Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

OBJECTIVE: To detect and analyze the expression and clinical significance of long non-coding RNA tyrosine kinase non-catalytic region adaptor protein 1-antisense RNA1 (NCK1-AS1) in patients with acute myeloid leukemia (AML). METHODS: 89 AML patients and 23 healthy controls were included from the People's Hospital Affiliated to Jiangsu University. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of NCK1-AS1 and NCK1 in bone marrow samples. The relationship between the expression of NCK1-AS1 and the clinical characteristics of patients were analyzed, as well as the correlation between NCK1-AS1 and NCK1. RESULTS: The expression level of NCK1-AS1 in all AML, non-M3 AML and cytogenetically normal AML (CN-AML) patients was significantly higher than that in the control group (P < 0.01, P < 0.05, P < 0.01, respectively). In non-M3 AML, patients with high NCK1-AS1 expression had a significantly lower hemoglobin level than those with low NCK1-AS1 expression (P =0.036), furthermore, NCK1-AS1 ^high patients had shorter overall survival than NCK1-AS1^low patients (P =0.0378). Multivariate analysis showed that NCK1-AS1 expression was an independent adverse factor in patients with non-M3 AML ( HR =2.392, 95% CI :1.089-5.255, P =0.030). In addition, NCK1 expression was also significantly upregulated in all AML, non-M3 AML and CN-AML patients compared with controls (P < 0.01, P < 0.01, P < 0.001, respectively). There was a certain correlation between NCK1-AS1 and NCK1 expression (r =0.37, P =0.0058). CONCLUSION High expression of NCK1-AS1 in AML indicates poor prognosis of AML patients.
Humans ; Leukemia, Myeloid, Acute/genetics* ; RNA, Long Noncoding/genetics* ; Oncogene Proteins/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Prognosis ; Male ; Female ; Middle Aged ; Adult ; Case-Control Studies ; Clinical Relevance

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

In this study,a sensitive lateral flow immunoassay(LFIA)platform based on carbon dots-mesoporous silica nanocomposite(CD-MSNs)fluorescent probes was constructed for high-performance detection of inflammatory marker interleukin-6(IL-6).Green fluorescent carbon dots(CDs)were prepared by hydrothermal method with 3,9-perylenic acid and 3-aminopropyltriethoxysilane(APTES)as raw materials,and highly fluorescent CD-MSNs composites were then constructed by encapsulating the prepared CDs in mesoporous silica nanoparticles(MSNs).Fluorescent probes were prepared by covalent coupling of CD-MSNs with IL-6 antibody.Fluorescent immunochromatographic test strips were constructed by spraying IL-6 capture antibody and goat anti-mouse IgG on nitrocellulose membrane as detection line(T-line)and quality control line(C-line),respectively.The fluorescence immunoassay analyzer was used to quantitatively detect the fluorescence intensity of T-line,and the experimental results showed that the LFIA platform based on this probe had a good linear relationship in IL-6 concentration range of 102-106 pg/mL,and the detection limit was 64 pg/mL,which was two orders of magnitude more sensitive than that of the traditional colloidal gold test strips.This method effectively solved the issue of insufficient sensitivity of traditional LFIA technique,and provided a rapid and highly sensitive detection method for early diagnosis of inflammatory diseases.

