It has been popular and challenging to undertake researches on the delay of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). As key cells for tumor initiation, cancer stem cells (CSC) play an important role in the process of resistance to EGFR-TKI. Although preliminary studies found that traditional Chinese medicine (TCM) could inhibit CSC properties and delay EGFR-TKI resistance, the specific molecular mechanism remains unclear. By summarizing the empirical syndrome treatment of EGFR-TKI resistance via TCM and combining recent researches on TCM intervention in CSC to delay EGFR-TKI resistance, this review discussed the potential molecular pathways and mechanisms of deceleration in resistance to EGFR-TKI by TCM via inhibiting CSC characteristics, in order to expand the research ideas of TCM in combination with targeted therapy.
Humans ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Medicine, Chinese Traditional ; Neoplasms/drug therapy* ; Animals ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVES: To propose a single repetition time (TR) quantitative magnetic susceptibility imaging method for the lumbar spine using bipolar readout gradient, and compare the quantitative magnetic susceptibility measurement using single TR and dual TR methods for the lumbar spine with different bone densities. METHODS: A translation correction method was proposed to correct spatial misalignment along the frequency encoding direction between positive and negative gradient readout images, and the phase difference between the images was eliminated using a phase correction method. The data of lumbar vertebrae L1-L5 were collected using single TR and dual TR methods from 6 normal individuals, 2 patients with osteopenia, and 2 patients with osteoporosis. The magnetic susceptibility map was reconstructed, the quantitative results of single TR before and after correction were compared with those of the dual TR method. RESULTS: The linear regression result of the lumbar spine magnetic susceptibility values obtained by the single TR method before calibration and the dual TR method is Y=0.64*X-11.61. The linear regression result of the lumbar spine magnetic susceptibility values corrected by the single TR method and the dual TR method is Y=1.03*X+0.25. The results of the corrected single TR method were highly consistent with those of the dual TR method, and the calibrated single TR method could effectively distinguish osteopenia and osteoporosis patients from normal individuals. CONCLUSIONS The calibrated single TR bipolar readout gradient method can generate artifact-free lumbar spine quantitative magnetic susceptibility distribution maps and reduce data acquisition time by 50%.
Humans ; Lumbar Vertebrae/pathology* ; Magnetic Resonance Imaging/methods* ; Female ; Middle Aged ; Male ; Osteoporosis/diagnosis* ; Adult ; Bone Density ; Aged ; Bone Diseases, Metabolic/diagnosis*

Objective To explore the causal association between gut microbes and non-alcoholic fatty liver disease(NAFLD)by Mendelian randomisation analysis.Methods Genetic instrumental variables for gut microbiota were identified from a gene-wide association study of 18 340 participants,and summary statistics for NAFLD were ob-tained from the FinnGen database,which provided data on 894 NAFLD cases and 217 898 controls using the IVW method as the primary analysis.In order to test the robustness of the results,MR-Egger method,WM method,Simple Mode method,Weighted Mode method were used for Mendelian randomisation analysis,and heterogeneity test,sensitivity analysis,and multiplicity analysis were performed.Results class Gammaproteobacteria IVW re-sults showed(OR=0.621,95％CI=0.412～0.934,P=0.022);family Enterobacteriaceae IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018);genus Lachnospiraceae IVW results showed(OR=1.405,95％CI=1.036～1.904,P=0.029);genus Prevotella7 IVW results showed(OR=0.834,95％CI=0.714～0.974,P=0.021);genus Prevotella9 IVW results showed(OR=1.251,95％CI=1.025～1.527,P=0.027);order Desulfovibrionales IVW results showed(OR=0.714,95％CI=0.519～0.982,P=0.038);or-der Enterobacteriales IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018).And there was no heterogeneity in the heterogeneity test,and the sensitivity analyses all showed robustness and no pleiotropy was found.Conclusion This study implicates class Gammaproteobacteria,family Enterobacteriaceae,genus Lachno-spiraceae,genus Prevotella7,genus Prevotella9,order Desulfovibrionales,order Enterobacteriales seven species of gut microorganisms have a causal relationship with NAFLD.

