Objective To investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

Objective:To evaluate the effect of value orientation brief therapy(VBT)combined with selective serotonin reuptake inhibitors(SSRIs)on clinical symptoms,rumination,decision-making ability,and cognitive func-tion in patients with mild to moderate depression.Methods:Eighty patients meeting the DSM-5 diagnostic criteria for mild to moderate depression were randomly assigned to either a medication(SSRIs)group(36 completed)or a VBT combined group(38 completed)for a 6-week intervention.Baseline and post-intervention assessments includ-ed the Hamilton Depression Scale(HAMD),Hamilton Anxious Scale(HAMA),Ruminative Response Scale-Chi-nese Version(RRS-CV),Iowa Gambling Test(IGT),number of eye fixation(NEF),responsive search score(RSS)in exploratory eye trajectory movement were used to evaluate patients'anxiety and depression symptoms,ru-minative thinking,decision-making function,and cognitive function.Results:The VBT combined group showed sig-nificantly better therapeutic effects than the medication group(P＜0.05).Compared to baseline and the medication group,the VBT combined group had significantly lower post-intervention scores in HAMD,HAMA,symptom rumi-nation,introspective reflection,compulsive meditation,and RRS-CV total scores after intervention(Ps＜0.05),and significantly higher scores in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Compared with the medica-tion group,the VBT combined group demonstrated a greater reduction in HAMD,HAMA,symptom rumination,in-trospective reflection,compulsive meditation,and RRS-CV total scores before and after intervention(Ps＜0.05),and a larger increase in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Conclusion:VBT combined with SSRIs effectively improves the symptoms of depression,anxiety,decision-making ability,rumination thinking,and cognitive function in patients with mild to moderate depression.

Objective:To evaluate the effect of value orientation brief therapy(VBT)combined with selective serotonin reuptake inhibitors(SSRIs)on clinical symptoms,rumination,decision-making ability,and cognitive func-tion in patients with mild to moderate depression.Methods:Eighty patients meeting the DSM-5 diagnostic criteria for mild to moderate depression were randomly assigned to either a medication(SSRIs)group(36 completed)or a VBT combined group(38 completed)for a 6-week intervention.Baseline and post-intervention assessments includ-ed the Hamilton Depression Scale(HAMD),Hamilton Anxious Scale(HAMA),Ruminative Response Scale-Chi-nese Version(RRS-CV),Iowa Gambling Test(IGT),number of eye fixation(NEF),responsive search score(RSS)in exploratory eye trajectory movement were used to evaluate patients'anxiety and depression symptoms,ru-minative thinking,decision-making function,and cognitive function.Results:The VBT combined group showed sig-nificantly better therapeutic effects than the medication group(P＜0.05).Compared to baseline and the medication group,the VBT combined group had significantly lower post-intervention scores in HAMD,HAMA,symptom rumi-nation,introspective reflection,compulsive meditation,and RRS-CV total scores after intervention(Ps＜0.05),and significantly higher scores in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Compared with the medica-tion group,the VBT combined group demonstrated a greater reduction in HAMD,HAMA,symptom rumination,in-trospective reflection,compulsive meditation,and RRS-CV total scores before and after intervention(Ps＜0.05),and a larger increase in IGT net profit scores,NEF,and RSS scores(Ps＜0.05).Conclusion:VBT combined with SSRIs effectively improves the symptoms of depression,anxiety,decision-making ability,rumination thinking,and cognitive function in patients with mild to moderate depression.

Objective The Network Enhancement Fusion(ne-SNF)method had no denoising strategy for the networks from each omics data type,which would weaken the power of network fusion.To address this problem,we proposed an improved Network Enhancement Fusion(improved ne-SNF)model,and further applied the method to subtype identification of papillary renal cell carcinoma.Methods We conducted simulation studies to compare the performances of the improved ne-SNF method with the ne-SNF and SNF method,and applied improved ne-SNF method to integrate multi-omics data of PRCC.Cox regression model was performed to evaluate the prognostic risk of different subtypes.Differentially expressed mRNAs(DEmRNAs),miRNAs(DEmiRNAs)and differentially methylated genes(DMGs)with different subtypes were screened.KEGG pathway analysis was performed for the overlapping genes of three gene sets.Finally,the immune cell infiltration analysis was performed for patients with different subtypes.Results The improved ne-SNF method outperformed both SNF and ne-SNF approach in various simulation scenarios.In subsequent subtyping application,PRCC patients were divided into high-risk and low-risk groups,and the risk of death was 7.727 times higher in the high-risk group than in the low-risk group.A total of 3511 DEmRNAs,96 DEmiRNAs and 3426 DMGs were identified.Among them,649 overlapping genes yielded 42 KEGG pathways with statistical differences.In addition,3 immune filtrating cells showed statistical significance.Conclusion The improved ne-SNF performed better than SNF and ne-SNF,and the identified subtypes of PRCC may provide important clues and basis for treatment of PRCC patient.

