ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription （JPXA） in ameliorating the 5-fluorouracil （5-FU） resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations （10%， 15%， 20%） of JPXA-containing serum and drug-free serum were used for intervention， and 10% fetal bovine serum （10% FBS）， fibroblast growth factor receptor （FGFR） inhibitor （AZD4547）， and recombinant fibroblast growth factor 2 （FGF2） were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group， while HCT116/5-FU cells were used in other groups. Drug resistance， the level of FGF2 in the cell culture medium， the mRNA level of FGF2 in cells， and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model， JPXA （15 g·kg^-1）， 5-FU （0.02 g·kg^-1）， JPXA+5-FU （15 g·kg^-1+0.02 g·kg^-1）， AZD4547 （0.012 5 g·kg^-1）， and AZD4547+5-FU （0.012 5 g·kg^-1+0.02 g·kg^-1） groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased， and the decrease was the most significant in the 20% group （P<0.01）. HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 （p-FGFR1）， but down-regulated protein level of FGFR1 （P<0.01）. JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 （P<0.05）. In addition， JPXA down-regulated the expression levels of phosphorylated protein kinase B （p-Akt） and phosphorylated mammalian target of rapamycin （p-mTOR）， while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter （Bad） （P<0.05）. Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors， reduced the protein levels of FGF2， p-FGFR1， phosphorylated phosphatidylinositol-3-kinase （p-PI3K）， p-Akt， and p-mTOR， and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

Objective:Elderly patients with sarcopenia and cognitive impairment are prone to experiencing more severe adverse events.This study aimed to analyze body composition and gait characteristics in this population, as well as to identify sensitive gait indicators of sarcopenia in individuals with cognitive impairment.Methods:A total of 200 elderly individuals from 3 different nursing homes in Suzhou were recruited for this study.The participants' overall cognitive function was assessed using the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ), body composition was evaluated through bioelectrical impedance analysis, and gait was assessed using a wearable gait analysis system.Gait predictors of sarcopenia with cognitive impairment were then identified and used to construct predictive models.Results:The study encompassed 83 participants, divided into three groups: 35 in the control group(cognitively normal, without sarcopenia), 24 in the sarcopenia with mild cognitive impairment(MCI)group, and 24 in the sarcopenia with dementia group.When compared to the control group, individuals in the sarcopenia with MCI group exhibited lower Skeletal Muscle Mass Index[(5.6±0.8)kg/m 2vs.(7.4±0.8)kg/m 2], Total Protein[(6.7±1.1)kg vs.(8.9±1.5)kg], and Arm Muscle Circumference[(21.4±1.7)cm vs.(24.1±2.3)cm](all P<0.05).Similarly, in comparison to the control group, those in the sarcopenia with dementia group displayed a shorter stride length[(0.45±0.17)m vs.(0.65±0.22)m], slower gait speed[(0.38±0.13)m/s vs.(0.55±0.18)m/s], smaller turn velocity[(89.8±23.4)degrees/s vs.(116.8±26.3)degrees/s], and longer turn duration[(3.2±0.5)s vs.(2.8±0.3)s](all P<0.05).Notably, turn duration was identified as having predictive value for sarcopenia with MCI[Area under the curve(AUC)=0.673, sensitivity 70.8%, specificity 68.6%], while a model incorporating age and turn velocity demonstrated strong predictive power for sarcopenia with dementia(AUC=0.87, sensitivity 83.3%, specificity 85.7%). Conclusions:Compared to the control group, the group with both sarcopenia and cognitive impairment exhibited lower levels of muscle strength, nutritional status, and gait performance.This study also introduced the concept that gait indicators associated with turns could be a significant predictor of sarcopenia in individuals with cognitive impairment.Furthermore, the use of wearable devices for gait assessment may offer a novel approach to identifying these at-risk individuals.

Objective:To explore the health behavior of middle-aged and young stroke patients and analyze its influencing factors.Methods:From April to July 2023, convenience sampling was used to select 172 middle-aged and young stroke patients admitted to the First Affiliated Hospital of Naval Medical University as the research subject. A survey was conducted using the General Information Questionnaire, Health Behavior Scale for Stroke Patients, Health Belief Scale, and Multidimensional Scale of Perceived Social Support. Spearman correlation was used to analyze the correlation between health behavior, social support, and health beliefs among middle-aged and young stroke patients. Multiple linear regression was used to analysis the influencing factors of health behavior among middle-aged and young stroke patients. A total of 172 questionnaires were distributed, and 8 questionnaires with missing items and short response times were excluded, and 164 valid questionnaires were collected, with a valid response rate of 95.34%.Results:Among 164 middle-aged and young stroke patients, the total score of the Health Behavior Scale for Stroke Patients was 64.50 (57.00, 80.75), and the average score of the items was 2.58 (2.28, 3.23). Multiple linear regression analysis showed that factors affecting the health behavior of middle-aged and young stroke patients were whether it was the first onset, the time required to reach nearby medical institution, health belief, and social support ( P<0.05) . Conclusions:The health behavior of middle-aged and young stroke patients is above the medium level. In the process of intervening in the health behavior of middle-aged and young stroke patients, medical and nursing staff should pay attention to patients with recurrent stroke and poor access to medical services, while also improving patients' health belief and social support to promote patients' health behavior and reduce stroke recurrence.

