Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective:To investigate the predictive value of combined detection of serum microribonucleic acid-30c-5p(miR-30c-5p)and neuroligin-1(NLGN1)for postoperative recur-rence and metastasis in patients undergoing laparoscopic radical resection of colorectal cancer.Methods:A total of 112 colorectal cancer patients who underwent laparoscopic radical resection from August 2021 to August 2022 were regarded as the diseased group.They were separated into a recurrent group(n=28)and a non-recurrent group(n=84)based on whether the patients had recurrence or metastasis within 12 months after surgery.Additionally,92 normal volunteers who underwent physical examinations were as the control group.QRT-PCR was applied to de-tect serum miR-30c-5p and NLGN1 mRNA levels.Multivariate logistic regression was applied to analyze the affecting factors of postoperative recurrence and metastasis in patients.Receiver op-erating characteristic(ROC)curve was plotted to analyze the predictive value of serum miR-30c-5p and NLGN1 mRNA for postoperative recurrence and metastasis in patients.Pearson method was applied to analyze the correlation between miR-30c-5p and NLGN1.Results:The miR-30c-5p level in the diseased group was greatly lower than that in the control group(P＜0.05),and the NLGN1 mRNA level was significantly higher than that in the control group(P＜0.05).Compared with the non recurrent group,the miR-30c-5p level in the recurrent group was significantly re-duced(P＜0.05),while the NLGN1 mRNA level was significantly increased(P＜0.05).There was a statistically significant difference in tissue differentiation between the non-recurrent group and the recurrent group(P＜0.05).Low differentiation of tumor tissues and elevated level of NLGN1 mRNA were risk factors for postoperative recurrence and metastasis(P＜0.05).Elevated level of miR-30c-5p was a protective factor of postoperative recurrence and metastasis(P＜0.05).The AUC of serum miR-30c-5p,NLGN1 mRNA,and their combined prediction for postoperative re-currence and metasta sis in patients was 0.823,0.823,and 0.902,which was greatly better than the individual prediction of miR-30c-5p(Z=2.031,P=0.042)and NLGN1 mRNA(Z=2.239,P=0.025).There was a negative correlation between miR-30c-5p and NLGN1 mRNA levels(r=-0.436,P＜0.05).Conclusion:The dicrease of miR-30c-5p level and increase of NLGN1 mRNA level in laparoscopic colorectal cancer patient has auxiliary predictive value for postoperative recur-rence and metastasis.

The update of multi-omics technology is a key means to promote the rapid development of accurate health model in the whole life cycle.It can formulate dynamic and accurate nursing measures and provide massive data information from the perspective of nursing biology of health and disease.At present,clinical nursing research faces many challenges such as insufficient application and transformation ability of multi-omics technology.This paper introduces the multi-omics technology,reviews the application status of multi-omics technology in cancer nursing,maternal and child nursing,chronic metabolic disease nursing and symptom management,and puts forward the cross integration and prospect of multi-omics technology and nursing research,so as to strengthen the information mining ability of nurses at different levels of health and disease,and provide an important basis for accelerating the clinical transformation of precision nursing.

