Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

Objective To establish a sensitive,accurate and simple method for the determination of methotrexate and methotrexate polyglutamates(MTXPG2 and MTXPG3)in human erythrocytes.Methods A dual three element gradient liquid chromatograph with a fluorescence detector was used,the C18-WP column(20 mm ×4 mm,5μm)was used as the online SPE column,and the Athena C18-WP column(150 mm x4.6 mm,3 μm)was used as the analytical column.Erythrocyte lysate was precipitated with zinc sulphate-10％formic acid methanol(100:90,v/v),and postcolumn photo-oxidation of MTXPGs to fluorescent analytes using H2O2.The fluorescence excitation wavelength was 274 nm,the emission wavelength was 470 nm,the column temperature was 40 ℃,and the injection volume was 100 μL.The specificity,standard curve,lower limit of quantitation,precision,recovery and stability of the method were investigated.Results MTX,MTXPG2 and MTXPG3 had good linearity in the range of 12.5-400.0 nmol·L-1.The standard curve of MTX was y=763.8x-2 961.1(R2=0.999 5),and the extraction recovery rate was 60.7％-66.1％;the standard curve of MTXPG2 was y=1 017.8x-239.8(R2=0.998 4),and the extraction recovery rate was 67.2％-67.3％;the standard curve of MTXPG3 was y=1 069.1x-819.6(R2=0.999 4),the extraction recovery rate was 62.9％-70.1％.Intra-day precision RSD＜8.8％,inter-day precision RSD＜10.8％.Conclusion This method is accurate and reproducibility,and the online solid-phose extraction enrichment and separation of target compounds simplify the sample pretreatment steps,improve the analysis efficiency,and is suitable for detecting the concentration of MTX,MTXPG2 and MTXPG3 in erythrocytes of patients with rheumatoid arthritis.

Objective To explore the protective mechanism of honey-processed Hedysari Radix in regulating intestinal mucosal injury in rats with spleen qi deficiency.Methods The three-factor composite modeling method of bitter cold diarrhea,overwork and hunger and satiety disorder was used to construct a spleen qi deficiency model rats.After the model was successfully made,they were randomly divided into model group,honey-processed Hedysari Radix group and probiotic group,with 15 animals in each group.Another 15 normal rats were taken as the blank group.The honey-processed Hedysari Radix group was given 12.6 g·kg-1 water decoction of honey-processed Hedysari Radix by gavage,the probiotics group was given Bifidobacterium Lactobacillus triple viable tablets suspension at a dose of 0.625 g·kg-1,and the blank group and the model group were given the same dose of distilled water.The rats in the four groups were administered once a day for 15 days.Enzyme-linked immunosorbent assay was used to detect diamine oxidase(DAO)in serum,D-lactic acid(D-LA),secretory immunoglobulin A factor,and Western blotting was used to detect the expression levels of AMP-activated protein kinase(AMPK),zonula occludens-1(ZO-1)and occludin in colon tissues.Results The serum levels of DAO in the blank group,model group,honey-processed Hedysari Radix group and probiotic group were(138.93±9.78),(187.95±12.90),(147.21±6.92)and(166.47±3.37)pg·mL-1;the contents of D-LA were(892.23±49.17),(1 099.84±137.64),(956.56±86.04)and(989.61±51.75)μg·L-1;the contents of SIgA in colon tissues were(14.04±1.42),(11.47±2.39),(11.84±1.49)and(12.93±1.65)μg·mL-1;the relative expression levels of ZO-1 protein in colon tissues were 1.18±0.11,0.42±0.04,0.77±0.05 and 0.95±0.07;the relative expression levels of occludin protein were 1.35±0.31,0.61±0.17,1.19±0.19 and 0.88±0.13;the relative expression levels of AMPK protein were 0.91±0.02,0.35±0.09,0.74±0.08 and 0.59±0.11.Compared with the model group,there were significant differences in the serum content of DAO and D-LA,SIgA content in colon,and the content of ZO-1,occludin and AMPK protein in the honey-processed Hedysari Radix group(P＜0.01,P＜0.05).Conclusion Honey-processed Hedysari Radix can enhance the protective effect on the intestinal mucosa of rats with spleen qi deficiency by regulating the expression of related inflammatory cytokines,intestinal mucosal upper cell enzymes and tight junction proteins in rats with spleen qi deficiency.

