Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

BACKGROUND:When cultivating cells with high demand for structure and oxygen,it is necessary to construct a three-dimensional biological scaffold with hollow pipe structure to make sure the cells get enough nutrients and oxygen.In recent years,hydrogel tissue engineering scaffolds with hollow pipe structure have been paid more and more attention.OBJECTIVE:The biological scaffold material based on sodium alginate was combined with coaxial printing technology to prepare a tissue engineering scaffold with a hollow pipe structure,and the cells were inoculated by perfusion to verify its biological properties.METHODS:The sodium alginate-acrylamide mixed printing solution was prepared,and the parameters such as the printing speed of the inner and outer layers in the coaxial printing process,sodium alginate concentration,and calcium chloride concentration in the receiving dish were controlled to realize the printing of the tissue engineering scaffold with a hollow pipe—sodium alginate-polyacrylamide double-crosslinked hydrogel.The microstructure and elastic modulus of the scaffold were characterized.Mouse fibroblasts were injected into hollow pipes of tissue engineering scaffolds.Cell compatibility was observed by living/dead cell staining.RESULTS AND CONCLUSION:(1)By exploring the printing parameters in the printing process,when the inner printing speed was constant,the outer diameter of the hollow pipe increased with the increase of the flow rate of the outer printing solution,and the inner diameter increased slightly.When the flow rate of the outer layer printing solution was constant,and the flow rate of the inner layer solution was increased,the outer diameter of the hollow pipe was basically unchanged,and the inner diameter was significantly improved.(2)Experimental results showed that the concentration of sodium alginate was 2.5%.Excessive concentration was not conducive to the fusion of multi-layer structure layers,and the mechanical properties of hydrogels prepared at too low concentration were insufficient.(3)The elastic modulus of the double-crosslinked hydrogel was higher,generally higher than 200 kPa,and increased with the increase of the concentration of calcium chloride,and reached the maximum value of 375 kPa when the concentration of calcium chloride in the inner layer was 2%and the concentration of calcium chloride in the receiving dish was 0.3%.(4)The staining of live and dead cells after the tissue engineering scaffold perfusion cells in vitro showed that the cells were distributed along the axis of the hollow pipe and had a higher survival rate,but the cell concentration was lower than that during perfusion.(5)The results show that the sodium alginate-polyacrylamide double-crosslinked hydrogel has strong mechanical properties while retaining good biocompatibility,and can be used in the construction of tissue engineering scaffolds with hollow pipes,and the method of"first preparing the scaffold,then inoculating the cells"also avoids the traditional"cells and printing solution are mixed and then prepared"method to limit the scaffold material and processing method.

Objective:To explore the differences in quality of life among patients with olfaction disorders (OD) due to various etiologies and to identify factors influencing olfactory-related quality of life.Methods:This cross-sectional study enrolled patients with OD who visited the Department of Otolaryngology at Fudan University Eye, Ear, Nose, and Throat Hospital between February and June 2024. Psychophysical olfactory test was performed using the Chinese Smell Identification Test (CSIT), which was based on the Chinese population, with the TDI score used as the total score for threshold (T), discrimination (D), and identification (I) tests. The quality of life related to OD was assessed using a brief version of the Questionnaire of Olfactory Disorders (bQOD), which included QOD-P, QOD-Q, and QOD-VAS. Visual analog scales (VAS) was used to rate the degree of subjective decline in olfaction. Statistical analysis was conducted to assess the impact of etiologies, age, gender, onset time, psychophysical olfactory tests, and subjective assessment on olfactory-related quality of life.Results:A total of 419 patients were enrolled, including 220 males and 199 females, with the age of (39.72±14.31) years (range: 5 to 76 years). Among the 419 patients, 380 completed the bQOD and VAS assessment. The results showed that there were intergroup differences in the QOD-P and QOD-Q scores among patients with OD caused by different etiologies ( P values were 0.001 and 0.003, respectively). The QOD-P score was negatively correlated with age ( P<0.05), and positively correlated with the TDI score ( P<0.01). The QOD-Q score was negatively correlated with disease duration ( P<0.05), and positively correlated with the patients′ subjective olfactory decline as assessed by the VAS score ( P<0.01), and had no significant correlation with psychophysical olfactory tests. Female patients had lower QOD-Q scores than male patients ( P<0.05). The QOD-VAS score was positively correlated with the patients′ subjective olfactory impairment ( P<0.01) and showed no significant correlation with psychophysical olfactory tests. Female patients had worse QOD-VAS scores than male patients ( P<0.05). Conclusion:Compared with psychophysical olfactory tests, VAS olfactory scores are more closely related to quality of life. Different etiologies, duration of the disease, and gender also affect olfactory-related quality of life.