OBJECTIVE To investigate the improvement effects of glycyrrhizin （GL） on Helicobacter pylori （HP）-associated gastritis in rats and its mechanism. METHODS HP-associated gastritis rat model was induced by inoculating with 1×109 cfu/mL HP. The model rats were randomly divided into model group， positive control group （HP standard quadruple group）， GL low-dose， medium-dose and high-dose groups （5， 20， 50 mg/kg）， with 12 rats in each group. Another 12 healthy rats were selected as normal control group. Except the normal control group and model group were given constant volume of normal saline intragastrically， the other groups were given corresponding drugs intragastrically， once a day， for 30 consecutive days. After administration， rats received 13C urea breath test， and delta-over-baseline （DOB） was recorded； the pathological and cellular morphological changes of gastric mucosa in rats were observed， and pathological scoring was performed； the levels of interleukin-8 （IL-8）， IL-1β， tumor necrosis factor-α （TNF-α）， reactive oxygen species （ROS） and malondialdehyde （MDA） were detected in gastric mucosa of rats； mRNA expressions of high mobility group box-1 protein （HMGB1） and nuclear factor-κ-B （NF-κB）， relative expressions of nitric oxide synthases （iNOS） and HMGB1， the phosphorylation level of NF- κBp65 were also detected in rats. RESULTS Compared with normal control group， the DOB value， histopathological score of gastric mucosa， the levels of IL-8， IL-1β， TNF-α， ROS and MDA， relative expressions of HMGB1 and NF- κB mRNA， relative expressions of iNOS and HMGB1 protein and the phosphorylation level of NF-κB p65 were all increased significantly in model group （P＜0.05）； the epithelial cells of gastric mucosa in rats were incomplete in structure and decreased in the number， with an increase in cell fragments and vacuoles， and significant cell pyknosis. Compared with model group， the changes of the above indexes in GL groups and positive control group were significantly reversed （P＜0.05）； the changes in the above indicators in the GL high-dose group were more significant than GL low-dose and medium-dose groups （P＜0.05）； the pathological changes of gastric mucosal cells in rats had all improved. CONCLUSIONS GL may inhibit inflammation and oxidative stress by inhibiting the activation of HMGB1/NF-κB pathway， thus relieving HP-induced gastric mucosal injury.

OBJECTIVE To study the inhibitory effect and mechanism of total flavonoids from Melicope pteleifolia （TF-MPL） on transplanted tumor of colorectal cancer in nude mice. METHODS The transplanted tumor model of colorectal cancer was induced by injecting 0.2 mL colorectal cancer cell LoVo subcutaneously via the right armpit of nude mice. After successful modeling， nude mice were randomly divided into model group， 5-fluorouracil group （positive control， 10 mg/kg）， TF-MPL high- dose and low-dose groups （25， 12.5 mg/kg）； a normal group （normal saline containing 0.3% carboxymethyl cellulose sodium） without modeling was additionally set up， with 6 mice in each group. Each group was intraperitoneally injected with the corresponding drug solution/solvent for 21 consecutive days. The inhibitory rate of the transplanted tumor， liver and spleen index， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected after the last medication； the morphological changes of tumor tissue were observed； immunohistochemical staining was used to detect protein expressions of Toll- like receptor 4 （TLR4） and nuclear factor-κB subunit p65 （NF-κB p65） in tumor tissue of nude mice. Western blot assay was used to detect protein expressions of TLR4， myeloid differentiation factor 88 （MyD88）， TNF receptor-associated factor 6 （TRAF6）， interleukin-1 receptor-associated kinase 1 （IRAK-1）， NF-κB p65 and caspase-3 in tumor tissue of nude mice. RESULTS Compared with the model group， TF-MPL high-dose group showed a significant decrease in tumor weight （inhibitory rate of 36.91%）， liver and spleen index， serum levels of TNF-α and IL-6 and protein expressions of TLR4， MyD88， TRAF6，IRAK-1 and NF- κB p65 （P＜0.05 or P＜0.01）； the expression of caspase-3 protein was increased significantly （P＜0.05）， and more tumor cell shrinkage and deformation， nuclear pyknosis and fragmentation were observed. CONCLUSIONS TF-MPL can significantly inhibit the growth of transplanted tumor of colorectal cancer in nude mice， the mechanism of which may be associated with reducing inflammatory response， inhibiting TLR4/MyD88/NF-κB signaling pathway， and promoting apoptosis in colorectal cancer cells.

Objective:To build a systematic and standardized nutrition management plan for patients with chronic kidney disease.Methods:Based on the nutrition care procedure and model, a preliminary draft of a nutrition management plan for chronic kidney disease patients was developed through a literature search, quality evaluation, and group discussions. After two rounds of expert consultation and revision of the preliminary draft of the nutrition management plan, the final plan was formed.Results:A total of 32 experts were invited to complete two rounds of consultation. In two rounds of expert consultation, 32 questionnaires were distributed, and 32 and 31 valid questionnaires were collected, with valid response rates of 100.0% and 96.9%, respectively. The expert authority coefficients were 0.853 and 0.871, respectively. The final nutrition management plan for chronic kidney disease patients included six first-level items of nutrition management personnel: nutrition risk screening, nutrition assessment, nutrition treatment, nutrition monitoring, and nutrition health education, with 23 second-level and 52 third-level items.Conclusions:The constructed nutrition management plan for chronic kidney disease patients is scientific and can provide a reference for nutrition guidance.

