This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

In clinical practice, antibiotics have historically been utilized for the treatment of pathogenic bacteria. However, the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach. In 2022, Escherichia coli, a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence, emerged as the predominant pathogenic bacterium in China. The rapid emergence of antibiotic-resistant E. coli strains has rendered antibiotics insufficient to fight E. coli infections. Traditional Chinese medicine (TCM) has made remarkable contributions to the health of Chinese people for thousands of years, and its significant therapeutic effects have been proven in clinical practice. In this paper, we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E. coli infections. First of all, this review introduces the classification, antibiotic resistance characteristics and mechanisms of E. coli. Then, the TCM formulas and extracts are listed along with their active ingredients against E. coli, including extraction solution, minimum inhibitory concentration (MIC), and the antibacterial mechanisms. In addition, there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E. coli infections, and we provide a summary of this evidence and its underlying mechanisms. In conclusion, we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E. coli infections. We hold the opinion that TCM will play an important role in global health, pharmaceutical development, and livestock farming in the future.

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Objective This study explores the efficacy and underlying mechanisms of combining rhCYGB with 5-FU to target hypoxia-induced treatment resistance in liver cancer.The aim is to develop a novel combinato-rial therapy strategy for improving outcomes in patients with refractory liver cancer.Methods The half-maximal inhibitory concentration(IC50)of drugs on liver cancer cells under normoxia and hypoxia was determined,and dose-response curves were generated to assess sensitivity to 5-FU.The combined effects of rhCYGB and 5-FU were analyzed withCompuSyn and SynergyFinder 3.0.Tumor stem cell sphere formation assays and flow cytometry for CD133-positive cells were conducted to evaluate the impact on cancer stemness.Wound healing assays assessed the effects on migration.Results The IC50 values under hypoxia exhibited a significant fold change compared to normoxia(P<0.05),specifically a 15.27-fold,4.25-fold,and 2.34-fold increase for Hep3B,Huh7,and HepG2 cells respectively.Assessment of drug combination effects demonstrated a synergistic interaction between 5-FU and rhCYGB.Compared to the 5-FU monotherapy group,the combination of 5-FU and rhCYGB exerted an inhibitory effect on the formation of liver cancer stem cell spheres(P<0.05)and significantly downregulated the proportion of CD133-positive subpopulations in Hep3B cells(P<0.05).Wound healing assay results revealed a synergistic inhibitory effect on the migration of Hep3B cells after 48 hours of treatment with rhCYGB combined with 5-FU undernormoxia(P<0.05).Conclusions The combination of rhCYGB and 5-FU demonstrates syner-gistic effects in liver cancer.The underlying mechanism may involve the modulation of stemness and cell migration capacity.

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

OBJECTIVE To prepare zeolite imidazole framework （ZIF）-8 nanoparticles （NPs） loaded with temozolomide （TMZ） （abbreviated as TMZ@ZIF-8 NPs） drug delivery system， thus increasing drug enrichment and anti-glioma effects in lesions. METHODS After preparing ZIF-8 NPs using the room temperature solution reaction method， the impregnation method was used to prepare TMZ@ZIF-8 NPs drug delivery system. Characterization was carried out using transmission electron microscopy， laser particle size， and Fourier transform infrared spectroscopy， and dissolution and anti-tumor activity experiments in vitro and in vivo were conducted. RESULTS TMZ@ZIF-8 NPs were successfully prepared with the particle size of （126.23±7.92） nm， drug loading amount of （28.79±1.26）%， and 72 h cumulative dissolution rate of （72.36±3.62）%. The results of in vitro anti-tumor activity experiments showed that the relative cell survival rate of ZIF-8 NPs remained above 90%； the prepared TMZ@ZIF-8 NPs delivery system exhibited superior inhibition， higher uptake capacity， and better promoting apoptosis effects on the growth and proliferation of C6 cells as compared with the free TMZ. The results of in vivo anti-tumor activity experiments showed that ZIF-8 NPs were not enriched in the brain of rats， and the enrichment effect of TMZ in the brain was not significant， while TMZ@ZIF-8 NPs had a significant enrichment effect in the brain. CONCLUSIONS ZIF-8 NPs can effectively load TMZ， and successfully prepared TMZ@ZIF-8 NPs can improve TMZ uptake ability and anti-glioma effect.

The tumor microenvironment includes blood vessels， lymph， nerves， non-malignant cells， and their metabolites at and near the tumor lesion site， which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption， or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply， forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors， widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer， occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets， the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer， inhibit the proliferation， invasion， and metastasis of breast cancer cells in the hypoxia environment， induce apoptosis， reverse their drug resistance， intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment， and inhibit their angiogenesis， thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation， invasion， metastasis， drug resistance， immune function， metabolic reprogramming， non-coding RNA， iron death， and autophagy of breast cancer cells， which affected the occurrence and development of breast cancer， and it elaborated the mechanism behind it. Then， the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine， so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.

OBJECTIVE To explore the neural mechanisms underlying the speech perception in individuals with normal hearing under the influence of selective attention.METHODS There were 32 individuals with normal hearing who were recruited.By manipulating the participants'selective attention,two simultaneous speech streams were differentiated into target and interfering speech.Participants were guided to complete an auditory perception electroencephalogram(EEG)experiment.Fourier spectrum analysis was used to calculate the spectrum responses induced by the two types of speech,and the differences in EEG energy values at the levels of character,word,and phrase were compared.RESULTS This study observed significant differences in the EEG responses between target and ignored speech at the word level(2 Hz),while no significant differences were observed at the character level(4 Hz)and phrase level(1 Hz).CONCLUSION In environments with multiple speech streams,selective attention primarily processes and encodes the interested speech at the word level rapidly and effectively.This study preliminarily reveals how the brain represents auditory language and constructs different language hierarchy units under the modulation of selective attention,providing a theoretical model for hearing aid algorithms in hearing-impaired patients.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*