ObjectiveTo investigate the therapeutic effect of wall-broken ganoderma lucidum spore powder （GLS） on a mouse model of hepatocellular carcinoma and to explore its underlying mechanism. MethodsFifty 2-week-old C57BL/6J mice were divided into a control group， a model group and low， medium and high-dose GLS groups（0.25， 0.5， 1.0 g/kg ）， with 10 mice in each group. A DEN/CCL₄ mouse hepatocellular carcinoma model was established， and GLS was administered by gavage starting from the 8th week， once a day for 14 weeks. At the end of the final administration， the number of liver nodules was observed ， and the serum alpha-fetoprotein （AFP） was detected using enzyme-linked immunosorbent assay. The content of catalase （CAT） in serum and liver tissue was determined by ammonium molybdate method. The content of reduced glutathione （GSH） in serum and liver tissue was measured by microplate assay. The content of glutathione peroxidase （GSH-PX） in serum and liver tissue was detected by colorimetric method. Immunohistochemistry （IHC-P） was employed to detect the protein expression of proliferating cell nuclear antigen （PCNA）. R eal-time fluorescence quantitative polymerase chain reaction was utilized to detect the relative expression of nuclear factor E2-related factor 2 （Nrf2）， Kelch-like epichlorohydrin-associated protein 1 （Keap1）， NAD（P）H quinone oxidoreductase 1 （Nqo1）， heme oxygenase-1 （Ho-1） and glutamate cysteine ligase catalytic subunit （Gclc） mRNA. ResultsCompared with the control group， the content of serum AFP were significantly higher in the model group （P<0.01）， while the contents of CAT， GSH and GSH-PX in liver and serum were significantly lower in the model group （P<0.01）. The relative expression of Keap1 and Nqo1 mRNA was significantly higher （P<0.01）， the relative expression of Nrf2， Ho-1， Gclc mRNA relative expression was significantly lower （P<0.01）， and the positive expression rate of PCNA was significantly higher （P<0.01）. Compared with the model group， the total number of liver nodules and content of serum AFP in the administered group were significantly lower （P<0.01）， and the contents of CAT， GSH， and GSH-PX in the liver and serum of mice significantly increased （P<0.05 or P<0.01）. The expression of Keap1 and Nqo1 mRNA significantly decreased （P<0.05）. The expression of Nrf2， Ho-1 and Gclc mRNA significantly increased （P<0.05）， and positive expression rate of PCNA significantly decreased （P<0.01）. ConclusionGLS has a significant protective effect on DEN/CCL4 -induced mouse hepatocellular carcinoma model， and the mechanism of action is related to the regulation of oxidative stress in mouse liver.

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

AIM:To investigate the effects of ethylisopropylamiloride(EIPA),an inhibitor of Na+/H+ex-changer 1(NHE1),on the proliferation,migration,invasion,cell cycle and apoptosis of hepatocellular carcinoma cells,and to explore its mechanisms.METHODS:The human hepatocellular carcinoma cell line Huh7 was cultured in vitro,and treated with different concentrations of EIPA.The mRNA and protein expression of NHE1 in Huh7 cells was assessed by RT-qPCR and Western blot.The proliferation of Huh7 cells was examined by kFluor488-EdU staining.The migration and invasion of Huh7 cells were assessed by Transwell assays.The cell cycle distribution and apoptosis of these cells were detected by flow cytometry.Moreover,the intracellular pH was measured via the PTI high-speed ion imaging system.RE-SULTS:Treatment with EIPA significantly suppressed the mRNA and protein expression of NHE1(P＜0.01).It signifi-cantly inhibited the proliferation,migration and invasion of Huh7 cells(P＜0.05 or P＜0.01),promoted their apoptosis(P＜0.01),and caused significant S-phase arrest(P＜0.01).It also significantly reduced the intracellular pH of Huh7 cells.CONCLUSION:The NHE1 inhibitor EIPA regulates the intracellular pH by inhibiting the expression and function of NHE1,which consequently affects the proliferation,migration,invasion,cell cycle,and apoptosis of Huh7 cells.There-fore,NHE1 may be a potential target for the treatment of hepatocellular carcinoma.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