To investigate the role of chamagogic polysaccharides (polysaccharides of Brassica rapa L., BRPs) against doxorubicin (DOX) cardiotoxicity and related mechanisms, H9c2 cells were selected for the study, and the effects of BRPs on DOX induced damage in H9c2 cells were detected by cell counting kit-8 (CCK-8); H9c2 cells were divided into the control group, the model group, and the drug group (0.5-3 mg·mL^-1); the control group was cultured under normal conditions, and the remaining groups were induced for 24 h by 1 μmol·L^-1 DOX after treatment. Apoptosis was detected by flow cytometry; the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in each group; intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected. Western blot was used to detect the expression of proteins related to the apoptosis and transcription factor NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Compared with the control group, DOX-induced H9c2 cell injury was characterized by decreased cell viability, increased apoptosis, elevated LDH and MDA levels, decreased SOD activity, significantly increased ROS levels, and significantly decreased MMP; the level of B cell lymphoma-2 (Bcl-2) protein decreased, and the level of Bcl-2 associated X protein (Bax) increased significantly; In the model group, the expression levels of Nrf-2, HO-1, quinone oxidoreductase 1 (NQO1) were reduced, and the expression levels of Kelch-like ECH-associated protein 1 (Keap1) and phosphorylated p38 mitogen-activated protein kinase were significantly increased, Moreover, BRPs (0.5-3 mg·mL^-1) increased the protein expression levels of Nrf2, HO-1, and NQO1, and decreased the levels of Keap1 and phosphorylated p38 mitogen-activated protein kinase. In summary, the ability of BRPs to protect H9c2 cells and inhibit apoptosis may be related to their regulation of the Nrf2/HO-1 pathway to antagonize oxidative stress.

Objective:To develop and validate a model to predict the risk of malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. Methods:From April 2022 to August 2023, 430 patients with nasopharyngeal carcinoma who were admitted to the department of radiotherapy of the first affiliated hospital of Guangxi medical university in Nanning were conveniently selected as the study subjects, and they were divided into the modelling group (300 cases) and the internal validation group (130 cases) in the internal validation group in the ratio of 7:3, and 61 patients with nasopharyngeal carcinoma admitted to the affiliated cancer hospital of Guangxi medical university in Nanning City were selected as the external validation group. Logistic regression was used to establish the risk prediction model and draw nomograms,Hosmer-Lemeshow, calibration curve and ROC were used to verify the goodness of fit and predictive power of the model, and clinical decision curve was used to assess the clinical utility. Results:Logistic regression analysis showed that skeletal muscle mass index, self-rated anxiety scale score, Pittsburgh sleep quality questionnaire score, Chinese diet pagoda score, regular exercise, and digestive symptom groups were the influencing factors for malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. In the modelling group, the area under the ROC curve was 0.853 (95％CI:0.81 ～ 0.89), the maximum Youden was 0.600, and the corresponding specificity was 0.764 and the sensitivity was 0.836. The Hosmer-Lemeshow test=4.040 and P=0.853 indicated that the model had good predictive ability. Calibration curve of the calibration showed that the predictive effect of the model matched actual probability well, with an average absolute error was 0.024. When the threshold probability of the clinical decision curve is 0.05 ～ 0.85, the clinical response rate is higher. The area under the operating curve of the subjects in the internal validation group was 0.891, the sensitivity was 77.36％, the specificity was 89.61％, and the practical application accuracy was 84.62％. The area under the operating curve of the subjects in the external validation group was 0.886, the sensitivity was 76.00％, the specificity was 83.33％, and the overall accuracy was 80.33％. Conclusion:The risk prediction model constructed in this study has a good effect, which can effectively predict the incidence of malnutrition in patients receiving concurrent radiotherapy and chemotherapy for nasopharyngeal carcinoma, and provide a reference for clinical staff to formulate and implement nutritional interventions.

