Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Flowering and bolting are important agronomic traits in cruciferous crops such as Brassica juncea. Timely flowering can ensure the crop organ yield and quality, as well as seed propagation. The WRKY family plays an important role in regulating plant bolting and flowering, while the function and mechanism of WRKY12 in B. juncea remain unknown. To explore its function and mechanism in bolting and flowering of B. juncea, we cloned and characterized the BjuWRKY12 gene in B. juncea and found that its expression levels were significantly higher in flowers and inflorescences than in leaves. BjuWRKY12 belonged to the Ⅱc subfamily of the WRKY family, and subcellular localization indicated that the protein was located in the nucleus. Ectopic overexpression of BjuWRKY12 in transgenic lines promoted bolting and flowering, leading to significant increases in the expression levels of flowering integrators SOC1 and FUL. Furthermore, yeast one-hybrid and dual luciferase reporter system assays confirmed that BjuWRKY12 directly bound to the promoters of BjuSOC1 and BjuFUL, undergoing protein-DNA interactions. This discovery gives new insights into the regulation network and molecular mechanisms of BjuWRKY12, laying a theoretical foundation for the breeding of high-yield and high-quality varieties of B. juncea.
Mustard Plant/metabolism* ; Flowers/growth & development* ; Plant Proteins/physiology* ; Promoter Regions, Genetic/genetics* ; Gene Expression Regulation, Plant ; Plants, Genetically Modified/genetics* ; Transcription Factors/metabolism* ; MADS Domain Proteins/metabolism*

Macrophages are closely related to tumor progression,and can promote tumor growth and pro-liferation by promoting inflammation,angiogenesis and immunosuppression and so on,as well as killing tumors by directly killing tumor cells and triggering specific immune responses.Iron death,as an iron-depend-ent cell death caused by lipid peroxidation,can effectively kill tumor cells when regulated from the perspective of iron homeostasis,and can also release pro-inflammatory factors,trigger inflammatory reactions,change the survival environment of tumors as well as reduce the immune susceptibility of tumor cells.In recent years,more and more studies have shown that macrophages and iron death are closely related.In this paper,the rela-tionship between macrophages and iron death in terms of their functional properties and targeting of tumors are mainly introduced,and an overview of the functional properties of the two differentiated phenotypes of macrophages for the treatment of iron death in tumors is provided.

Objective To explore the application effect of blood pressure management based on the health belief model in patients with moyamoya disease after cerebral vascular reconstruction sur-gery.Methods From February to July 2024,210 patients with moyamoya disease who underwent cerebral vascular reconstruction surgery in our hospital were selected as study subjects.They were randomly divided into control group and intervention group,with 105 cases in each group.The control group received routine nursing care,while the intervention group applied blood pressure management based on the health belief model on the basis of routine nursing care.The postoperative cerebral hy-perperfusion syndrome and blood pressure control status of the two groups were compared,and the Health Belief Scale and the Mishel Uncertainty in Illness Scale were used to evaluate the effects before and after intervention.Results A total of 203 patients completed the study,including 100 cases in the control group and 103 cases in the intervention group.There were statistically significant differ-ences in the incidence of cerebral hyperperfusion syndrome and the proportion of patients with blood pressure higher than baseline data between the two groups(P＜0.05).After the intervention,there were statistically significant differences in the postoperative cerebral hyperperfusion syndrome status and blood pressure control status between the two groups(P＜0.05).After intervention,there were statistically significant differences in the scores of susceptibility and health motivation dimensions as well as the total score in the Health Belief Scale between the intervention group and the control group(P＜0.05).After the intervention,there were statistically significant differences in the scores of ambiguity and unpredictability dimensions as well as the total score in the Mishel Uncertainty in Ill-ness Scale between the intervention group and the control group(P＜0.05).Conclusion Blood pressure management based on the health belief model can effectively control blood pressure,reduce the incidence of cerebral hyperperfusion,improve health beliefs,and reduce the sense of uncertainty about the disease.

