OBJECTIVE To analyze the efficacy and safety of luspatercept in the treatment of myelodysplastic syndromes （MDS） anemia， and provide reference for clinical medication. METHODS The literature related to luspatercept for MDS anemia in PubMed， Cochrane Library， Embase and Web of Science were searched by computer， and the search time was from the establishment of the database to January 2024. The quality of literature was evaluated after they were screened according to inclusion and exclusion criteria， the single-group rate meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software， and the subgroup analysis was conducted. RESULTS A total of 756 patients in 9 articles were included in this study. The results of meta-analysis showed that the proportion of MDS patients who reached ≥8 weeks of red blood cell transfusion independence （RBC-TI） was 46% after using luspatercept [95%CI （0.28， 0.64）， P＜0.000 01]. The proportion of MDS patients whose hematological improvement in erythrocyte （HI-E） was 59% [95%CI （0.43， 0.74）， P＜0.000 01]. Among them， 5 articles reported that the proportion of MDS patients with grade 3-4 adverse reactions was 14% [95%CI （0.07， 0.22）， P＝0.000 2]， and the poor general condition， infection， blood and lymphatic system disease were the common adverse reactions. Subgroup analysis showed that the source of heterogeneity was the blood transfusion burden in the proportion of MDS patients with RBC-TI≥8 weeks， and the source of heterogeneity was the 0931-8356251。revised international prognostic scoring system （IPSS-R） risk grade， SF3B1 mutation status and blood transfusion burden in the proportion of MDS patients with HI-E. Sensitivity analysis showed that the results of this study were stable. CONCLUSIONS Luspatercept can significantly improve blood transfusion dependence， reduce blood transfusion burden and promote hematology improvement in MDS patients. But attention should be paid to the occurrence of grade 3-4 adverse events； adverse events such as poor general condition， infection， blood and lymphatic system diseases are more common.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To construct a key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury, and provide a basis for the implementation of such treatment and nursing. Methods The draft of the key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury was determined by literature review, case study, and field investigation. The indicators of the system were determined through two rounds of Delphi consultation and using the precedence chart method. According to the criteria of indicator evaluation, the reliability of expert opinions, and the opinions of the research group, the indicators were refined and evaluated. Results Twenty experts were included for two rounds of consultation via mailed inquiries, with a 100% effective response rate in both rounds. The expert authority coefficients were both 0.945, and the Kendall’s W values were 0.347 and 0.448, respectively (P < 0.05). Following the expert consultations, 1 indicator was deleted, 12 indicators were added, and 6 indicators were modified. The key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury established in this study included 4 first-level indicators, 17 second-level indicators, and 73 third-level indicators. The means of importance assignment for all indicators were > 4.00, and the coefficients of variation were < 0.25. Conclusion The key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury established in this study is scientifically rigorous and practically grounded. The indicators demonstrate strong professional relevance and provide important guidance for in-hospital treatment and nursing of patients with nuclear radiation injury.

OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Objective To investigate the impact of nucleophosmin 1-mutated(NPM1m)subtypes,variant allele frequency(VAF)and co-mutations on the survival outcomes of patients with acute myeloid leukemia(AML).Methods Clinical data,mutation status,and outcomes of 86 NPM1m-AML patients admitted in Department of Hematology,First Hospital of Lanzhou University between June 2017 and September 2024 were collected and retrospectively analyzed.Spearman correlation analysis,Kaplan-Meier curve analysis,Log-rank test,and Cox regression analysis was applied for correlation analysis,survival analysis,and factors affecting survival.Results The overall survival(OS)was significantly shorter in the Rares subtype of NPM1m than the ABD subtype(median OS:164 d vs 416 d,P=0.043).The VAF of NPM1m was positively correlated with the initial peripheral blood white blood cell count and lactate dehydrogenase(LDH)level(P<0.05).OS was reduced when VAF was≥0.37(median OS:164 d vs 730 d,P=0.003).The presence of myelodysplasia-related gene(MR)mutations was associated with a poorer prognosis when compared to the MR wild-type(median OS:45 d vs 395 d,P<0.001).The triple mutation of FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)and DNMT3A also indicated a worse prognosis than the non-triple mutation(median OS:173 d vs 483 d,P=0.007).The presence of PTPN11 mutations was associated with improved OS(median OS:395 d vs 240 d,P=0.027),while the patients with coexistence of N/KRAS mutations trended toward better prognosis than the wild-type patients(median OS:662 d vs 189 d)though no statistical significance(P=0.070).Multivariate analysis revealed that LDH(HR=1.002,95%CI:1.000～1.003,P=0.005),NPM1m VAF(HR=2.415,95%CI:1.208～4.829,P=0.013),Rares subtype(HR=3.037,95%CI:1.134～8.136,P=0.027),and MR mutations(HR=5.283,95%CI:1.991～14.017,P<0.001)were independent risk factors associated with OS in the patients.Conclusion Molecular heterogeneity of NPM1m should be taken into account in prognostic stratification of NPM1m-AML.Factors including the Rares subtype,VAF≥0.37,coexistence of FLT3-ITD and DNMT3A mutations,and MR mutations are associated with poor prognosis of NPM1m-AML.The presence of PTPN11 mutations improves the prognosis,while the presence of N/KRAS mutations shows a trend toward better prognosis.LDH,NPM1m VAF,Rares subtype,and MR mutations are independent risk factors affecting OS of patients with NPM1m-AML.

