorate the neuronal apoptosis caused by propofol, which will lead to the improvement of the cognition in rats.

OBJECTIVE: To observe the therapeutic effect of horizontal penetration needling combined with rizatriptan monobenzoate tablets, simple horizontal penetration needling and simple rizatriptan monobenzoate tablets for migraine without aura in acute stage. METHODS: A total of 99 patients with migraine without aura in acute stage were randomized into an acupuncture plus medication group, an acupuncture group and a western medication group, 33 cases in each one. In the acupuncture group, horizontal penetration needling was applied once at Hanyan (GB 4) to Xuanli(GB 6), Shenting (GV 24) to Yintang (GV 29), Baihui (GV 20) to Qianding (GV 21), etc. for 2 h. In the western medication group, oral rizatriptan monobenzoate tablets for 10 mg were given once. In the acupuncture plus medication group, treatment of acupuncture combined with rizatriptan monobenzoate tablets were given, the application was the same as the acupuncture group and the western medication group. Before treatment and 0.5, 2, 24 h after treatment, the visual analogue scale (VAS) score was observed, the remission rate and the disappearance rate of migraine of 2, 24 h after treatment were compared in the 3 groups. RESULTS: Compared before treatment, the VAS scores of each time point after treatment were decreased in the 3 groups ( CONCLUSION Horizontal penetration needling combined with rizatriptan monobenzoate tablets have significant therapeutic effect on rapid analgesia and continuous analgesia for migraine without aura in acute stage, its effect is superior to simple horizontal penetration needling and simple rizatriptan monobenzoate tablets.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Migraine without Aura ; Tablets ; Treatment Outcome ; Triazoles ; Tryptamines