This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Objective:To analyze the relationship between 24-hour urinary calcium (24 h UCa) level and the risk of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and all-cause mortality.Methods:In the Chinese Cohort Study of Chronic Kidney Disease, we examined 3 375 patients aged 18-74 years with CKD stages 1-4. Kaplan-Meier survival and Cox proportional hazard regression models were used to test a time-to-event association between levels of 24 h UCa and incidence of ESKD, CVD, and all-cause mortality.Results:During a follow-up of 4.17 (3.37, 5.20) years, 179, 145, 104 and 38 ESKD events occurred in <0.60, 0.60-, 1.20-, ≥2.32 mmol 24 h UCa groups. Higher levels of 24 h UCa (1.20-,≥2.32 mmol) were independently associated with a lower incidence of ESKD events in patients with CKD, with HR (95% CI) of 0.71 (0.54-0.93) and 0.43 (0.29-0.64), respectively. No significant associations with CVD and all-cause mortality endpoints were detected. Conclusion:Among patients with CKD, levels of 24 h UCa displayed an association with the risk of ESKD among patients with CKD stages 1-4.

Objective To investigate the effects of Qizhi Zhoufei Granules on endoplasmic reticulum stress in rats with chronic obstructive pulmonary disease(COPD);To explore its mechanism.Methods COPD rat model was induced by lipopolysaccharide tracheal instillation and smoking.Totally 60 Wistar rats were divided into control group,model group,Bufei Huoxue Capsules group and Qizhi Zhoufei Granules low-,medium-and high-dosage groups using random number table method,with 10 rats in each group.Drug gavage intervention was carried out for the treatment group since the 29th day of modeling,and normal saline was given to the control group and model group for 28 d.Lung function tests were performed,HE staining was used to detect morphology of lung tissue,TUNEL staining was used to detect the degree of apoptosis in lung tissue,RT-qPCR and Western blot were used to detect the endoplasmic reticulum stress and apoptosis related molecular mRNA and protein expression in lung tissue.Results Compared with the control group,the lung function indexes of peak inspiratory flow(PIF),peak expiratory flow(PEF)and minute volume(MV)significantly decreased,and frequency of breathing(F)significantly increased in the model group(P＜0.05);the structural damage of the lung tissue was obvious,the lung injury score and apoptosis rate significantly increased(P＜0.05),the expressions of glucose regulated protein 78(GRP78),protein kinase R-like ER kinase(PERK),C/EBP-homologous protein(CHOP),Caspase-3 and Caspase-9 mRNA were increased(P＜0.05),the protein expressions of GRP78,p-PERK,activating transcription factor 4(ATF4),CHOP,Caspase-3 and Caspase-9 were significantly increased(P＜0.05).Compared with the model group,PIF,PEF and MV significantly increased in Qizhi Zhoufei Granules medium-and high-dosage groups and Bufei Huoxue Capsules group,and F significantly decreased(P＜0.05);the damage in lung tissue was improved,and the lung injury score and cell apoptosis rate significantly decreased(P＜0.05),the mRNA expressions of GRP78,PERK,CHOP,Caspase-3 and Caspase-9 in lung tissue decreased(P＜0.05),and the protein expressions of GRP78,p-PERK,ATF4,CHOP,Caspase-3 and Caspase-9 decreased(P＜0.05).Conclusion Qizhi Zhoufei Granules can prevent cell apoptosis and excessive damage by inhibiting the expression of endoplasmic reticulum stress related factors in COPD rats,thereby promoting unfolded protein response and improving endoplasmic reticulum folding ability,constraining endoplasmic reticulum stress state,and assisting in its regulation.