From the perspective of state differentiation and treatment， it is believed that the pathogenesis of acute respiratory distress syndrome （ARDS） is that evil poisons injured the lungs， and the lung qi suddenly collapsed， then blocked and exhausted， and the qi failure to control blood and liquid， then the fluids overflow outside the vessels， and damp phlegm， stasis， and toxins became knotted up in the body， which ultimately leads to qi dysfunction， and a series of symptom arise， so qi impairment is the principal mechanism of ARDS. A combination of Chinese and Western medicine was proposed to treat ARDS by combining tangible qi and intangible qi， using Chinese herbal medicine to boost qi and relieve collapse， percolate and drain dampness with bland medicinals， resolve toxins and dissolve stasis， and regulate qi， and combining with Western medicine to assist qi circulation to improve qi's consolidation， propulsion， and transformation， so as to make the evil qi go away， the positive qi restored， the viscera qi circulated， qi， blood， yin， and yang connected， and the activities of life maintained， and thus to achieve the goal of treating ARDS by integrated Chinese medicine and Western medicine.

Objective To investigate the role of the TNFRSF12A molecule in the pathogenesis of liver cancer.Methods Through comprehensive analysis of the Cancer Genome Atlas Program(TCGA)database and single-cell sequencing data,we studied the expression of TNFRSF12A in liver cancer and its correlation with prognosis.HPA database was utilized to analyze the subcellular localization of TNFRSF12A,and GO and KEGG analyses were performed by DAVID.TIME 2.0 was employed to analyze the correlation between TNFRSF12A and immune cell infiltration in liver cancer tissues.Results TNFRSF12A was found to be highly expressed in liver cancer tissues,significantly correlating with patient survival prognosis(OS:HR=1.61,P=0.007 0;RFS:HR=1.45,P=0.037 0;PFS:HR=1.30,P=0.099 0;DSS:HR=1.67,P=0.027 0),as well as age(P=0.046 7)and BCLC stage(P=0.045 6).TNFRSF12A co-expressed with tumor stem cell markers(CD24,SOX4,ANPEP),indicating a strong link to malignancy.Furthermore,molecular functional analysis unveiled that IL-2R primarily existed in the cell cytoplasm and played a role in processes such as cell apoptosis,invasion,and protein binding.Moreover,TNFRSF12A was associated with Treg cells and immune cell infiltration,further suggesting its role in tumor immune regulation.Conclusion TNFRSF12A exhibits a significant elevation within liver tumors and shows a notable correlation with patients'prognosis.Tumor cells engage in interactions with cytokines produced by Tregs,thereby reshaping the tumor microenvironment.The potential clinical significance of TNFRSF12A as a prognostic marker for tumors holds promise in offering novel avenues for personalized treatment and prognosis prediction.

UDP glycosyltransferase (UGT) is a terminal modifying enzyme for the formation of flavonoid glycosides. In this study, we obtained two glycosyltransferase genes, CtUGT25 and CtUGT18, which are closely related to the synthesis of safflower flavonoids, through the Pierce correlation analysis of the expression of glycosyltransferase genes in the safflower corolla transcriptome database at different developmental stages with the contents of the major constituents of safflower metabolome database, and bioinformatically analyzed the gene and protein sequences of the two genes. Expression pattern analysis revealed that CtUGT25 was mainly expressed in the corolla, with the highest expression on day 3 of flowering stage; CtUGT18 was mainly expressed in the root, with the highest expression on day 1 of flowering stage. Functional validation was verified in safflower by Agrobacterium-mediated pollen-tube pathway transgenesis method, demonstrating that CtUGT25 promoted the accumulation of kaempferol-3-O-glucoside and hydroxysafflor yellow A (HSYA), and CtUGT18 promoted the accumulation of kaempferol-3-O-glucoside and orientin, both of which may be the glycosyl-modifying enzymes for the synthesis of safflower flavonoids. Meanwhile, in vitro experiments demonstrated the catalytic activity of CtUGT25 protein on naringenin, quercetin, apigenin, kaempferol, luteoin, 2-hydroxynaringenin and galangin. This study serves as reference for future advancements in regulating the quality of safflower using molecular biotechnology, particularly focuses on the industrial production of safflower exclusive component HSYA. Additionally, it offers valuable insights for researching related genes in other plants.