Objective:To investigate the expression of protein kinase D2(PRKD2)in bladder cancer(BLCA)tissue using bioinformatics analysis method and its effect on the prognosis of BLCA patients,and to clarify the role of PRKD2 in the occurrence and development of BLCA.Methods:The data from 9 normal bladder samples,19 BLCA paracancerous samples,and 407 BLCA tumor samples were downloaded from the UCSC Cancer Genome Database.The Mann-Whitney U test was applied to analyze the difference in expression of PRKD2 mRNA in BLCA tumor and normal bladder tissues,and the Human Protein Atlas(HPA)database was used for proteomic validation.DESeq2 package in R software was applied to screen the differentially expressed genes(DEGs)in BLCA tissue in PRKD2 low-and high-expression groups.The co-expression heatmaps of PRKD2 were plotted using the ggplot2 package,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation analysis and pathway enrichment analysis of DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the gene sets that were significantly enriched for DEGs.The BLCA samples were divided into low-and high-expression groups according to the expression level of PRKD2,and the correlations between PRKD2 expression and immune cell infiltration in the BLCA patients were analyzed with GSVA package.The relationship between PRKD2 and prognosis of BLCA patients was further analyzed using the survival package and the survminer package.The PRKD2 gene mutations in BLCA tissue were analyzed using the cBioPortal database.The cystitis,bladder polyp and BLCA tissues were collected,and the expression levels of interleukin-17F(IL-17F)protein in BLCA and control tissues were detected using immunohistochemical staining technique.Results:PRKD2 was highly expressed in a variety of malignant tumors,and the expression levels of PRKD2 mRNA and protein in BLCA tissue were significantly increased compared with those in normal bladder tissue(P＜0.05).Single gene differential analysis of PRKD2 yielded a total of 1 058 DEGs,of which a total of 29 genes were up-regulated and 1 029 were down-regulated.The results of GO functional enrichment analysis showed that DEGs were mainly enriched in the biological process(BP),such as chemical stimuli involved in sensory perception,Cajal body,and endopeptidase inhibitor activity.The results of KEGG pathway analysis showed that DEGs were mainly enriched in the pathway of Staphylococcus aureus infection and the pathway of maturity onset diabetes of the young.GSEA analysis showed that DEGs were mainly enriched in the Notch signaling pathway,the retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ)-like receptor signaling pathway,the cytoplasmic DNA screening pathway,the base excision repair signaling pathway,natural killer(NK)cell-mediated cytotoxicity signaling pathway and T cell receptor signaling pathway.The results of immune infiltration analysis indicated that the expression of PRKD2 was positively correlated with five types of cells,such as activated dendritic cells(aDC),NK CD56dim cells and central memory T cells(Tcm)(P＜0.05),and negatively correlated with three types of immune cells,including macrophages,effector memory T cells(Tem)and plasmacytoid dendritic cells(pDC)(P＜0.05).The clinical characteristic subgroup analysis results showed that the expression levels of PRKD2 mRNA in BLCA patients who were over 70 years old and developed lymphovascular invasion were decreased(P＜0.05);the overall survival(OS),disease-specific survival(DSS)and progression-free interval(PFI)in the BLCA patients with PRKD2 high expression were significantly longer than those with PRKD2 low expression(P＜0.05).The univariate and multivariate Cox analyses indicated that distant metastasis,primary therapy outcome and clinicopathologic stage were the important factors affecting BLCA prognosis.About 9％patients had PRKD2 gene mutations,including missense mutation,gene amplification,mRNA low or high expression,and multi-motif mutation.The immunohistochemistry results showed that the expression level of IL-17F protein in BLCA tissue was significantly higher than that in cystitis tissue(P＜0.05).Conclusion:The expression level of PRKD2 in BLCA tissue is obviously increased,which could up-regulate the expression of IL-17F protein,and the decrease of PRKD2 protein expression may be a potential factor for the poor prognosis of BLCA patients.