In analytical techniques such as ion mobility spectrometry(IMS)and mass spectrometry(MS),the ionization efficiency of target analytes is primarily constrained by the type of ionization source and factors such as the species and number density of the reactant ions.Systematic investigation into the reactivity differences of various reactant ions under varying conditions can not only significantly enhance the detection sensitivity of target compound product ions but also provide a theoretical foundation for establishing efficient detection methods based on ion-molecule reaction mechanisms.In this study,the pressure of a pressure-tunable photoionization tandem ion mobility spectrometry(PI-tandem-IMS)was reduced from ambient pressure(100 kPa)to low pressure(20 kPa)to systematically examine the reactivity differences between two negative reactant ions,CO3-and CO4-,and methyl salicylate(MeSA)under varying pressures.When the pressure decreased,the increased relative signal intensity of CO4-significantly influenced the detection sensitivity of the characteristic product ion[MeSA·O2]-.Based on differences in ion mobility(k0),the delay time for the opening of TPG2 was adjusted to selectively inject CO-3 and CO-4 in the drift region 2.Independent characterization of the reactivity of these reactant ions with MeSA in the reaction region confirmed that CO4-exhibited superior reactivity toward MeSA.The theoretical model revealed an Arrhenius plot for the ion-molecule reaction between CO4-and MeSA,showing a positive correlation between the reaction rate coefficient(k)and temperature,the activation energy Ea was 62.45 kJ/mol.Furthermore,controlling parameters such as pressure or temperature significantly influenced the progression of this ion-molecule reaction,demonstrating the technical advantages of PI-tandem-IMS in mechanistic studies and regulation of ion-molecule reactions.

The resolving power and sensitivity are critical for on-site detection of hazardous chemicals using stand-alone ion mobility spectrometry(IMS).However,improving the sensitivity and resolving power of IMS has long been a prominent research hot spot.In the commonly used IMS based on the Bradbury-Nielsen gate(BNG),the gating voltage difference(GVD)applied between the two sets of grid wires affects the electric field distribution in the ionization region and the drift region.This,in turn,influences the spatial distribution and temporal width of the injected ion swarm,and has an impact on the ion mobility discrimination,sensitivity,and resolving power of the instrument.This study showed that increasing the GVD could induce an ion converging effect,boosting the ion number density in front of the BNG by nearly 300％.To simultaneously utilize temporal compression and ion converging effects,a novel BNG controlling mode was proposed by adding a chopping state to the conventional controlling mode.This chopping state reduced the mobility discrimination effects between ions with mobility differences up to about 0.90 cm2/(V·s)to 1/22 of their original value.When analyzing hazardous chemical mixtures using the novel BNG controlling mode,compared with conventional mode,the signal intensity of low-mobility methyl salicylate ions(MS·O2)-increased by 18-fold while the resolving power maintained around 100,and the detection limit for MS was improved from 3.75 μg/L to 97 ng/L.This novel BNG controlling mode only added a potential wave to the low voltage wires,with no requirement of changing the structure of the drift tube,and was easy to apply to existing commercial instruments.

