ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

ObjectiveMolecular docking plays a critical role in predicting binding modes and affinity between molecules, serving as a pivotal method in structural biology and computer-aided drug design research. Our research team has recently developed a novel template-based docking method called FitDock, which outperforms commonly used molecular docking methods in terms of accuracy and speed, particularly when approximate protein-ligand templates are available. To enhance the accessibility of the FitDock method and promote its broader application in the field of molecular simulation, the development of a graphical software tool is imperative. MethodsUtilizing Python-based graphical programming, we have created FitDockApp, a plugin software for the molecular visualization software PyMOL. ResultsFitDockApp enables template-based molecular docking and ligand structure alignment through an interactive graphical interface, providing real-time visualization of predicted three-dimensional structures. It also offers the convenience of uploading docking files to a laboratory server to obtain the optimal template. Additionally, FitDockApp includes batch docking functionality. ConclusionFitDockApp simplifies the docking process through its user-friendly interface and provides robust functionality to assist researchers in obtaining precise docking results. FitDockApp is a free software compatible with both Windows and Linux systems and can be downloaded from http://cao.labshare.cn/fitdock/.

Objective To investigate the effects of exercise and complex environment on lipopolysaccharide(LPS)-induced dopaminergic neuron death in the substantia nigra of midbrain.Methods C57BL/6 mice were divided into control group,LPS group,LPS+swimming group and LPS+complex environment group,with 7 mice in each group.The mice in the LPS group were injected with LPS into the brain to establish an inflammatory model of Parkinson's disease and lived in cages for 2 weeks.Mice in LPS+swimming group were forced to swim for 15 minutes every day for 2 weeks after modeling.The mice in the LPS+complex environment group were placed in a complex environment for 2 weeks after modeling.The control group mice were not treated.After 14 days of modeling,behavioral experiments such as footprint,open field and rotating rod were performed on each group of mice to detect the autonomous exercise ability,exercise balance ability and depression level of mice.The expressions of tyrosine hydroxylase(TH)in substantia nigra was detected by immunohistochemical staining and Western blotting.The expressions of brain-derived neurotrophic factor(BDNF),Caspase-3,interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the substantia nigra of the midbrain were detected by Western blotting.The transcription levels of IL-1β,IL-6 and TNF-α in substantia nigra were detected by RT-PCR.Results Compared with the control group,the exercise ability and balance ability of mice in LPS group,LPS+swimming group and LPS+complex environment group decreased,the depression level increased(P＜0.001),the number of TH positive neurons and BDNF protein decreased significantly(P＜0.001),and the contents of Caspase-3,IL-1β,IL-6 and TNF-α increased significantly(P＜0.001).Compared with the LPS group,the exercise ability and balance ability of the mice in the LPS+swimming group and the LPS+complex environment group were restored,the depression level decreased significantly(P＜0.01),the survival number of TH positive neurons and the content of BDNF increased significantly(P＜0.01),Caspase-3,IL-1β,IL-6 and TNF-α reduced significantly(P＜0.01),and the phenomenon in the LPS+complex environment group was more significant.Conclusion Exercise and complex environment can inhibit LPS-induced central nervous system inflammation in mice,thereby reducing damage to midbrain substantia nigra neurons,and the inhibitory effect of LPS+complex environment group is more significant.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

To elucidate the mechanism of Euodiae Fructus stir-fried with water decoction of Coptidis Rhizoma in the treatment of chronic colitis, this study employed ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, and experimental verification to predict the involved targets and signaling pathways. The chronic colitis mouse model was constructed to verify the core targets. A total of 48 compounds in the herbal medicine were identified by UPLC-Q-TOF-MS. SwissTargetPrediction was used to screen the potential active components and drug targets. GeneCards, OMIM, PharmGKB, and TDD were used to search for the disease targets. A total of 31 active ingredients, 453 targets of the herbal medicine, and 3 960 targets of chronic colitis were obtained. The common targets shared by the herbal medicine and chronic colitis were introduced into STRING to construct the protein-protein interaction(PPI) network, and CytoNCA plug-in was used to screen the key targets. A total of 90 key targets were obtained, and the key active components included isorhamnetin, quercetin, limonin, and oxyberberine. GO annotation and KEGG pathway enrichment for the key targets were carried out via DAVID. The targets were mainly involved in the positive regulation of protein phosphorylation, positive regulation of nitric oxide biosynthetic process, and negative regulation of apoptotic process. The medicine may treat chronic colitis through PI3 K-Akt, VEGF, HIF-1, and TNF signaling pathways. A mouse model of chronic colitis was established and then treated with Euodiae Fructus stir-fried with the water decoction of Coptidis Rhizoma. The experimental results demonstrated that the medicine can alleviate the pathological damage of colon, significantly reduce the levels of IL-1β, IL-6, and TNF-α, inhibit the activation of PI3 K/Akt pathway, and down-regulate the expression of VEGFA in the treatment of chronic colitis.
Animals ; Mice ; Water ; Drugs, Chinese Herbal/pharmacology* ; Network Pharmacology ; Proto-Oncogene Proteins c-akt ; Colitis/drug therapy* ; Chronic Disease ; Molecular Docking Simulation

Charcot-Marie-Tooth Disease/genetics* ; DNA-Binding Proteins/genetics* ; Humans ; Mutation ; Transcription Factors/genetics*

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Neuroblastoma/drug therapy* ; Positron-Emission Tomography ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome

Gallic Acid/pharmacology* ; Humans ; Senotherapeutics ; Stem Cells

ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution （A）-acetonitrile （B）as mobile phase for gradient elution （0-0.01 min， 20%B； 0.01-5 min， 20%-40%B； 5-40 min， 40%-95%B； 40-42 min， 95%B； 42-42.1 min， 95%-20%B； 42.1-45 min， 20%B）， electrospray ionization （ESI） was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3， the components were identified according to the primary and secondary MS data， and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1， the MS data were analyzed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode， including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water， and 10 differential components （alisol B 23-acetate， alisol I， alismol， 11-deoxy-alisol B 23-acetate， alisol B， alisol C， 11-deoxy-alisol B， alisol G， 11-deoxy-alisol C and alisol A） were screened， and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing， and the difference of substituents is the main reason for this differences， which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.