Objective To investigate the effects of ATP-binding cassette subfamily B transporter 6 subfamily B(ABCB6)on cognitive dysfunction in Alzheimer's disease(AD)rats and its possible potential regulatory molecular mechanisms.Methods Amyloid β-protein(Aβ)was injected to construct the AD mouse model in vivo.Water maze test and Y maze test were used to evaluate the learning and memory ability and space exploration ability of rats.An in vitro AD cell model was constructed by HT22 cells and Aβ.The binding relationship between YTH domain containing 1(YTHDC1)and ABCB6 was analyzed by RNA immuniprecipitation(RIP).Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect overexpression and knockdown transfection efficiency.Western blot analysis was performed to detect the expression levels of YTHDC1 and ABCB6 proteins,as well as ferroptosis related proteins[Solute Carrier Family 7 Member 11(SLC7A11),Glutathione peroxidase 4(GPX4)].Cell viability was detected with CCK-8.Malondialdehyde(MDA),Glutathione(GSH),Reactive oxygen species(ROS)levels and Fe2+content were analyzed by the assay kit.Results The ABCB6 mRNA(3.51±0.17 vs 1.02±0.01,3.45±0.21 vs 1.02±0.01)and protein(3.25±0.14 vs 1.01±0.01,3.14±0.16 vs 1.01±0.01)levels in the hippocampus of AD mice and Aβ-induced HT22 cells were up-regulated,and the differences were statistically significant(t=-46.238,-20.349;-50.468,-23.013,all P<0.001).Knocking down ABCB6 decreased the time and distance of AD mice reaching the platform,and increased the ratio of spontaneous exchange rate to the number of times of entered the new arm(t=27.007,11.264,24.414,19.901,all P<0.001).Knockdown ABCB6 promoted HT22 cell proliferation,decreased levels of MDA and Fe2+,increased GSH levels,reduced ROS generation,and promoted expression of SLC7A11 and GPX4 proteins(t=2.883～26.122,all P<0.05).YTHDC1 protein promoted its stability by binding to ABCB6 mRNA and up-regulated the expression of ABCB6 protein.Knockdown of YTHDC1 decreased ABCB6 protein level(t=18.504,P<0.001),promoted the proliferation of HT22 cells,increased GSH content,SLC7A11 and GPX4 protein levels,decreased MDA and Fe2+content,and inhibited ROS production(t=4.404～14.486,all P<0.05).Knocking down YTHDC1 could improve the learning and memory ability and spatial exploration ability of AD mice.Over-expression of ABCB6 reversed the effects of YTHDC1 knockdown on ferroptosis in HT22 cells and cognitive dysfunction in AD mice.Conclusion YTHDC1 may induce ferroptosis of neuronal cells by mediating the up-regulation of ABCB6,thus promoting cognitive dysfunction in AD mice.

Objective To explore the clinical value of models based on clinical features and enhanced MRI radiomics for predicting the occurrence of post-acute pancreatitis diabetes mellitus(PPDM-A).Methods A retrospective selection of 161 acute pancreatitis(AP)patients was conducted,comprising 99 in the non-PPDM-A group and 62 in the PPDM-A group.They were randomly divided into training set and test set in a ratio of 7∶3.Region of interest(ROI)were delineated and radiomics features were extracted on the late arterial phase MRI images.Optimal radiomics features were selected by maximum relevance and minimum redundancy(mRMR)and least absolute shrinkage and selection operator(LASSO).Support vector machine(SVM)was used to develop three predictive models.The efficacy of the models in predicting PPDM-A was evaluated,the receiver operating characteristic(ROC)curve was drawn,and the DeLong test was employed to assess the difference in predictive capability among the models.Results In the training set,the area under the curve(AUC)of the clinical model,radiomics model,and combined model were 0.702,0.810 and 0.901,respectively,and in the test set were 0.678,0.797 and 0.830,respectively.The DeLong test revealed a statistically significant difference in the predictive capability of the combined model compared to the clinical model both in the training and test sets(training set:P＜0.001;test set:P=0.019).Conclusion The combined model based on clinical features and enhanced MRI radiomics features demonstrates good predictive effi-cacy and can provide valuable insights for clinical interventions aimed at preventing PPDM-A.

Objective To investigate the risk factors of hip instability in elderly patients with femoral neck fracture after hemiarthroplasty(HA).Methods The medical records of 133 patients with femoral neck fracture who received HA treatment in the Department of Orthopedics of our hospital from January 2015 to October 2022 were retrospectively collected.According to whether the patients suffered hip dislocation after surgery,the patients were divided into dislocation group(n=35)and non-dislocation group(n=98).Demographic variables such as age,sex and body mass index(BMI)were recorded in the two groups.Complications such as diabetes,hypertension,heart disease and chronic obstructive pulmonary disease(COPD)were recorded.Prosthetic type,surgical approach,soft tissue repair type,blood loss and other surgical phase variables were recorded.Central marginal Angle(CEA),extraneous Angle(ABA),eccentricity,lower limb length difference(LLD),acetabular width,acetabular depth,and femoral head coverage(FCR)were measured on radiographs.Wald method was used to establish Logistic regression model to elucidate the risk factors of dislocation after HA.Results The proportion of COPD in the dislocation group was significantly higher than that in the control group(P＜0.05),and there was no significant difference in baseline characteristics between the two groups(P＞0.05).There was no significant difference between the two groups(P＞0.05).There were no significant differences in CEA,ABA,LLD,acetabular width,eccentricity and FCR between 2 groups(P＞0.05),but the acetabular depth and depto-width ratio in luxation group were significantly lower than those in control group(P＜0.05).Gender,COPD,CEA,acetabular width-to-depth ratio and LLD were independent risk factors for hip instability after HA(P＜0.05).Conclusion In this study,COPD,male,LLD,and small CEA and acetabular broad-to-depth ratio are independent risk factors for hip instability after HA,and therefore HA is not recommended for the treatment of femoral neck fractures in elderly patients with these conditions.