Objective:To investigate the relationship between alterations in dynamic functional connectivity (dFC) and spatial navigation abilities in individuals with subjective cognitive decline (SCD) across different Traditional Chinese Medicine (TCM) constitutions.Methods:Seventy-five participants with SCD, comprising 34 individuals with balanced constitutions and 41 individuals with biased constitutions, were recruited from the Affiliated Drum Tower Hospital of Nanjing University Medical School between August 2022 and January 2025. The participants underwent TCM constitution assessment, spatial navigation ability testing, and neuropsychological scale evaluation. Additionally, each participant was assessed using 3.0 T resting-state functional magnetic resonance imaging (rs-fMRI) and high-resolution T1-weighted imaging scans. Based on prior research, 20 spatial navigation-related regions of interest (ROIs) were defined. Afterwards, rs-fMRI time series were segmented using a sliding time window approach before calculating the dFC within the spatial navigation brain network.Results:Compared to the balanced constitution group, the biased constitution SCD group showed significantly lower scores on the Mini-Mental State Examination (MMSE) ( z=-3.05, P=0.002) and the Auditory Verbal Learning Test (AVLT) measures: immediate recall ( z=-2.12, P=0.035), short-delay recall ( z=-2.22, P=0.026), long-delay recall ( z=-2.88, P=0.004), cued recall ( z=-2.91, P=0.004), and recognition ( z=-2.20, P=0.028). They also exhibited significantly higher average error distances in ego-allocentric navigation ( z=-2.28, P=0.023), egocentric navigation ( z=-2.31, P=0.021), and delayed navigation ( z=-2.02, P=0.043). Participants with SCD who had a biased constitution also demonstrated significantly reduced dFC between the left parahippocampal gyrus (PHG) and left prefrontal cortex (PFC) ( t=2.43), right precuneus and right retrosplenial cortex (RSC) ( t=2.96), and left inferior parietal lobule (IPL) and left hippocampus ( t=2.42) (all P<0.05, Bonferroni-corrected). Conversely, the dFC was significantly increased between the right PHG and left PFC ( t=-2.29, P<0.05, Bonferroni-corrected). Significant correlations were also found in participants with SCD who had biased constitutions: the dFC between the left PHG and left PFC positively correlated with the egocentric navigation average total error ( r=0.34, P=0.030) and negatively correlated with the visuospatial memory cognitive domain ( r=-0.35, P=0.026); the dFC between the left IPL and left hippocampus negatively correlated with the egocentric navigation average total error ( r=-0.32, P=0.043); and the dFC between the right PHG and left PFC positively correlated with the delayed navigation average total error ( r=0.33, P=0.037). The area under the ROC curve for the combined differences in cognitive assessments, spatial navigation behavior, and navigation-related brain network dFC was 0.966 in predicting biased constitution versus balanced constitution in participants with SCD. Conclusions:Individuals with SCD and biased constitutions demonstrated poorer spatial navigation ability, possibly due to altered dFC within the spatial navigation brain network. Furthermore, the integrated model based on spatial navigation behaviors and dFC exhibited a high predictive value in distinguishing between individuals with SCD who had balanced and biased constitutions.

Objective:To explore the research hotspots and emerging trends in the field of breast cancer-associated lymphedema, as reflected in the domestic and international literatures.Methods:The bibliometric method was used to retrieve literatures related to breast cancer-associated lymphedema from the Wanfang Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and the core collection of Web of Science, covering the time range from January 1, 2014, to December 31, 2023. CiteSpace 6.3.R3 software was employed for analysis, which involved statistical assessment of the publication volume, authors, countries, and institutions, as well as the identification of highly cited papers. A co-occurrence analysis of keywords was performed, followed by burst analysis and cluster analysis based on the results.Results:A total of 4 419 Chinese-language articles were retrieved from the three Chinese databases, of which 2 888 were included after duplicate removal. The Web of Science Core Collection yielded 2 142 English-language articles. Among the domestic authors, the top three with the highest publication counts were Zhang Lijuan (25 papers), Jia Jie (22 papers), and Zhong Qiaoling (21 papers). In the English-language literatures, the top three authors with the highest number of publications were Singhal D (32 papers), Devoogdt N (27 papers), and Boyages J (27 papers). A total of 76 countries worldwide had conducted research on breast cancer-associated lymphedema, with the United States contributing the most publications (748 papers), followed by China (227 papers). In total, 642 institutions worldwide had publications on this topic, with 385 domestic institutions. The leading domestic institution was Jiangxi Provincial Cancer Hospital (31 papers), while the top foreign institution was Harvard University (118 papers). The Top 10 most cited papers focused on key research areas in breast cancer-associated lymphedema. A total of 359 Chinese keywords and 513 English keywords were included for co-occurrence analysis. The five most frequent Chinese keywords were quality of life, nursing, complications, upper limb function, and risk factors. In the English literatures, the top five most frequent keywords were quality of life, women, survivors, risk factors, and surgery. Cluster analysis of the keywords revealed 16 clusters in the Chinese literatures, with the largest cluster "functional exercise", while 17 clusters were identified in the English literatures, with the largest cluster "lymph node transfer". The five most consistent clusters in Chinese literatures were lymphatic drainage, rehabilitation, functional impairment, evidence-based nursing, and circumferential lymphatics. In recent years, emerging topics in Chinese literatures included lymphatic drainage, breast reconstruction, and pathophysiology. In English literatures, the consistent top clusters were transplantation, node biopsy, morbidity, identification, and randomized trials, with recent emerging topics including obesity, adipose tissue, healing approaches, lymphatic microsurgical preventive healing approach, and anastomosis.Conclusion:The research on breast cancer-related lymphedema both domestically and internationally shows similarities and differences in direction and focus. Common research hotspots across both domestic and international studies include lymphatic drainage, functional exercise, health behaviors, and lymph node transfer. Recent emerging topics in Chinese literatures include lymphatic drainage, breast reconstruction, and pathophysiology. In contrast, English literatures focus more on the areas such as obesity, adipose tissue, healing methods, and lymphatic anastomosis.