Objective:To determine the status of nutritional literacy and its influencing factors among the peritoneal dialysis (PD) patients. Methods:The patients who underwent PD and long-term follow-up in the Department of Nephrology,General Hospital of Eastern Theater Command between January and October,2023 were enrolled in this study. The status of nutritional literacy in the patients was assessed through collecting and analyzing the data on the patients' general information,the current nutritional status,and laboratory-and dialysis-related indicators. Results:The average score of nutritional literacy in the enrolled patients were (24.49±3.35). Significant differences in nutritional literacy scoring were observed in the different patient subgroups according to the patients' educational background,dialysis time or times of receiving multidisciplinary diet guidance (all P values<0.05). The nutritional literacy levels of PD patients were negatively correlated to the concentrations of serum calcium and prealbumin,and left ventricular posterior wall thickness,and postively correlated to prealbumin level(P<0.05). Basing on multiple linear regression analysis,the times of receiving multidisciplinary diet guidance,educational background and serum prealbumin level were identified as independent influencing factors for the nutritional literacy levels in PD patients,respectively (all P values<0.05). Conclusions:The present study showed that the nutritional literacy of PD patients was in the middle level. In clinical practice,to enhance multidisciplinary diet guidance and management at the early stage of PD could contribute to improve the nutritional status of PD patients. In addition,to increase the patients' nutritional knowledge and health management ability might be also helpful for the nutritional levels of PD patients.

Objective To investigate the neurodevelopmental characteristics of children with autism spectrum disorder(ASD),analyze the correlation between neurodevelopmental indicators and cerebral blood flow(CBF),and explore the potential mechanisms of neurodevelopment in ASD children.Methods A retrospective study was conducted on 145 children aged 2-6 years with newly-diagnosed ASD.Scores from the Gesell Developmental Diagnosis Scale and the Autism Behavior Checklist(ABC)and CBF results were collected to compare gender differences in the development of children with ASD and analyze the correlation between CBF and neurodevelopmental indicators.Results Fine motor and personal-social development quotient in boys with ASD were lower than those in girls with ASD(P<0.05).Gross motor development quotient in ASD children was negatively correlated with CBF in the left frontal lobe(r=-0.200,P=0.016),right frontal lobe(r=-0.279,P=0.001),left parietal lobe(r=-0.208,P=0.012),and right parietal lobe(r=-0.187,P=0.025).The total ABC score was positively correlated with CBF in the left amygdala(r=0.295,P<0.001).Conclusions Early intervention training should pay attention to gender and developmental structural characteristics for precise intervention in ASD children.CBF has the potential to become a biological marker for assessing the severity of ASD.

Aim To study the effect of salidroside combined with rosavin on ischemic stroke in rats.Methods The model of MCAO was established by u-sing thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside combined with rosavin group,positive control group,and the drug was given continuously for seven days.The infarct volume was measured by MRI and neurological deficit score was evaluated by Zea-Longa.The levels of Ne-uN,BDNF,TGF-β1,p-Smad were observed by West-ern blot and immunofluorescence staining.The expres-sions of IL-1β,TNF-α and IL-6 were performed by RT-qPCR/ELISA.The primary cortical neurons were isolated,OGD/R inducted,divided into the normal group,OGD/R group,salidroside combined with rosa-vin group,and TGF-β1 inhibitor+salidroside com-bined with rosavin group,the drug was given for 24 hours,and the expressions of NeuN,BDNF,IL-1β,TNF-α and IL-6 were measured.Results Salidroside combined with rosavin could decrease the infarct vol-ume,improve the neurological function,promote the levels of Neun,BDNF,TGF-β1,p-Smad,and inhibit the expressions of IL-1β,TNF-α and IL-6.Salidroside combined with rosavin could promote NeuN,BDNF,inhibit IL-1β,TNF-α,IL-6 in primary nerve cells in-duced by OGD/R,and these effects were blocked by TGF-β1 inhibitor.Conclusions Salidroside combined with rosavin has neuroprotective effects on MCAO rats,and primary neurons are induced by OGD/R,and these effects are closely related to the TGF-β pathway.

