Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.

Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.

Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Objective To investigate the feasibility of energy spectrum CT material separation technology for quantitative evaluation of nonalcoholic fatty liver patients,to compare the accuracy of this method with the conventional liver/spleen CT ratio for grading liver fat content.Methods Sixty patients diagnosed with nonalcoholic fatty liver and 20 healthy volunteers were chosen to undergo liver MR multi-echo(ME)Dixon and energy spectrum CT scans.The proton density fat fraction(PDFF),fat concentration(FC),and liver/spleen CT ratio were then measured for each participant.According to PDFF,nonalcoholic fatty liver patients were divided into mild fatty liver group,moderate fatty liver group,and severe fatty liver group.Results With the increase in PDFF,FC increased and the liver/spleen CT ratio decreased.The difference between FC groups in normal,mild,moderate and severe fatty liver groups was statistically significant(P<0.05),while the difference between the liver/spleen CT ratio of normal group and mild fatty liver group was not statistically significant(P>0.05).The receiver operating characteristic(ROC)curve analysis showed that when the critical value of FC was 351.19 mg/mL,the sensitivity,specificity and area under the curve for normal group and fatty liver group were 0.95,0.1 and 0.99,respectively.Conclusion The energy spectrum CT material separation technology has a good correlation between the fat content measured by the MR ME Dixon,which is superior to the fat content measured by the liver/spleen CT ratio.For patients with nonalcoholic fatty liver,FC in energy spectrum CT has high accuracy in differentiating normal and mild fatty liver.

Objective To explore the application value of functional movement screening(FMS)and targeted physical fitness training in military training for armored troops in cold area.Methods A total of 160 male new recruits were selected from an armored synthetic brigade by random number table method,and then divided into the experimental group and the control group(n=80).The common subjects in the military training program were given to the control group.Besides the common subjects,the experimental group were also given targeted physical fitness training,including core strength training and targeted movement correction training.Before and in 6 months after training,FMS test was carried out for the 2 groups.The occurrence of training injuries were observed and recorded in 2 groups during the 6 months of new training.Results Before the new training,there was no statistical difference in the FMS score between the experimental group and the control group(15.64±2.95 vs 15.67±3.42,P＞0.05).After 6 months of training,the FMS score of the experimental group was 18.33±2.67,which was significantly higher than that of the control group(16.75±3.31,P＜0.05).The overall incidence of training injury was 12.50％in the experimental group,which was significantly lower than that in the control group,but no significant difference.In both groups,the incidence of training injury was significantly higher in those with FMS score＜14 than those with the score≥14 from the same group(P＜0.05).The incidence in the experimental group with FMS score＜14 was 23.53％(4/17),significantly lower than that in the control group with FMS score＜14[64.29％(9/14),P＜0.05].Conclusion Application of FMS is conducive to understanding and judging the fundamental movements in officers and soldiers,and targeted physical fitness correction training can enhance their own physical quality and reduce the occurrence of training injuries.

OBJECTIVE Notoginseng Radix et Rhizoma residues were used as raw material to compare the difference in the im-pact of different probiotics and composite probiotic on various indicator components through probiotic fermentation,aiming to explore the optimal fermentation process.METHODS The fermentation process was optimized using single factor and Box-Behnken response surface methodology,and the antioxidant capacity of the fermentation product was assessed through in vitro antioxidant experiments.RESULTS The results showed the optimum fermentation processes were 48 h of aerobic fermentation,36 h of anaerobic fermentation,ratio of 2∶3∶1 for Streptococcus thermophilus,Bifidobacterium bifidum and Lactobacillus acidophilus,solid-liquid ratio of 0.14 g·mL-1,inoculation quantity 5%,fermentation temperature 33℃.Under the optimal fermentation conditions,the content of neutral polysaccharide,acidic polysaccharide,and total flavonoid in Notoginseng Radix et Rhizoma residue increased by 105.64%,96.98%and 123.83%,respectively,which were high than those single-strain fermentation.The IC50 values of scavenging DPPH and ABTS free radicals in the fermentation products were 1.774 mg·mL-1 and 3.065 mg·mL-1,respectively,and the power of reducing Fe3+was 0.138 mmol FeSO4 g-1.The antioxidant capacity was significantly enhanced compared to the unfermented residues.CON-CLUSION The optimum fermentation process can significantly elevate the content of indicator components in Notoginseng Radix et Rhizoma residues and enhance its antioxidant capacity.Compared to single-strain fermentation,the content of various indicator compo-nents is significantly increased,showing no apparent antagonistic effect among the probiotics mentioned above.The study provides sci-entific evidence and data support for the resource utilization of Notoginseng Radix et Rhizoma residues.