Objective:To investigate the clinical features of patients with chronic obstructive pulmonary disease (COPD) and serum-positive specific IgE (SIgE).Methods:This study was a retrospective cohort study. A total of 105 stable COPD patients with allergic features and completed serum SIgE testing were included, and all of them were from Capital Medical University, Beijing Tong Ren Hospital from September 2022 to October 2023. Those with at least one positive result of SIgE testing were classified as positive SIgE COPD group, and those with negative SIgE were classified as negative SIgE COPD group. There were 32 cases (30.5%) in the positive SIgE COPD group and 73 cases (69.5%) in the negative SIgE COPD group. Differences in laboratory tests, pulmonary function, chronic obstructive pulmonary symptom scores, incidence of severe acute exacerbation events in the past year, and drug therapy were compared between the two groups. The risk factors for positive SIgE COPD were analyzed, and the best predictive value for the diagnosis of positive SIgE COPD was analyzed using the area under the curve (AUC) of receiver operating characteristic (ROC).Results:Compared with the negative SIgE COPD group, the percentage of positive SIgE COPD group with rhinitis, sinusitis, sinusitis with nasal polyps, eczema, and a history of drug or food allergy were higher (all P<0.05) and the percentage of those who had quit smoking were higher ( P<0.05); the percentage of IgE above normal thresholds, the level of IgE, the percentage of peripheral blood eosinophil (EOS%), the count of EOS, and fractional exhaled nitric oxide (FeNO) were higher (all P<0.05), and the percentage of those who had severe and above severe Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) pulmonary function classification were higher, while the percentage of forced expiratory volume in one second (FEV 1% predicted), 25% maximal expiratory flow (MEF 25%) and MEF 75/25% were lower, and FEV 1/FVC was higher (all P<0.05). The positive SIgE COPD group had higher modified British medical research council (mMRC) scores and COPD assessment test (CAT) scores, and a higher incidence of severe acute exacerbation events over the past year (all P<0.05), and the use of short-acting β 2 receptor agonists (SABA) or short-acting muscarinic antagonist (SAMA), inhaled corticosteroid (ICS), theophylline and oral hormone therapy were more frequent (all P<0.05). EOS% ( OR=1.252, 95% CI: 1.039-1.508) was a risk factor for SIgE positivity in COPD ( P<0.05), and having quit smoking ( OR=0.385, 95% CI: 0.197-0.751) was a protective factor ( P<0.05). The AUC value of the ROC curve of EOS%>2.5% for the diagnosis of SIgE positivity was 0.647 (95% CI: 0.543-0.752), with a sensitivity and specificity of 52.8% and 73.1%, respectively. Conclusions:Positive SIgE COPD has sever clinical symptoms, high risk of acute exacerbation and deficiencies in treatment. The elevate of EOS% is a risk factor for the development of positive SIgE in COPD patients; positive SIgE COPD meets the diagnostic criteria for allergic COPD phenotype, and EOS% over 2.5% is suggestive of the clinical detection of allergic COPD phenotype.

AIM: By analyzing the effect of gambogenic acid (GNA) on the mRNA expression profile of melanoma xenograft model mice, the possible mechanism of GNA in the treatment of melanoma was explored. METHODS: The inhibitory effect of GNA on melanoma cells was studied by measuring the cell survival rate by MTT method in vitro and observing the cell morphology under an inverted microscope. In the in vivo experiment, the effect of GNA on the growth of xenografted tumors in melanoma mice was observed by comparing the results of HE (hematoxylin-eosin) staining and immunohistochemistry (Ki-67), and the tumor weight and tumor weight ratio were recorded. RNA-seq sequencing technology was used to sequence the GNA medium-dose group and the model group, and the screened mRNAs were analyzed by GO and KEGG, and finally the screening results of differentially expressed genes were verified by real-time quantitative fluorescent PCR. RESULTS: After different doses of GNA acted on the melanoma mouse model, a large area of necrosis occurred in the tumor tissue of the model mouse, and the tumor growth was significantly inhibited. A total of 36 differentially expressed mRNAs were identified by mRNA sequencing, of which 30 were up-regulated and 6 were down-regulated. The possible functions of the mRNAs were predicted according to the genomic adjacency analyzed by GO and KEGG. The expression of the selected differential mRNAs was further verified by real-time quantitative PCR technology. The results showed that the mRNA expressions of Cidec, Ces1d, Mylk4, and Igkv9-123 were up-regulated, and the mRNA expressions of Ryr3 and Hapln1 were down-regulated. CONCLUSION: GNA can inhibit the proliferation of melanoma cells in vitro and in vivo, and its mechanism is related to the regulation of cytokine-cytokine receptor interaction, NF-κB, MAPK, and other pathways of mRNA expression.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.