Objective:To investigate the role and potential mechanism of m 6A demethylase ALKBH5 in esophageal squamous cell carcinoma (ESCC) . Methods:Real time fluorogenic quantitative PCR and Western blotting were used to detect ALKBH5 expression in normal esophageal epithelial cells (Het-1A) and ESCC cell lines (Eca109, KYSE30, KYSE150, KYSE410). Transient cell lines with overexpression/knockdown of ALKBH5 (siRNA transfection was divided into si-ALKBH5-1 group and si-ALKBH5-2 group) and control cell lines were constructed. The effects of ALKBH5 on ESCC cell proliferation, migration and apoptosis were studied by MTT assay, cell scratch assay and cell apoptosis assay respectively. The differentially expressed gene was screened by the intersection of RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) techniques, and the effect of ALKBH5 on the gene expression was detected by RT-qPCR.Results:Real time fluorogenic quantitative PCR results showed that, the relative expression levels of ALKBH5 RNA in Het-1A, Eca109, KYSE30, KYSE150 and KYSE410 were 1.03±0.28, 0.46±0.02, 0.23±0.10, 0.04±0.02, 0.05±0.00, respectively, with a statistically significant difference ( F=444.60, P<0.001). Western blotting showed that, the relative expression levels of ALKBH5 protein in Het-1A, Eca109, KYSE30, KYSE150 and KYSE410 were 1.14±0.03, 0.88±0.04, 0.66±0.01, 0.69±0.01, 0.95±0.01, respectively, with a statistically significant difference ( F=139.90, P<0.001). MTT test showed that the absorbance ( A) values of KYSE30 control group and ALKBH5 overexpression group were 0.86±0.01 and 1.25±0.01 after 72 hours, respectively, with a statistically significant difference ( t=46.93, P<0.001). The A values of KYSE150 control group and ALKBH5 overexpression group were 1.00±0.03 and 1.43±0.02 after 72 hours, respectively, with a statistically significant difference ( t=16.80, P<0.001). The A values of KYSE30 control group, si-ALKBH5-1 group and si-ALKBH5-2 group were 0.98±0.01, 0.85±0.02 and 0.80±0.09 after 96 hours, respectively, with a statistically significant difference ( F=72.97, P<0.001). The A values of KYSE30 control group were higher than those of si-ALKBH5-1 and si-ALKBH5-2 groups (both P<0.001). The A values of KYSE410 control group, si-ALKBH5-1 group and si-ALKBH5-2 group were 1.28±0.02, 1.15±0.02 and 1.08±0.05 after 72 hours, respectively, with a statistically significant difference ( F=16.97, P=0.003). The A values in KYSE410 control group were higher than those in si-ALKBH5-1 group and si-ALKBH5-2 group ( P=0.020; P=0.003). The cell scratch test showed that 48 hours after scratch, the migration rates of KYSE30 cells in control group and ALKBH5 overexpression group were (27.39±0.54) % and (48.89±5.12) %, respectively, with a statistically significant difference ( t=5.90, P=0.004). The migration rates of KYSE150 cells in control group and ALKBH5 overexpression group were (39.67±0.43) % and (62.20±0.60) %, respectively, with a statistically significant difference ( t=43.15, P<0.001). The migration rates of KYSE30 cells in control group, si-ALKBH5-1 group and si-ALKBH5-2 group were (25.08±1.86) %, (18.75±1.59) % and (7.67±0.52) %, respectively, with a statistically significant difference ( F=74.28, P<0.001). The migration rates of KYSE30 cells in control group were higher than those of si-ALKBH5-1 group and si-ALKBH5-2 group ( P=0.010; P<0.001). The migration rates of KYSE410 cells in control group and si-ALKBH5-1 group, si-ALKBH5-2 group were (38.70±0.41) %, (28.27±1.01) % and (19.40±0.47) %, respectively, with a statistically significant difference ( F=400.20, P<0.001). The migration rates of KYSE410 cells in control group were higher than those of si-ALKBH5-1 group and si-ALKBH5-2 group (both P<0.001). Apoptosis test showed that the apoptosis rates of KYSE30 cells in control group and ALKBH5 overexpression group were (9.59±0.88) % and (4.81±0.89) %, respectively, with a statistically significant difference ( t=6.23, P=0.006). The apoptosis rates of KYSE150 cells in control group and ALKBH5 overexpression group were (8.36±0.09) % and (6.42±0.19) %, respectively, with a statistically significant difference ( t=12.90, P<0.001). The apoptosis rates of KYSE30 cells in control group, si-ALKBH5-1 group and si-ALKBH5-2 group were (4.31±0.19) %, (5.72±0.30) % and (8.94±0.71) %, respectively, with a statistically significant difference ( F=53.46, P<0.001). The apoptosis rates in KYSE30 cells in control group were lower than those in si-ALKBH5-1 group and si-ALKBH5-2 group ( P=0.049; P<0.001). The apoptosis rates of KYSE410 control group, si-ALKBH5-1 group and si-ALKBH5-2 group were (4.45±0.36) %, (5.40±0.11) % and (6.64±0.15) %, respectively, with a statistically significant difference ( F=43.36, P<0.001). The apoptosis rates in KYSE410 cells in control group were lower than those in si-ALKBH5-1 group and si-ALKBH5-2 group ( P=0.016; P<0.001). The differentially expressed gene IGF2BP3 was screened by the intersection of RNA-seq and MeRIP-seq techniques, and the RT-qPCR results showed that, the relative expression levels of IGF2BP3 in KYSE30 were 1.01±0.10 and 1.41±0.10 in control group and ALKBH5 overexpression group, respectively, with a statistically significant difference ( t=4.06, P=0.015). The relative expression levels of IGF2BP3 in KYSE150 were 1.00±0.10 and 1.94±0.24 in control group and ALKBH5 overexpression group, respectively, with a statistically significant difference ( t=5.08, P=0.007). The relative expression levels of IGF2BP3 in KYSE410 were 1.01±0.14, 0.67±0.04 and 0.41±0.04 in control group, si-ALKBH5-1 group and si-ALKBH5-2 group, respectively, with a statistically significant difference ( F=24.36, P=0.001). The relative expression levels of IGF2BP3 in KYSE410 control group were higher than those in si-ALKBH5-1 group and si-ALKBH5-2 group ( P=0.017; P=0.001) . Conclusions:ALKBH5 is underexpressed in ESCC cell lines, but the overexpression of ALKBH5 can promote the proliferation and migration of ESCC cells and inhibit cell apoptosis, which may be related to some negative feedback regulation mechanism. IGF2BP3 may be the downstream target of ALKBH5.