Objective:To investigate the correlation between statins and contrast-induced acute kidney injury (CI-AKI) and provide a reference basis for clinical practice.Methods:It was a retrospective cohort study. The adult patients were admitted to Peking University First Hospital from January 1, 2018, to December 31, 2020, and received at least one intravascular iodinated contrast administration during hospitalization. The clinical data of the patients were collected. The enrolled patients were divided into statin group and non-statin group according to statin exposure. The exposure of statins was defined as use of any type of statins within 48 hours before iodinated contrast administration. The primary outcome was in-hospital AKI defined as AKI developed after contrast administration and before discharge, with 30 days as the endpoint observation time, and the secondary outcome was post-contrast AKI (PC-AKI) defined as AKI onset within 72 hours after contrast administration. Cox regression model was applied to investigate the correlation between statin prescription prior to contrast administration and clinical outcomes. Pre-specified interaction analysis was conducted to examine modification effect of age, gender, baseline estimated glomerular filtration rate (eGFR), diabetes and the injection method of contrast.Results:Among 10 321 enrolled patients, the age was 63 (54, 71) years old, and 6 274 (60.8%) patients were males. There were 2 372 (23.0%) patients taking statins before the use of iodinated contrast agents, and the person-time incidence rate of in-hospital AKI was 2.5 per 1 000 person-days. The person-time incidence rate of statin users and statin non-users was 3.2 and 2.4 per 1 000 person-days, respectively. Compared with the non-statin group, age, serum creatinine and the proportions of males, admitted to the intensive care unit, lipid metabolism disorder, hypertension, diabetes, cerebrovascular diseases, cardiovascular diseases, using renin-angiotensin- aldosterone inhibitors, using diuretics, using non-steroidal anti-inflammatory drugs, using proton pump inhibitors, iodinated contrast administration via artery, eGFR<60 ml·min -1·(1.73 m 2) -1 were higher, while the proportions of general anesthesia surgery, severe liver diseases and tumors, and eGFR were lower in the statin group (all P<0.05). Among 10 321 patients, 5 867 patients had serum creatinine measurement within 72 hours after iodinated contrast administration, among which 70 patients (4.0 per 1 000 person-days) developed PC-AKI. Multivariate Cox regression analysis showed that statin use was an independent protective factor for in-hospital AKI ( HR=0.65, 95% CI 0.45?0.93, P=0.017) and PC-AKI ( HR=0.44, 95% CI 0.22?0.88, P=0.020). Subgroup analysis showed the significant interaction between diabetes and statin use ( P for interaction=0.039), and the protective effect of statins against in-hospital AKI was only observed in non-diabetic group ( HR=0.45, 95% CI 0.26?0.77). There were no significant differences in subgroups stratified by age, sex, baseline eGFR and the injection method of contrast (all P for interaction>0.05). Conclusions:Statin use prior to iodinated contrast administration is correlated with reduced risks of in-hospital AKI and PC-AKI in hospitalized patients, and the correlation between statin use and in-hospital AKI is more significant in non-diabetic patients. It is suggested that statin use before the application of iodinated contrast agents in hospitalized patients may prevent the occurrence of AKI.

Objective:To investigate the serum sodium level and its fluctuation in patients with hospitalized acquired acute kidney injury (AKI) and explore their impacts on in-hospital mortality.Methods:It was a single-center retrospective study. The adult patients developing hospital-acquired AKI and receiving at least twice serum sodium tests admitted to Peking University First Hospital from January 1, 2018, to December 31, 2020 were included. Dysnatremia included hyponatremia (< 135 mmol/L) and hypernatremia (>145 mmol/L). The patients were divided into hyponatremia group, normal serum sodium group and hypernatremia group, and the differences of clinical data among the three groups were compared. The fluctuation of serum sodium level was evaluated by coefficient of variation. A restricted cubic spline was applied to investigate the association between serum sodium level at AKI onset and mortality. Poisson regression analysis was used to explore the mortality risk of dysnatremia at AKI onset, dysnatremia at admission, and coefficient of variation of serum sodium, respectively.Results:Among the enrolled 1 475 AKI patients, the age was 66.0 (55.0, 78.0) years, and 850 patients (57.6%) were males. The estimated glomerular filtration rate was 77.3 (50.4, 97.6) ml·min -1·(1.73 m 2) -1. The time from admission to AKI onset was 8 (4, 15) days. The incidence of hyponatremia and hypernatremia at admission were 19.6% (289/1 475) and 2.6% (39/1 475), respectively, while the incidence at AKI onset was 24.0% (354/1 475) and 12.7% (188/1 475), respectively. There was statistically significant difference in terms of age, the initial classification distribution of AKI, serum sodium at admission, serum sodium at the occurrence of AKI, the lowest serum sodium at hospitalization, the highest serum sodium at hospitalization, the coefficient of variation of serum sodium, and the proportions of heart failure, stroke, disseminated intravascular coagulation, sepsis, acute respiratory distress syndrome, shock, prerenal causes, circle diuretics and aldosterone antagonists among hyponatremia group, normal serum sodium group and hypernatremia group (all P<0.05). The restricted cubic spline analysis showed a "U"-shaped correlation between serum sodium level at AKI onset and in-hospital mortality. Poisson regression analysis showed that after adjusting for age, gender, number of chronic comorbidities, initial classification of AKI, basal estimated glomerular filtration rate and number of acute disease state, with normal serum sodium as the reference, hyponatremia ( RR=1.56, 95% CI 1.14-2.13) and hypernatremia ( RR=1.71, 95% CI 1.23-2.39) at AKI onset were correlated with an increased risk of in-hospital mortality. Hyponatremia at admission was correlated with an increased risk of in-hospital mortality ( RR=2.13, 95% CI 1.62-2.79), while there was no statistically significant association between hypernatremia and in-hospital mortality ( RR=1.22, 95% CI 0.62-2.44). After further adjusting serum sodium levels at admission and at the occurrence of AKI, the coefficient of variation of serum sodium level was still correlated with an increased risk of in-hospital mortality ( RR=1.23, 95% CI 1.14-1.33). Conclusions:Dysnatremia is common in patients with hospital-acquired AKI. The serum sodium level at AKI onset is correlated with in-hospital death in a "U" shape. Dysnatremia and serum sodium fluctuation are associated with an increased risk of in-hospital mortality.

