6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

There seems to be a contradiction among the symptoms of"non-thirst"and"thirst after oral use of the decoction"stated in original text 41 of Shang Han Lun(Treatise on Febrile Diseases)and the symptom of"probable thirst"stated in original text 40.In this article,the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction were expounded through the analysis of the basic theories of traditional Chinese medicine about body fluid metabolism and the pathogenic mechanism of thirst,and by synthesizing the relevant articles recorded in Jin Gui Yao Lve(Synopsis of the Golden Chamber)and the understanding of the syndrome of Xiao Qinglong Decoction by later generations of practitioners.After that,the following views are put forward:non-thirst symptom is the primary sympton of the syndrome of Xiao Qinglong Decoction,which results from the disease;thirst after oral use of the decoction is due to drug-induced thirst,which can be classified into the category of physiological thirst;probable thirst symptom is related with fluid consumption by febrile disease,indicating that the disease involves yangming.The analysis of the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction is helpful for evaluation of therapeutic efficacy,and can also be used as the indications of modified medications and differential diagnosis of the disease.The exploration will provide references for the clinical use of Xiao Qinglong Decoction and will be beneficial to improving the clinical efficacy of Xiao Qinglong Decoction.

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To improve the efficiency of hospital antimicrobial management and ensure rational clinical use of antimicrobial agents with the aid of antimicrobial stewardship(AMS)empowered by digital intelligence tech-nology in hospital.Methods Information systems such as early warning of antimicrobial indexes,closed-loop ma-nagement of microbial detection information,and decision-making system of antimicrobial resistance monitoring data were applied to the traditional AMS system.Through hospital information systems(HIS)to collect data about thera-peutic antimicrobial use and healthcare-associated infection(HAI)quality control indexes of hospitalized patients in a tertiary first-class public hospital in Shenzhen City before and after digital technology improvement,indexes of 2021 and 2022 were as control group(before improvement)and observation group(after improvement)respective-ly,improvement trend of antimicrobial management was compared.Results After upgrading and renovating the hospital information system,hospital antimicrobial management indexes improved significantly compared to before the renovation.The use rate of antimicrobial agents and the preventive use rate of antimicrobial agents in class Ⅰincision surgery in patients in the observation group were both lower than those in the control group(27.0％vs 38.8％,20.9％vs 23.8％,respectively,both P＜0.05).Antimicrobial use density in hospitalized patients in the observa-tion group was lower than that in the control group([33.27±3.03]DDDs vs[42.06±4.42]DDDs),difference was statistically significant(t=13.11,P＜0.001).The observation group had a higher qualified rate for evaluating antimicrobial medical orders compared to the control group(98.5％vs 96.8％).The pathogenic detection rate of hospitalized patients before therapeutic antimicrobial use and pathogen detection rate related to HAI diagnosis were both higher than those in the control group(87.1％vs 84.5％,99.0％vs 95.4％,respectively),differences were both statistically significant(both P＜0.05).Conclusion Empowering the hospital's AMS system with digital technology can promote more scientific,standardized,efficient,and rational antimicrobial management in hospitals.