Objective:To explore the therapeutic effect of Bupiqiangli compound on experimental myasthenia gravis with sub-clinical hypothyroidism in rats and the influence of hypothalamus-pituitary-thyroid-thymus(HPTT)axis.Methods:SPF Lewis rats were randomly divided into normal group,model group,Bupiqiangli compound low-dose,medium-dose and high-dose groups.Model rats were immunized with AchR-α subunit 97-116 peptide sequence to construct an experimental myasthenia gravis model,and then methimazole was used to prepare an experimental myasthenia gravis with subclinical hypothyroidism model.Bupiqiangli compound low-dose,medium-dose and high-dose groups were given 4.57 g/kg,7.12 g/kg and 9.49 g/kg of Bupiqiangli compound by gavage,nor-mal group and model group were given an equal volume of normal saline by gavage,once a day,for 4 weeks.After the last gavage,Lennon scores of rats in each group were recorded;HE staining was used to detect pathological changes of thymus and thyroid;ELISA was used to detect expression levels of acetylcholine receptor antibody(AchRab),thyroid stimulating hormone(TSH),thyrotropin releasing hormone(TRH),free thyroxine(FT4)and thyroxine(T4)in serum;mRNA level of TRH in hypothalamus and TSH in pituitary tissue were detected by qPCR;Western blot detected changes of protein expressions of Cleaved Caspase3,Bcl2 associated X protein(Bax)and B-cell lymphoma-2(Bcl2)in thymus.Results:Compared with normal group,model group showed obvious symp-toms of muscle weakness,Lennon score increased significantly(P<0.05),obvious pathological changes in thymus and thyroid tissues,while no significant changes in expressions of FT4 and T4 in serum(P>0.05),expressions of AchRab,TSH and TRH in serum were significantly increased(P<0.05),expressions of TRH in hypothalamus and TSH in pituitary were significantly increased(P<0.05),protein expressions of Cleaved Caspase3 and Bax in thymus were significantly decreased(P<0.05),while expression of Bcl2 protein in thymus increased significantly(P<0.05).Compared with model group,myasthenia symptoms of compound high-dose group were im-proved,Lennon score was significantly decreased(P<0.05),pathological changes of thymus and thyroid tissues were improved,ex-pressions of FT4 and T4 in serum had no significant changes(P>0.05),expressions of AchRab,TSH and TRH in serum were signifi-cantly decreased(P<0.05),expressions of TRH in hypothalamus and TSH in pituitary were significantly decreased(P<0.05),expres-sions of Cleaved Caspase3 and Bax in thymus were significantly increased(P<0.05),while expression of Bcl2 in thymus was signifi-cantly decreased(P<0.05).Conclusion:Bupiqiang compound can improve clinical symptoms of experimental myasthenia gravis with subclinical hypothyroidism in rats,and its mechanism may be related to the regulation of HPTT axis.