AIM To investigate the protective effects of verbascoside on D-galactose-induced liver injury in mice and its underlying mechanisms.METHODS C57BL/6J mice were randomly assigned to the normal group,the model group,the vitamin E group(100 mg/kg),and the low-dose and high-dose verbascoside groups(40,80 mg/kg),with 10 mice in each group.Simultaneous administration of medicine and subcutaneous injection of D-galactose(600 mg/kg)went on among the groups except the normal group for 8 weeks.Serum ALT,AST,ALP activities,along with TBil levels were measured using biochemical kits.Hepatic GSH,MDA concentrations,as well as SOD and GSH-Px activities were quantified.Liver pathological morphology was evaluated by HE staining,while hepatic fibrosis area was assessed using Sirius red staining.Western blot analysis determined hepatic expression of IL-6,IL-1β,TNF-ɑ,TLR4,NF-κB p65,IκBɑ and p-IKBɑ proteins.RESULTS Compared to the model group,the groups treated with vitamin E or verbascoside demonstrated significantly reduced body weight(P＜0.05,P＜0.01);increased hepatic index(P＜0.05,P＜0.01);decreased serum activities of ALT,AST and ALP alongsided reduced TBil levels(P＜0.05,P＜0.01);attenuated pathological damage of liver tissue and fibrosis severity;reduced hepatic MDA level(P＜0.05,P＜0.01);and elevated GSH level with enhanced SOD and GSH-Px activities(P＜0.05,P＜0.01).Furthermore,the high-dose verbascoside group showed significantly decreased hepatic expressions of IL-6,IL-1 β,TNF-ɑ,TLR4,NF-κB p65,and p-IKBɑ/IKBɑ proteins(P＜0.05,P＜0.01).CONCLUSION Verbascoside improves D-galactose-induced liver injury through its antioxidant activity,anti-inflammatory effects,and suppression of the TLR4/NF-κB signaling pathway.