Objective To screen the quality evaluation indicators of Bushen Huoxue Prescription(BHP)in the treatment of diabetic retinopathy(DR)by network pharmacology and molecular docking technology,and to establish content determination of active components in BHP by ultra-high-performance liquid chromatography triple-quadrupole mass spectrometry(UHPLC-QqQ-MS/MS).Methods Network pharmacology was used to screen the disease-related targets and key components,followed by molecular docking to further verify the interaction between them and confirm the active ingredients in BHP as the quality evaluation indicators.A UHPLC-QqQ-MS/MS method for the content determination of the active ingredients in BHP was established.A ZORBAX SB-C18 column(2.1 mm×50 mm,1.8 μm)was used,and methanol(A)-0.1％formic acid solution(B)was used as mobile phase.Gradient elution was performed in multiple reaction monitor mode.The flow rate was 0.3 mL·min-1 and the injection volume was 1 μL.Results Network pharmacology and molecular docking revealed five core targets and 12 BHP-related components(verbascoside,echinacoside,isoacteoside,tanshinone ⅡA,cryptotanshinone,dihydrotanshinone I,ginsenoside Re,Rd and Rb1,puerarin,daidzin,biochanin A)for the treatment of DR.There was a strong binding affinity between them(binding energy≤-5.0 kcal·mol-1).The established quantitative method demonstrated each component presented a good linearity within the specified range(r>0.999 5).The average recovery was in the range of 97.57％～101.48％.The contents of 12 components in eight batches of BHP samples were 0.027 9％～0.050 6％,0.006 4％～0.022 0％,0.017 1％～0.041 5％,0.009 2％～0.015 4％,0.012 6％～0.020 5％,0.004 4％～0.007 6％,0.334％～0.643％,0.238％～0.530％,0.353％～0.693％,3.411％～6.048％,1.023％～1.352％,0.000 8％～0.001 8％,respectively.Conclusion Based on network pharmacology,molecular docking and UHPLC-QqQ-MS/MS,a method for rapid screening and determination of 12 active components of BHP in the prevention and treatment of DR was established.This study provided a reference for comprehensive assessment of the quality and effectiveness of BHP.

Objective:To explore the value of circ_0054633 in early diagnosis and prognosis prediction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in children with severe pneumonia.Methods:A retrospective case-control study was conducted on children with diagnosed severe pneumonia admitted to Tianjin Children's Hospital from July 1, 2022, to February 29, 2024. The clinical data was collected by electronic medical record system and clinical follow-up, including gender, age, lung injury prediction score (LIPS), pediatric critical illness score (PCIS), serum circ_0054633, interleukin-6 (IL-6), the indicators of the arterial blood-gas analysis, oxygenation index (PaO 2/FiO 2) within 24 hours of admission and the survival status of 28 days. According to whether ALI/ARDS occurred, they were divided into the ALI/ARDS group and the non-ALI/ARDS group. The differences of clinical data between the two groups were compared, and multivariate Logistic regression was used to analyze the risk factors for ALI/ARDS in children with severe pneumonia. The receiver operator characteristic curve (ROC curve) will be used to explore the early diagnostic value of ALI/ARDS in children with severe pneumonia. The patients of ALI/ARDS were divided into mild group, moderate group and severe group according to the level of PaO 2/FiO 2. The levels of serum circ_0054633 and IL-6 in various severity ALI/ARDS were compared. The differences of serum circ_0054633, IL-6 levels, PCIS score and LIPS score were compared between the two groups of ALI/ARDS patients according to different prognoses in 28 days, as well as the correlation between various risk factors and circ_0054633. Results:A total 74 children with severe pneumonia were included, with 34 cases in the ALI/ARDS group and 40 cases in the non-ALI/ARDS group. In ALI/ARDS group, there were 9 cases in the mild group, 15 cases in the moderate group and 10 cases in the severe group; while 12 cases died and 22 cases survived after 28 days. The serum circ_0054633, IL-6 level and LIPS score were higher in the ALI/ARDS group than the non-ALI/ARDS group, while the PCIS score was lower, and the two groups had significant difference. Multivariate Logistic regression analysis showed that circ_0054633 was independent predictors of ALI/ARDS in children with severe pneumonia [odds ratio ( OR) = 3.853, 95% confidence interval (95% CI) was 1.912-7.805, P = 0.017]. ROC curve analysis showed that the cut-off values for circ_0054633 in the diagnosis of ALI/ARDS were 3.955, sensitivity was 79.4%, specificity was 92.5%, area under the ROC curve (AUC) was 0.892. The serum circ_0054633 and IL-6 levels were higher in the children who died in 28 days than the children who were survived, while the PCIS score was lower, and the two groups had significant difference. Spearman correlation analysis showed that the level of circ_0054633 in children with ALI/ARDS was positively correlated with 28-day mortality and IL-6 ( r value was 0.675, 0.763, respectively, all P < 0.001), but negatively correlated with PCIS score ( r = -0.626, P < 0.001), while no significant correlation with LIPS score ( r = 0.389, P = 0.023). Conclusion:The level of serum circ_0054633 has a better value in early diagnosis and prognosis prediction of ALI/ARDS caused in children with severe pneumonia.