Objective:To explore the mediating effect of coping style on disease perception and pre-hospital delayed behavioral intention in patients with acute ischemic stroke.Methods:This study was a cross-sectional study. From February to July 2023, convenience sampling was used to select 205 patients with acute ischemic stroke admitted to the First Affiliated Hospital of Naval Medical University as the study subject. The survey was conducted using the General Information Questionnaire, Stroke Pre-Hospital Delay Behavior Intention, Brief Illness Perception Questionnaire, and Simplified Coping Style Questionnaire.Results:205 questionnaires were filled out, 195 valid questionnaires, and the validity rate of the questionnaire was 95.1%. The Stroke Pre-Hospital Delay Behavior Intention score of patients with acute ischemic stroke was (63.61±16.12). Pre-hospital delayed behavioral intention in patients with acute ischemic stroke was positively correlated with disease perception and negative coping ( r=0.360, 0.266; P<0.01), and negatively correlated with positive coping ( r=-0.279, P<0.01). The mediating effects of positive and negative coping on disease perception and pre-hospital delayed behavioral intention in ischemic stroke patients were 0.111 and 0.097, respectively, accounting for 26.89% and 23.49% of the total effect. Conclusions:There is a partial mediating effect of coping strategies between disease perception and pre-hospital delayed behavioral intention in ischemic stroke patients. In the process of stroke management, medical and nursing staff can reduce pre-hospital delayed behavioral intentions by improving disease cognition and coping style.

By referring to the relevant literature on the application of positive psychology in patients with cognitive impairment at home and abroad, this paper reviews the measurement tools, interrelationships and intervention status of positive psychology in patients with cognitive impairment, and explores the prospects of its application in this population. The aim is to provide a basis for nursing decision-making in patients with cognitive impairments.

Objective To select a safe,low-cost basal medium in combination with platelet lysate(PL),suitable for the growth of human umbilical cord mesenchymal stem cells(hUC-MSCs)with no influence on the functions of cells during the cultivation process,and to use it for the culture of a large number of high-generation hUC-MSCs.Methods Three different basal media,MSCBM,α-MEM and IMDM,were mixed with PL UltraGROG Advanced respectively to culture hUC-MSCs from P0 to P8. The cell morphology,cell expansion quantity,proliferation function,differentiation function and cell surface markers of different generations were compared to determine the optimal basal medium suitable for hUC-MSCs cultivation.Results The morphology of P1-P5 cells cultured in the three media was uniform and radial,with no significant difference between them and the standard cells(t_(IMDM VS α-MEM)= 0. 159,t_(MSCBM VS α-MEM)= 0. 147,t_(IMDM VS MSCBM)= 0. 161;each P > 0. 05). The morphology of P6-P8 cells cultured in MSCBM and α-MEM showed no significant difference compared with that of P0-P5cells(t_(IMDM VS MSCBM)= 0. 132,t_(IMDM VS α-MEM)= 0. 128;each P > 0. 05). The positive expression rate of CD73,CD90 and CD105all reached about 99% in P1-P8 cells cultured in MSCBM,α-MEM and IMDM,while the expression of CD34 and CD45 was negative with the expression rate of lower than 2%,and there was no significant difference among different media(t_(IMDM VS α-MEM)= 0. 102,t_(MSCBM VS α-MEM)= 0. 106,t_(IMDM VS MSCBM)= 0. 113;each P > 0. 05). The clonal formation of P8 cells cultured in the three media was different,the numbers of single clonal cluster and MSCBM cells in clonal cluster were higher than those of the same generation cells cultured in α-MEM and IMDM(t = 0. 023 and 0. 049,respectively,each P < 0. 05). The proliferative function of cells cultured in the three media from high to low was MSCBM,α-MEM and IMDM,among which,the proliferation function of cells cultured in MSCBM was significantly higher than that in IMDM(t = 0. 041,P < 0. 05),while there was no significant difference between MSCBM and α-MEM(t = 0. 211,P > 0. 05). The result of doubling time(DT)was consistent with the proliferation function. The cells of the same generation cultured in the three media all had strong differentiation function,and there was no significant difference in the number of osteoblasts and chondroblasts differentiated from P8 cells(t_(IMDM VS α-MEM)= 0. 119,t_(MSCBM VS α-MEM)= 0. 112,t_(IMDM VS MSCBM)= 0. 111,each P > 0. 05). The number of adipoblasts differentiated from P8 cells cultured in MSCBM was higher than that from P8 cells cultured in α-MEM(t =0. 036,P < 0. 05),and the number of adipoblasts differentiated from P8 cells cultured in α-MEM was higher than that in IMDM(t = 0. 031,P < 0. 05).Conclusion In this study,the optimal culture system of hUC-MSCs was MSMBM with 5%UltraGROG Advanced,followed by α-MEM with 5% UltraGROG Advanced,and these two serum-free culture systems were suggested to be selected for large-scale culture of MSCs.