Objective To investigate the predictive value of bone metabolism parameters on cardiac autonomic nervous system function in patients with type 2 diabetes mellitus(T2DM).Methods A total of 328 patients with T2DM hospitalized in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2022 to October 2023.According to the serum 25(OH)D level,all the participants were divided into<10 ng/ml group(n=80),10～20 ng/ml group(n=173),and 20～30 ng/ml group(n=75).Biochemical indicators,bone metabolic parameters,left ventricular mass(LVM)and left ventricular mass index(LVMI)were compared.Time domain indicators ofheart rate variability(HRV)in 24 h holter electrocardiogram,including the global standard deviation of normal sinus RR interval(SDNN),sinus RR interval mean standard deviation(SDANN),and normal continuous sinus RR interval difference root mean square(RMSSD).Meanwhile,adjacent RR interval difference>50 ms as a percentage of the total inter-period(PNN50),HRV triangle index,standard deviation of the difference between the length of the entire adjacent NN interperiod(SDSD),and 24 h holter electrocardiogram HRV time-domain relevant indicators were compared among the three groups.The influence of bone metabolism parameters on cardiac autonomic nervous function and their correlation were analyzed,and the optimal cutting point of cardiac autonomic nervous function was predicted by receiver operating characteristic(ROC)curve.Results SBP,heart rate(HR),FPG,PWV,PTH and β-CTX in groups of 10 ng/ml,10～20 ng/ml and 20～30 ng/ml decreased in turn(P<0.05),while HDL-C,ABI,25(OH)D,Ca2+and PNN50 decreased.Correlation analysis between Spearman and Pearson showed that 25(OH)D was positively correlated with SDNN,HRV triangle index,PNN50 and rMSSD(P<0.01).Logistic regression analysis showed that 25(OH)D,Ca2+and HR were the influencing factors of cardiac autonomic nervous dysfunction in patients with T2DM.The ROC curve analysis showed that the areas under the ROC curve of 25(OH)D,Ca2+and HR were 0.791,0.607 and 0.629,respectively,with sensitivity of 73.4%,53.2%and 38.7%,and specificity of 74.0%,93.6%and 81.4%,respectively.Conclusions 25(OH)D is the influencing factor of cardiac autonomic nervous dysfunction in patients with T2DM,and patients with high degree of deficiency are more prone to cardiac autonomic nervous dysfunction.

Objective: To evaluate the effect of exercise prescription intervention among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for guiding appropriate physical activity and glycemic control in this population. Methods: In July 2023, T2DM patients managed by two community health service centers in Qingjiangpu District, Huai'an City, Jiangsu Province, were selected as the study participants and randomly assigned divided into a control group and an intervention group. The control group received routine chronic disease management under the basic public health services, while the intervention group, in addition to receiving the same routine chronic disease management, was provided with exercise prescription to guide their physical activity at baseline (T0), after 3 months of intervention (T1), and after 6 months of intervention (T2). Data on weight-related indicators, glycated hemoglobin (HbA1c), and blood lipid were collected through physical examinations and laboratory tests at T0 and after 12 months of intervention (T3). The differences in indicators between the two groups before and after the intervention were analyzed using generalized estimating equations. Results: The intervention group consisted of 197 patients, including 99 males, accounting for 50.25%. The median disease duration was 7.10 (interquartile range, 7.80) years, and 113 patients had suboptimal HbA1c levels, accounting for 57.36%. The control group included 196 patients, including 99 females, accounting for 50.51%. The median disease duration was 6.10 (interquartile range, 7.00) years, and 100 patients had suboptimal HbA1c levels, accounting for 51.02%. Before the intervention, no statistically significant differences were observed between the two groups in gender, educational level, disease duration, pharmacological treatment, smoking, alcohol consumption, and HbA1c levels (all P>0.05). In the intervention group, the proportion of participants engaging in aerobic exercise and strength training increased from 78.17% and 8.12% at T0 to 85.79% and 16.24% at T3, respectively (both P<0.05). The results of the generalized estimating equations revealed significant interactions between group and time for waist-to-hip ratio, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) following the intervention (all P<0.05). A statistically significant difference in waist-to-hip ratio was found between the two groups (P<0.05), with a greater reduction observed in the intervention group compared to the control group. Significant differences in TC and LDL-C levels were noted across different intervention time points (both P<0.05). Specifically, the intervention group demonstrated reductions of 0.35 mmol/L in TC and 0.42 mmol/L in LDL-C from baseline to follow-up (both P<0.05). Conclusion The 12-month exercise prescription intervention can effectively enhance exercise participation and reduce waist-to-hip ratio, TC, and LDL-C levels among patients with T2DM.

Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P＜0.05,P＜0.01).The levels of WBC and NE in the model-A increased significantly(P＜0.01).The level of LY in model-B decreased significantly(P＜0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P＜0.01).The levels of IL-6 in model-A and model-B were significantly increased(P＜0.05,P＜0.01).The collagen volume fraction of model-A and model-B were significantly increased(P＜0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P＜0.01),and the expression levels of IκBα/β-actin were significantly decreased(P＜0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P＜0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.