Objective:To develop a simplified confocal laser endomicroscopy (CLE)-based healing scoring system for assistant diagnosis of deep remission in ulcerative colitis (UC).Methods:CLE images from consecutive UC patients in clinical remission or mild activity and healthy controls undergoing CLE at Peking University First Hospital from January 2017 to December 2019 were retrospectively analyzed. According to the diagnosis of inflammation in intestinal segments in the medical records of UC patients, CLE images were divided into two groups, the involved group (inflamed UC segment) and the control group (segments from healthy individuals and non-inflamed UC segments). CLE features differentiating the groups were identified, and univariable regression analysis was used to obtain indicators related to unhealed histological inflammation (Geboes score>2.0), forming a simplified CLE healing score using the significant indicators, and receiver operator characteristic (ROC) curve was drawn.Results:The study included 53 UC patients and 14 healthy controls, yielding 201 CLE segments (42 healthy, 69 non-inflamed, 90 inflamed). Eight CLE features differed significantly between the involved and the control groups ( P<0.001), including crypt distortion, crypt lumen irregularity, crypt proximity, crypt sparsity, crypt lumen fluorescein leakage, vascular fluorescein leakage, increased vessel diameter, and cellular infiltration. Univariable regression analysis indicated there were 4 indicators related to histological inflammation, including crypt distortion ( P=0.025, OR=3.613, 95% CI:1.174-11.114), crypt lumen irregularity ( P=0.021, OR=4.081, 95% CI: 1.233-13.511), crypt fluorescein leakage ( P=0.011, OR=5.486, 95% CI: 1.468-20.494) and increased vessel diameter ( P=0.002, OR=7.724, 95% CI: 2.062-28.938). These 4 indicators were combined to form a simplified CLE healing score and a ROC curve was plotted with AUC of 0.769 (95% CI:0.654-0.833). The optimal threshold for histological healing was the absence of all four features (score=0), with sensitivity and specificity of 83.1% (59/71) and 42.1% (8/19), respectively. Conclusion:The simplified CLE score demonstrates high sensitivity and correlates positively with histological healing, supporting its utility as an adjunct tool for assessing deep remission in UC.

Objective:To investigate the efficacy of enteral nutrition in preventing bone marrow suppression in patients with nasopharyngeal carcinoma undergoing concurrent radiotherapy and chemotherapy.Methods:The clinical data of 150 nasopharyngeal carcinoma patients undergoing concurrent radiotherapy and chemotherapy treatment in our hospital from Sep 2022 to Sep 2024 were analyzed.They were divided into the conventional group(74 cases)and the enteral nutrition group(76 cases)according to different nutritional intervention plans.The conventional group received conventional nutritional therapy,while the enteral nutrition group received enteral nutrition therapy.The occurrence of bone marrow suppression,blood routine indicators,nutritional status indicators were compared,and quality of life was evaluated with cancer patient quality of life measurement scale(EORTC-QLQ-C30)and compared.Results:The total incidence of bone marrow suppression in the enteral nutrition group was lower than that in the conventional group(P＜0.05),and the degree of bone marrow suppression was milder than that in the conventional group(P＜0.05).At the end of treatment,the enteral nutrition group had higher levels of hemoglobin,granulocytes count,red blood cells count,white blood cells count,platelets count,body mass index,upper arm circumference,waist circumference,and scores of each functional domain of EORTC-QLQ-C30 compared to the conventional group(P＜0.05).Conclusion:Enteral nutrition therapy for nasopharyngeal carcinoma patients undergoing concurrent radiotherapy and chemotherapy can prevent bone marrow suppression,improve blood routine indicators and nutritional status,and enhance quality of life.