Objective To compare the hemodynamic effects of anesthesia induction with remimazolam tosylate and etomidate in elderly frail patients.Methods This study was a single-center,prospective,randomized,single-blind trial.From January to April 2024,96 elderly frail patients undergoing elective surgery in Fuyang People's Hospital were recruited.After excluding 6 cases(3 refused to participate,1 had tracheal intubation time＞30 s,and 2 had missing data),90 patients were finally included.They were randomly divided into remimazolam tosylate group(intravenous injection of 0.2 mg/kg remimazolam tosylate for anesthesia induction,n=45)and etomidate group(intravenous injection of 0.3 mg/kg etomidate for anesthesia induction,n=45)by the random number table method.The area under the curve for mean arterial pressure(MAP)below or above baseline values(AUCMAP-and AUCMAP+),the heart rate(HR)below or above baseline values by 10％(AUCHR-and AUCHR+)within 10 minutes of anesthesia induction,the time to loss of consciousness,the time from the start of anesthesia induction to a bispectral index(BIS)＜60,the incidence of drug-related adverse reactions,the incidence of cardiovascular adverse events,and the usage of vasoactive drug administrations were compared between the two groups.Results Compared with the etomidate group,the AUCMAP-(145.10±35.75 vs.178.52±39.78)and AUCHR-[43.20(26.58,56.35)vs.54.99(43.01,65.85)]in remimazolam tosylate group were significantly reduced(P＜0.001,P=0.001).The time to loss of consciousness and the time from the start of anesthesia induction to BIS＜60 were prolonged(P＜0.001).The incidence of drug-related adverse reactions was significantly decreased(P＜0.05),and the number of norepinephrine administrations was significantly reduced(P＜0.05)in remimazolam tosylate group.However,there were no statistically significant differences in AUCMAP+,AUCHR+,the incidence of cardiovascular adverse events,and the usages of atropine,urapidil,and esmolol between the two groups(P＞0.05).Conclusion The use of remimazolam tosylate during anesthesia induction in elderly frail patients can provide more stable hemodynamic parameters and results in fewer adverse reactions than etomidate.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To analyze the B_el subtype gene mutation and its genetic mechanism in a family line. METHODS: ABO blood groups were identified by serologic tests. ABO genotyping was performed by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sanger sequencing was performed on exons 1-7 of the ABO gene, the flanking intronic region, and exon 7 of the single strand of the gene confirmed the mutation site location. Missense3D software was used to predict the protein structure alteration caused by this mutation. RESULTS: Conventional serologic tests failed to detect erythrocyte B antigen in the proband and her three family members, and only trace amounts of B antigen expression could be detected by the absorption-dispersal test. DNA analysis showed that, on the basis of the normal ABO gene, there was a G>T substitution in the position of exon 7, position 803, which resulted in the change of amino acid 268 from Gly to Val. Further single-stranded sequencing analysis showed that the mutation site was located in the B gene. CONCLUSION In this family line, the proband, her father, her son, and her daughter all have reduced B type glycosyltransferase activity due to the new point mutation (c.803G>T) in exon 7 of the B gene, and the B antigen can only be detected by the absorption-dispersal method, and the point mutation can be stably inherited by offspring.
Point Mutation ; Alleles ; ABO Blood-Group System/genetics* ; Exons ; Introns ; Genotype ; Humans ; Male ; Female ; Glycosyltransferases/genetics*

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Purpose/Significance To explore the training mode of medical engineering integration composite technical talents in the major of medical information engineering,in order to cope with the transformation of medical and health models and contribute to the Healthy China 2030 strategy.Method/Process It explores the innovative training mode for the major of medical information engineering from 3 aspects of curriculum system,faculty team,and quality assurance,emphasizes cross-disciplinary integration,builds interdisci-plinary teams,and improves the monitoring system.Result/Conclusion The mode contributes to more versatile technical talents who can adapt to the needs of intelligent medicine,provides strong support for the transformation of medical and health models,and provides refer-ence for other medical engineering integration majors.

This study was aimed at examining the influence of meteorological factors on scrub typhus in Xiamen.Scrub ty-phus monitoring data and meteorological factors were collected in Xiamen from 2005 to 2023.Spearman correlation analysis and nonlinear regression were used to analyze the correlation between scrub typhus incidence and meteorological factors.The inci-dence of scrub typhus first increased and subsequently decreased in Xiamen from 2005 to 2023.The highest incidence was be-tween 2014 and 2016,and the peak incidence was from June to October.The monthly incidence of scrub typhus positively cor-related with daily minimum temperature(r=0.637,P＜0.001,daily average temperature(r=0.627,P＜0.001),daily maxi-mum temperature(r=0.612,P＜0.001),sunshine duration(r=0.405,P＜0.001),average relative humidity(r=0.346,P＜0.001),and daily rainfall(r=0.207,P=0.002),and negatively correlated with average atmospheric pressure(r=-0.549,P＜0.001),whereas no correlation was observed with the average wind speed in Xiamen.The regression equation of scrub ty-phus monthly incidence and meteorological parameters was y=-433.869-11.503x1+0.381x1 2+9.150x2-0.197x2 2+3.936 x3-0.132x3 2+0.881x4+0.035x4 2-1.048x5+0.009x5 2+0.186x6-0.023x6 2+0.421x7+6.210×10-5x8-1.051 × 10-10x8 2 in Xiamen,and the R2 was 0.473,thus indicating good model fit.Scrub typhus incidence correlated with the daily minimum av-erage temperature,average temperature,daily maximum tem-perature,sunshine duration,daily rainfall,relative humidity,and average atmospheric pressure in Xiamen.Various meteoro-logical factors had differing effects on scrub typhus.