Objective To investigate the impact of ultra-low dose CT(ULDCT)scanning combined with deep learning image reconstruction(DLIR)on quantitative analysis of pulmonary nodules using computer aided diagnostic system(CAD).Methods Fifty-six further consultation patients with pulmonary nodules were prospectively enrolled.ULDCT and standard-dose CT(SDCT)were performed.The raw ULDCT images were reconstructed using adaptive statistical iterative reconstruction-V40%(ASIR-V40%)and high-strength DLIR(DLIR-H)to obtain ULDCT-ASIR-V40%(group A)and ULDCT-DLIR-H(group B)images,while SDCT images were reconstructed with ASIR-V40%to obtain SDCT-ASIR-V40%(group C)images.Pulmonary nodules with long diameter of 4-30 mm were selected as the target nodules based on reconstructed images.The nodules were divided into solid nodules,calcified nodules and non-solid nodules by 2 physicians.CAD software was used to evaluate the classification of nodules based on 3 groups of images,and the long diameter,transverse diameter,density,volume and malignant risk were quantitatively analyzed.Results Totally 104 target nodules were selected,including 51 solid nodules,26 calcified nodules and 27 non-solid nodules according to physicians.CAD classified 53 solid,24 calcified and 27 non-solid nodules based on group A and B,while based on group C,CAD classification was consistent with that of physicians'.Compared with group C,the density of solid and calcified nodules,the volume and malignant risk of non-solid nodules judged by CAD in group A decreased,so did the density of calcified nodules in group B(all P＜0.05).No significant difference of the other CAD quantitative parameters of nodules was found among 3 groups(all P＞0.05).Conclusion ULDCT scanning combined with DLIR might underestimate the density of calcified pulmonary nodules judged by CAD,but had no significant impact on the other CAD quantitative parameters.

Objective:To investigate the features and influencing factors of language in children with various types of speech disorders.Methods:A case-control study was carried out, 262 children with speech disorder had been diagnosed at the language-speech clinic of the Center of Children′s Healthcare, Children′s Hospital, Capital Institute of Pediatrics from January 2021 to November 2023, the children with speech sound disorder as the speech sound disorder group, the children with developmental stuttering as the stuttering group. There were 100 typically-developed children who underwent physical checkups at the Center of Healthcare during the same period as the healthy group. All children experienced a standardized evaluation of language with diagnostic receptive and expressive assessment of mandarin‐comprehensive(DREAM-C) and questionnaire, One-way ANOVA and LSD test were conducted to compare the differences in overall language, receptive language, expressive language, semantics, and syntax scores among 3 groups of children. According to the results of DREAM-C, the children with speech disorder were divided into language normal group and language delay group. Chi‐square test and multivariate Logistic regression were implemented to analyze the association between the linguistic development of children with speech disorder and potential influential factors.Results:There were 145 children in the speech sound disorder group, including 110 males and 35 females respectively, with an age of (5.9±1.0) years; 117 children in the stuttering group, including 91 males and 26 females, with an age of (5.8±1.0) years; 100 children in the healthy group, including 75 males and 25 females, with an age of (5.7±1.2) years. The variations in overall language, expressive language, and syntax scores among 3 groups of children were statistically significant (92±18 vs.96±11 vs. 98±11, 81±18 vs. 84±14 vs. 88±13, 87±16 vs. 89±11 vs. 91±10, F=5.46, 4.69, 3.68, all P<0.05). Pairwise comparison revealed that the speech sound disorder group had lower scores in overall language, expressive language, and syntactic compared to the healthy group, and the differences were statistically significant (all P<0.01) and the overall language score was lower than that of children with stuttering ( P<0.05). In terms of overall language and expressive language, there was a statistically significant difference in the incidence of language delay among the three groups of children (15.9% (23/145) vs. 20.5% (24/117) vs. 7.0% (7/100), 46.2% (67/145) vs. 39.3% (46/117) vs. 26.0% (26/100); χ2=7.93, 10.28; both P<0.05). In terms of overall language, the stuttering group took up the highest proportion. In terms of expressive language, the speech sound disorder group accounted for the highest amount. The incidence of language delay in children with speech disorder was 44.3% (116/262). Non-parent-child reading, daily screen time ≥1 hour and screen exposure before 1.5 years of age are risk factors for the development of language in children with speech disorder ( OR=1.87, 2.18, 2.01; 95% CI 1.07-3.27, 1.23-3.86, 1.17-3.45; all P<0.01). Negative family history are protective factors for the progress of language ability ( OR=0.37, 95% CI 0.17-0.81, P<0.05). Conclusions:Children with speech disorder tend to have easy access to language delay, especially in expressive language and syntax. The occurrence of language delay in children with speech disorder is tightly connected with factors such as the family medical history, parent-child reading, screen time, etc. Attention should be paid to the development of language in children who suffer from speech disorder.