Objectives:To investigate the relationship between paraspinal muscle degeneration and isthmic spondylolisthesis in L5/S1.Methods:The clinical data of 108 patients with L5/S1 bilateral isthmic spondylolysis admitted and treated at the Department of Orthopedics,the First Affiliated Hospital of Zhengzhou University from January 1,2020 to December 31,2023 were retrospectively analyzed.There were 62 females and 46 males,aged 26-86(52.8±10.4)years.All the patients had complete imaging data,including lateral and dynamic lumbar X-ray,lumbar CT and lumbar MRI.According to the presence or absence of spondylolisthesis and Meyerding grading,the patients were divided into non-spondylolisthesis group(28 cases),grade Ⅰ spondylolisthesis group(46 cases)and grade n spondylolisthesis group(34 cases).Venebral body cross-sectional area(V CSA),erector spinae muscle cross-sectional area(ES CSA),multifidus muscle cross-sectional area(MF CSA),and facet joint angle(FJA)were measured at the inferior vertebral endplate of L5 vertebral body on the axial view of lumbar spine MRI.And the mean FJA(mFJA),relative MF CSA(MF rCSA),relative ES CSA(ES rCSA),fat infiltration rate of multifidus muscle(MF FIR)and fat infiltration rate of erector spinae muscle(ES FIR)were calculated.The differences in age,gender,body mass index(BMI),disease duration,V CSA,mFJA,MF CSA,ES CSA,MF rCSA,ES rCSA,MF FIR and ES FIR between the three groups were compared.Ordinal logistics regression was used to analyze the relationship between age,gender,disease duration,BMI,mFJA,MF rCSA,ES rCSA,MF FIR,ES FIR and the isthmic spondylolisthesis.Results:There were no statistical differences in age,body weight,BMI,V CSA,and mFJA between the three groups(P＞0.05).The proportion of female patients in the non-spondylolisthesis group(29％)was significantly lower than that in grade Ⅰ spondylolisthesis group(61％)and grade Ⅱ spondylolisthesis group(76％)(P＜0.05).The height of non-spondylolisthesis group(1.68±0.06m)was higher than that of grade Ⅰ spondylolisthesis group(1.64±0.75m)and grade Ⅱ spondylolisthesis group(1.63±0.54m)(P＜0.05),and the disease duration in the non-spondylolisthesis group was shorter than that of grade Ⅰ spondylolisthesis group and grade Ⅱspondylolisthesis group(P＜0.05).There was no significant difference in MF CSA,MF rCSA and ES FIR between the three groups(P＞0.05).ES CSA and ES rCSA in grade Ⅱ spondylolisthesis group(3183.2±1196.38mm2 and 2.14±1.11)were significantly greater than that in grade Ⅰ spondylolisthesis group(2579.28±896.56mm2 and 1.65±0.65)and non-spondylolisthesis group(2401.40±742.98mm2 and 1.56±0.58)(P＜0.05).The MF FIR of grade Ⅱ spondylolisthesis group(40.70±14.05)％was significantly higher than that of grade Ⅰspondylolisthesis group(30.39±12.98)％and non-spondylolisthesis group(26.69±9.96)％(P＜0.05).There were no significant differences in ES CSA,ES rCSA and MF FIR between grade Ⅰ spondylolisthesis group and non-spondylolisthesis group(P＞0.05).Ordinal logistics regression analysis showed that female(OR=2.81;95％CI:1.120-7.062;P=0.028)and increased MF FIR(OR=1.044;95％CI:1.003-1.088;P=0.034)were the independent risk factors for the progression of isthmic spondylolisthesis(P＜0.05).Conclusions:Patients with a higher degree of isthmic spondylolisthesis have more severe fat infiltration of multifidus muscle and hypertrophy of erector spinae muscle.Female and increased MF FIR are independent risk factors for the progression of isthmic spondylolisthesis.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Combined with teaching practice, this study summarizes the teaching contents, methods and effect evaluation of pathological technology for professional postgraduates majoring in pathology. According to the basic conditions of postgraduates, the pathological technology training program has been formulated, student-centered heuristic teaching is carried out by using diversified teaching methods such as flipped classroom, interactive theoretical teaching is carried out by using the intelligent teaching platform, and practical teaching is carried out by using the problem-based learning mode, aiming to improve the theoretical literacy and practical level of pathological technology of professional postgraduates majoring in pathology, improve their clinical research thinking, and lay a foundation for clinical pathological diagnosis and scientific research in the future.