Objective:To investigate the correlation between serum albumin, urea nitrogen and Fazekas scores and cognitive function scores in patients with mild and medium ischemic stroke.Methods:Clinical data of 160 patients with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS)≤7 scores admitted to the Department of Neurology of the First Affiliated Hospital of Hainan Medical College from June 2021 to April 2023 were selected for a cross-sectional study. According to the Montreal Cognitive Assessment (MoCA) score, they were divided into normal cognitive group (28 cases) (MoCA≥26 scores), mild to moderate cognitive impairment group (74 cases) (MoCA 15-<26 scores), and severe cognitive impairment group (58 cases) (MoCA<15 scores). Demographic characteristics, serological indicators and imaging data of patients were collected, and the correlation between serum albumin, urea nitrogen and Fazekas scores and the total score of MoCA and the scores of each cognitive domain was analyzed. One-way ANOVA was used for comparison between the normal distribution and homogeneous variance data sets, LSD analysis was used for pairwise comparison, Kruskal-Wallis H test was used between the skew distribution or heterogeneous variance data sets. Bonferroni correction analysis was used for pairwise comparison. Chi-square test or Fisher exact probability method was used after the comparison between the count data sets. Spearman Spearman correlation analysis was performed on serum albumin, urea nitrogen and Fazekas scores with MoCA scores and cognitive domain scores. Multivariate ordered Logistic regression was used to analyze the independent risk factors of cognitive function in acute stage of mild and medium ischemic stroke patients. Results:The incidence of cognitive impairment in patients with acute mild and medium ischemic stroke was 82.50% (132/160). Comparison of age ((56.71±7.35), (60.32±10.20), (66.40±11.88) years old), sex (male/female: (23/5, 58/16, 33/25)), the proportion of education level above high school (25.0%(7/28), 16.2%(12/74), 6.9%(4/58)), hemoglobin ((149.26±14.91), (144.85±16.85), (137.63±17.22) g/L), albumin (39.5 (37.0, 41.2), 38.6(35.6, 40.8), 37.4 (34.5, 39.8) g/L), urea nitrogen (5.30 (4.00, 6.60), 4.81 (4.00, 6.32), 5.86 (4.55, 6.97) mmol/L), Hamilton Anxiety Scale (HAMA) score (5.0 (2.0, 10.0), 7.5 (5.0, 11.0), 10.0 (6.0, 14.3) scores),Hamilton Depression Scale (HAMA) score (5.5 (3.0, 12.5), 7.0 (4.0, 11.0), 9.5 (5.0, 14.0) scores), and Fazekas score (2.00 (1.25, 3.00), 2.00 (1.00, 4.00), 3.00 (2.00, 5.00) scores) among cognitive normal group, mild to moderate cognitive impairment group, and severe cognitive impairment group of patients, the difference were statistically significant (the statistical values were F=9.68, χ 2=9.29, χ 2=30.77, F=5.31, H=7.06, H=6.71, H=12.37, H=8.91, and H=10.96, respectively;the P values were <0.001, 0.010, <0.001, 0.006, 0.029, 0.035, 0.002, 0.012, and 0.004, respectively ). The total score of MoCA was negatively correlated with Fazekas score and serum urea nitrogen, but positively correlated with serum albumin ( r s values were -0.250, -0.168, and 0.212, respectively; P values were 0.001, 0.036, and 0.009, respectively). Serum albumin was positively correlated with scores in visual space and execution, naming, attention and orientation, serum urea nitrogen was negatively correlated with scores in language and orientation, and Fazekas score was negatively correlated with scores in visual space and execution, orientation, attention and language ( r s values were 0.291, 0.196, 0.191, 0.209, -0.205, -0.180, -0.248, -0.193, -0.188, and -0.183, respectively; P values were <0.001, 0.017, 0.020, 0.011, 0.012, 0.027, 0.002, 0.016, 0.020, and 0.023, respectively). Multiple Logistic regression analysis showed that low albumin ( OR=0.884, 95% CI: 0.813-0.963, P=0.005) and high urea nitrogen ( OR=1.195, 95% CI: 1.003-1.425, P=0.047) and high Fazekas scores ( OR=1.401, 95% CI: 1.132-1.733, P=0.002) were independent risk factors for cognitive function, while high education level was a protective factor ( OR=0.062, 95% CI: 0.019-0.202, P<0.001). Conclusion:The incidence of acute cognitive impairment is high in patients with mild and medium ischemic stroke. Higher education level is a protective factor for cognitive function. Low albumin, high urea nitrogen and high Fazekas score are independent risk factors for cognitive function.