Objective To investigate the level of benefit finding and positive psychological capital of stroke patients and their spouses,and to analyse the dyadic interaction between benefit finding and positive psychological capital of patients and their spouses.Methods From March to August 2023,235 stroke patients and their spouses were conveniently selected from the neurology wards of 3 tertiary hospitals in Henan Province,and were surveyed using a general information questionnaire,the positive psychological capital questionnaire,revised version of benefit finding scale,and caregiver benefit finding scale.Results The positive psychological capital scores of stroke patients and their spouses were(4.29±0.75)and(4.56±0.71);benefit finding scores of the dyads were(2.85±0.69)and(3.64±0.68).The results of actor-partner interdependence model showed that positive psychological capital of stroke patients and their spouses positively predicted their benefit finding;positive psychological capital of patients positively predicted benefit finding of spouses,and positive psychological capital of spouses positively predicted benefit finding of patients(all P＜0.05).In particular,spousal self-efficacy and resilience positively predicted their benefit finding;their optimism positively predicted the patient's benefit finding;their hopefulness negatively predicted the patient's benefit finding(all P＜0.05).Conclusion There was a dyadic interaction between benefit finding and positive psychological capital for stroke patients and their spouses.The role of spouses on patients'positive psychological capital should not be overlooked,and nurses should develop positive psychological capital intervention strategies centered on couples of stroke patients to enhance positive couple experiences.

Objective To investigate the current status of health behavioral decision-making in ischemic stroke patients and analyze its influencing factors.Methods Totally 250 ischemic stroke patients were selected from 2 hospitals in Zhengzhou and Anyang from February to May 2023.A general information questionnaire,Behavioral Decision-Making Scale for Stroke Patients,Recurrence Risk Perception Scale for Patients with Stroke,and Stroke Self-Efficacy Questionnaire were used to conduct the questionnaire survey.Results The Behavioral Decision-Making Scale for Stroke Patients score of 229 ischemic stroke patients was(117.83±7.15)scores.The results of multiple linear regression analysis showed that occupational status,glycemic compliance,primary caregiver,current symptoms,stroke self-efficacy,and recurrence risk perception were the influencing factors of health behavioral decision making in ischemic stroke patients(P＜0.05).Conclusion The health behavioral decision making of ischemic stroke patients is at an upper-middle level.Individualized interventions can be carried out for patients with different characteristics to promote the patients'ability to behavior decision making and the formation of preventive behaviors.

Objective To explore the categories of dyadic mental health literacy among stroke patients and their caregivers,and to analyze the differences in the characteristics of different classes of stroke patients and their caregivers.Methods A convenient sampling method was used to select 287 dyads of stroke patients and their caregivers who were treated at a tertiary general hospital in Henan province from July to October 2020.The general information questionnaire,Multicomponent Mental Health Literacy and Social Support Rating Scale were used for investigation.Latent profile analysis was adopted to explore the categories of dyadic mental health literacy,and multiple logistic regression was used to analyze the influencing factors of each category.Results Stroke patients and their caregivers were divided into 4 categories based on scores of mental health literacy:dyadic low resource group(19.86％),dyadic low literacy group(54.36％),dyadic low belief group(11.15％),dyadic high literacy group(14.63％).The patient's age,average monthly household income,the caregiver's age,the caregiver's Social Support Rating Scale score,the caregiver's educational level,daily care time and total time length of care were the factors influencing the categories of dyadic mental health literacy among stroke patients and their caregivers(P＜0.05).Conclusion Stroke patients and their caregivers were divided into 4 categories based on scores of mental health literacy.Medical staff should carry out comprehensive psychological interventions for stroke patients and their caregivers with different dyadic mental health literacy characteristics,so as to improve dyadic mental health literacy.

OBJECTIVE To investigate the effect and mechanism of anwulignan on improving hepatic fibrosis in rats. METHODS Fifty SD rats were randomly divided into the normal group， model group， colchicine tablet group （0.1 mg/kg）， and anwulignan high-dose and low-dose groups （2.8 and 0.7 mg/kg）， with 10 rats in each group. Except for the normal group， all groups of rats were intraperitoneally injected with 50% CCl4 olive oil mixed solution to replicate the rat model of liver fibrosis. At the end of the modeling， rats in each group were given the corresponding drugs or distilled water intragastrically from the 9th week， once a day， for 4 weeks consecutively. During the experimental period， the general condition of the rats was observed； the liver index was calculated； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by colorimetric assay； the pathomorphology of the liver tissues and liver fibrosis were observed by HE staining and Masson staining； Western blot was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway and apoptosis-related proteins in liver tissues. RESULTS Compared with the normal group， the dietary amount of rats in the model group decreased， with sparse and disheveled fur， slow response， and a slower rate of weight growth or weight loss； the liver index was significantly increased （P＜0.01）； the serum levels of ALT， AST and MDA were significantly increased， and the SOD level was significantly decreased （P＜0.01）； HE and Masson staining showed that a large amount of fibrous proliferation was present in the liver tissues of the rats， and the collagen volume fraction was significantly increased （P＜0.01）； the protein expressions of PI3K， Akt， phosphorylated Akt and B-cell lymphoma （Bcl-2） were down-regulated significantly， while the protein expression of Bcl-2-associated X protein was increased significantly （P＜0.01）. Compared with the model group， the above indexes of the anwulignan high-dose and low-dose groups and the colchicine tablets group were all reversed significantly. CONCLUSIONS Anwulignan may reduce oxidative stress and inhibit hepatocyte apoptosis by activating the PI3K/Akt signaling pathway， and play the role of anti-hepatic fibrosis.