Objective:To investigate the expression of soluble CD40 ligand (sCD40L) in serum of children with Kawasaki disease at acute stage and its diagnostic value in coronary artery disease (CAL).Methods:This study adopts case-control study method. Select 127 children with Kawasaki disease admitted to Xuzhou Children's Hospital affiliated to Xuzhou Medical University from August 2021 to August 2022. They are divided into CAL group and non-CAL group according to the degree of coronary artery involvement. Select 30 healthy children who have physical examination in this hospital at the same time as the healthy control group, and select another 30 children with acute upper respiratory tract infection and fever admitted to this hospital at the same time as the fever control group.Compare the sex, age and laboratory indicators of children with Kawasaki disease with or without CAL, and compare the difference between the serum sCD40L level of children with Kawasaki disease with or without CAL and the fever control group and the healthy control group, the serum sCD40L level of children with different degrees of coronary artery dilation, and analyze the correlation between the serum sCD40L and various laboratory indicators of children with Kawasaki disease and the influencing factors of children with Kawasaki disease complicated with CAL, To evaluate the screening effect of serum sCD40L for Kawasaki disease complicated with CAL. The measurement data with normal distribution is expressed by xˉ± s, the comparison between the two groups adopts independent sample t-test, the comparison between multiple groups adopts one-way ANOVA, and the comparison between two groups adopts LSD method and Bonferroni correction; The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison between the two groups is conducted by Mann-Whitney U test. Pearson method and Spearman mothod were used for correlation analysis. Logistic regression model was used to analyze the influencing factors of children with Kawasaki disease complicated with CAL. The diagnostic value of serum sCD40L level in Kawasaki disease complicated with CAL was analyzed by drawing the ROC curve. Results:All 127 children with Kawasaki disease were divided into CAL group (45 cases) and non-CAL group (82 cases) according to the presence or absence of CAL. The serum level of sCD40L in CAL group was higher than that in non-CAL group, healthy control group and fever control group ((7.03±0.91) μg/L vs (4.66±1.23), (1.73±0.96), (2.21±1.08) μg/L), the difference was statistically significant (all P<0.001). The serum level of sCD40L in children with coronary artery dilation in CAL group was lower than that in children with small CAA, medium CAA and large CAA ((6.04±0.22) μg/L vs (6.95±0.69), (8.02±0.57), (8.23±0.26) μg/L), the difference was statistically significant (all P<0.001). Serum sCD40L level and platelet count (PLT), C-reactive protein (CRP), N-terminal pro brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF-α) in children with Kawasaki disease All were positively correlated ( r=0.31, P<0.001, r=0.32, P<0.001, r=0.26, P=0.003, r=0.58, P<0.001, r=0.27, P=0.002, r=0.39, P<0.001). Serum sCD40L, IL-6 and NT-proBNP were the risk factors of complicated CAL in children with Kawasaki disease (odds ratio 1.21, 1.06 and 1.01, 95% confidence interval 1.03-1.43, 1.01-1.12, 1.00-1.01, P values were 0.022, 0.011 and 0.039, respectively). The area under the curve of serum sCD40L in diagnosing Kawasaki disease complicated with CAL was 0.928 (95% confidence interval: 0.885-0.971), and the optimal critical value was 5.60 μg/L, the sensitivity was 97.8% and the specificity was 79.3%. Conclusions:The level of serum sCD40L increased in children with Kawasaki disease in acute phase, especially in children with CAL. The level of serum sCD40L increased with the severity of CAL, which is a risk factor for Kawasaki disease complicated with CAL, and has certain diagnostic value for Kawasaki disease complicated with CAL.

【Objective】 To evaluate the residual risk of hepatitis C virus (HCV) in blood screening among voluntary blood donors in Zhengzhou. 【Methods】 The ELISA and NAT screening results of 497 171 voluntary blood donors in Zhengzhou from January 2019 to December 2020 were collected through the information management system of our blood center.The residual risk of HCV was assessed using the Prevalence-Window Period Residual Risk Model. 【Results】 The residual risk among repeated and first-time blood donors was 1∶132 280 (95% CI: 1∶95 520~1∶188 820) and 1∶44 090 (95% CI: 1∶31 840~1∶62 940), respectively. The overall residual risk of blood donors screening was 1∶68 540 (95% CI: 1∶65 910~1∶130 290). The reactive rate of HCV screening in first-time blood donors (0.144%, 334/231 168) was significantly higher than that in repeated blood donors (0.014%, 36/266 003) (P<0.05), and the reactive rate of repeated blood donors in 2019 (0.019%, 26/135 267) was significantly higher than that in repeat blood donors in 2020 (0.008%, 10/130 736) (P<0.05). 【Conclusion】 The residual risk of HCV among voluntary blood donors in Zhengzhou is low.The publicity and recruitment should be further strengthened to establish a stable team of voluntary blood donation, and health consultation and physical examination should also be strengthened to further reduce the residual risk of blood transfusion.

Cell Cycle Proteins ; Microtubule-Associated Proteins