Objective: To investigate the influence of reactive oxygen species (ROS) responsive self-assembled nanomicelle loaded with pyroptosis inhibitor on full-thickness skin defects in diabetic rats. Methods: Experimental research methods were employed. A nucleotide-binding oligomerization domain (NOD) 1/2 inhibitor (NOD-IN-1) was encapsulated with nanomicelle polyethylene glycol-block-polypropylene sulfide (PEG-b-PPS), and the resulting product was called PEPS@NOD-IN-1. The morphology and hydration particle size of PEG-b-PPS and PEPS@NOD-IN-1 were observed by transmission electron microscope and particle size analyzer, respectively, and the encapsulation rate and drug loading rate of PEPS@NOD-IN-1 to NOD-IN-1 and the cumulative release rate of NOD-IN-1 by PEPS@NOD-IN-1 in phosphate buffer solution (PBS) alone and hydrogen peroxide-containing PBS within 40 h were measured and calculated by microplate reader, and the sample number was 3. Twenty-four male Sprague-Dawley rats aged 6-7 weeks were injected with streptozotocin to induce type 1 diabetes mellitus. Six full-thickness skin defect wounds were made on the back of each rat. The injured rats were divided into PBS group, NOD-IN-1 group, PEG-b-PPS group, and PEPS@NOD-IN-1 group with corresponding treatment according to the random number table, with 6 rats in each group. The wound healing was observed on post injury day (PID) 3, 7, and 12, and the wound healing rate was calculated. The ROS levels in wound tissue were detected by immunofluorescence method on PID 3. On PID 7, the granulation tissue thickness in wound was assessed by hematoxylin-eosin staining, the mRNA expressions of NOD1 and NOD2 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction, and the protein expressions of NOD1, NOD2, and GSDMD-N terminals were detected by Western blotting. Six wounds from different rats in each group were taken for detection of the above indicators. Wound tissue (3 samples per group) was taken from rats in PBS group and PEPS@NOD-IN-1 group on PID 7, and transcriptome sequencing was performed using high-throughput sequencing technology platform. Differentially expressed genes (DEGs) significantly down-regulated in PEPS@NOD-IN-1 group as compared with PBS group were screened, and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. The DEG heatmap of the NOD-like receptor pathway, a pyroptosis-related pathway, was made. Protein-protein interaction (PPI) analysis of DEGs in heatmap was performed through the STRING database to screen key genes of PEPS@NOD-IN-1 regulating the NOD-like receptor pathway. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and Tukey test. Results: PEG-b-PPS and PEPS@NOD-IN-1 were in spherical structures of uniform size, with hydration particle sizes of (134.2±3.3) and (143.1±2.3) nm, respectively. The encapsulation rate of PEPS@NOD-IN-1 to NOD-IN-1 was (60±5)%, and the drug loading rate was (15±3)%. The release of NOD-IN-1 from PEPS@NOD-IN-1 in PBS alone was slow, and the cumulative release rate at 40 h was only (12.4±2.3)%. The release of NOD-IN-1 from PEPS@NOD-IN-1 in hydrogen peroxide-containing PBS within 10 h was very rapid, and the cumulative release rate at 10 h reached (90.1±3.6)%. On PID 3 and 7, the wounds of rats in the four groups were gradually healed, and the healing in PEPS@NOD-IN-1 group was better than that in the other three groups. On PID 12, the wound scab area in PBS group was large, the wound epithelialization in NOD-IN-1 group and PEG-b-PPS group was obvious, and the wound in PEPS@NOD-IN-1 group was close to complete epithelialization. Compared with those in PBS group, NOD-IN-1 group, and PEG-b-PPS group, the wound healing rates on PID 7 and 12 in PEPS@NOD-IN-1 group were significantly increased (P<0.05), the level of ROS in wound tissue on PID 3 was significantly decreased (P<0.05), the thickness of granulation tissue in wound on PID 7 was significantly thickened (P<0.05), and the mRNA expressions of NOD1 and NOD2 and the protein expressions of NOD1, NOD2, and GSDMD-N terminals in wound tissue on PID 7 were significantly decreased (P<0.05). KEGG pathway analysis showed that DEGs significantly down-regulated in PEPS@NOD-IN-1 group as compared with PBS group were significantly enriched in NOD-like receptors, hypoxia-inducible factors, mitogen-activated protein kinases, and tumor necrosis factor (TNF) pathways. In the DEG heatmap of NOD-like receptor pathway, the genes regulating pyroptosis mainly involved NOD1, NOD2, NOD-like receptor thermoprotein domain-related protein 3, Jun, signal transduction and transcriptional activator 1 (STAT1), TNF-α-induced protein 3. The PPI results showed that NOD1, NOD2, and STAT1 were the key genes of PEPS@NOD-IN-1 regulating the NOD-like receptor pathway. Conclusions: PEPS@NOD-IN-1 can down-regulate the level of local ROS in wounds and the expression of NOD1, NOD2, and GSDMD-N terminals, the key regulators of pyroptosis, thereby promoting the repair of full-thickness skin defect wounds in diabetic rats. PEPS@NOD-IN-1 can also significantly down-regulate the pyroptosis, inflammation, and hypoxia-related pathways of wounds, and regulate NOD-like receptor pathways by down-regulating key genes NOD1, NOD2, and STAT1.
Rats ; Male ; Animals ; Reactive Oxygen Species ; Wound Healing ; Rats, Sprague-Dawley ; Diabetes Mellitus, Experimental ; Hydrogen Peroxide ; Pyroptosis ; Skin Abnormalities ; Soft Tissue Injuries ; NLR Proteins ; Hypoxia ; RNA, Messenger

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.
Polyethylene Glycols/chemistry* ; Castor Oil ; Methanol ; Surface-Active Agents/chemistry* ; Solvents ; Water/chemistry* ; Emulsions/chemistry*

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.
Awareness ; Brain ; Consciousness ; Humans ; Oxygen ; Visual Perception

ObjectiveTo optimize the extraction and purification process of Gardeniae Fructus for industrial production， and to obtain the total iridoid and total crocin extracts. MethodOrthogonal test was used to optimize the water extraction process by taking contents of geniposide， genipin gentiobioside， gardenoside， crocin-1 and crocin-2 as indicators and the decocting time， decocting times and water amount as factors. The purification process was optimized by single factor test， and four different types of macroporous adsorption resins were screened. The process conditions such as resin type， maximum loading amount， water washing amount， ethanol concentration， ethanol dosage， and flow rate of sample loading were mainly investigated. In addition， the drying methods （vacuum drying and spray drying） of the extract were investigated， and a pilot scale-up verification test was carried out. ResultThe optimal water extraction process of Gardeniae Fructus was to add 15， 10 times the amount of water for decocting twice， 1 h each time. The optimal purification process was as follows：the water extract through SP825L macroporous resin column， the amount of crude drug-the amount of resin （1∶1.5）， the sample loading flow rate of 3 BV h^-1， adding 2 BV of water to remove impurities， adding 4 BV of 30% ethanol to obtain the iridoid part， then adding 3 BV of 70% ethanol to obtain the crocin part， collecting the ethanol lotion， and drying at 70 ℃. Under these conditions， the extraction amount of total iridoids was 590.75 mg·g^-1 with the transfer rate of 70.48%， and the yield of dry extract was 8.89%. The extraction amount of total crocins was 83.37 mg·g^-1 with the transfer rate of 22.20%， and the dry extract yield was 2.60%. ConclusionThe optimized extraction and purification process is stable and feasible with high extraction rate of active components， which is suitable for the industrial extraction and purification of active parts of Gardeniae Fructus.

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 μg·mL~(-1) and 0.66 μg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.
Antineoplastic Agents, Phytogenic/pharmacology* ; Cell Line, Tumor ; Drug Carriers ; Female ; Folic Acid ; Glycolates ; HeLa Cells ; Humans ; Micelles ; Paclitaxel ; Particle Size ; Uterine Cervical Neoplasms/drug therapy*