Objective:To explore the effect of UV radiation resistance-associated gene(UVRAG)on ferroptosis induced by sorafenib in leukemia K562 cells.Methods:K562 cells were treated with 0,0.625,1.25,2.5,5,10,and 20μmol/L sorafenib for 24 or 48 hours,and the cell viability was detected by CCK-8 assay.Flow cytometry technology was used to detect the changes of reactive oxygen species(ROS)in K562 cells treated with 0,5,and 10 μmol/L sorafenib for 24 hours.Western blot was used to detect the protein expression of GPX4 in K562 cells treated with 0,5,and 10μmol/L sorafenib and pretreatment with ferroptosis inhibitor.A recombinant lentiviral vector was used to construct UVRAG overexpression cell line in K562 cells.qPCR and Western blot were used to verify UVRAG gene overexpression,and Western blot detected the effect of UVRAG on the protein expression of GPX4 and HMGB1 after treatment with sorafenib.Results:Different concentrations of sorafenib could significantly inhibit the proliferation of K562 cells,and the cell viability gradually decreased with the increase of concentration(r24h=-0.9841,r48 h=-0.9970).The level of ROS was increased(When the concentration was 10 μmol/L,P＜0.00 1),while the expression of GPX4 protein was decreased in the process of 0,5,10 μmol/L sorafenib-induced K562 cell death(P＜0.05),and the decrease in GPX4 protein could be partially reversed by pretreatment with ferroptosis inhibitor(P＜0.05).Compared with NC group and NC-Sorafenib group,the expression of GPX4 protein was significantly decreased(both P＜0.05),while HMGB1 protein was significantly increased(both P＜0.05).Conclusion:Sorafenib can induce ferroptosis in K562 cells,and this process can be promoted by UVRAG.

Aim To study the regulatory effect of poly-datin on D-galactose-induced aging model mice.Methods Fifty-six ICR mice(half male and half fe-male)were divided into normal group,model group,positive group,low,medium and high polydatin treat-ment groups.Aging model was established by subcuta-neous injection of D-galactose(500 mg·kg-1)into the back of neck every day.During the modeling peri-od,the positive group was given donepezil hydrochlo-ride tablets(0.75 mg·kg-1)by gavage,the treat-ment group was given polydatin(40,70,100 mg·kg1)by gavage,and the normal group was given the same amount of normal saline.The learning and cogni-tive ability of mice was evaluated by nesting experi-ment,new object recognition experiment and Morris water maze experiment.The heart,liver,spleen,kid-ney and thymus of mice were taken to calculate the or-gan index.The pathological changes of whole brain tis-sue in mice were observed by hematoxylin-eosin(HE)staining.The levels of T-SOD,MDA,GSH-Px and AchE in serum and whole brain tissue of mice were de-tected by ELISA.The protein expression levels of Keap1,Nrf2 and HO-1 in hippocampus of mice were detected by Western blot.Results Compared with the model group,the nesting ability,the ability to recog-nize new objects and the ability to find platforms under-water of the mice in the positive group and the low,medium and high dose groups of polydatin were im-proved.The organ index increased.The neuronal dam-age in the cerebral cortex and hippocampus was signifi-cantly ameliorated.The activities of T-SOD and GSH-Px in serum and brain tissue increased and the activi-ties of MDA and AchE decreased.The expression lev-els of Nrf2 and HO-1 protein in hippocampus in-creased,and the expression level of Keap1 protein de-creased.Conclusions Polydatin can ameliorate the learning and cognitive impairment in D-galactose-in-duced aging model mice,and its mechanism may be related to the Keap1/Nrf2/HO-1 pathway.

Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is a recognition protein for N⁶-methyladenosine (m⁶A), mediating the stability of downstream mRNA, and is a promising anti-tumor target. Based on the lead compound 1g from previous screening, this study designed and synthesized 52 IGF2BP2 small molecule inhibitors using thiazole hydrazone as the parent nucleus. Among them, 9g, 10g, 37g, 47g and 52g showed good inhibitory activities. This work represents an initial exploration in the development of small molecule inhibitors targeting IGF2BP2, using thiazolehydrazone as the core structure. It lays a foundation for subsequent related research.