Objective:To investigate the effect of tripartite motif-containing protein 59 (TRIM59) on glucose metabolism in macrophages and its role in regulating hypoxia-inducible factor-1α (HIF-1α)/IL-10 axis in macrophages under inflammatory conditions.Methods:The differentially expressed genes between macrophages with high expression of TRIM59 and control cells transfected with empty TRIM59 plasmid were analyzed by GO and KEGG. The expression of HIF-1α by RAW264.7 macrophages with high expression of TRIM59 was detected at different time points after lipopolysaccharide (LPS) stimulation by RT-qPCR and Western blot. Bone marrow was isolated from TRIM59-cKO and TRIM59 flox/flox mice and induced to differentiate into bone marrow-derived macrophages (BMDMs). These BMDMs were stimulated with LPS and the supernatants of cell culture were collected at 3, 6, 12 and 24 h after stimulation to detect IL-10 level by ELISA. In addition, mouse models of cecal ligation and puncture (CLP) were established, and bronchoalveolar lavage fluid (BALF) samples were collected at the same time points to detect IL-10 level by ELISA. Histopathological changes in lung tissues were observed after HE staining. Results:There was a significant change in glucose metabolism-related genes in macrophages with high expression of TRIM59, and the content of lactic acid increased significantly. Compared with the control group, the expression of HIF-1α at mRNA level in BMDMs from TRIM59-cKO mice decreased after LPS stimulation ( P<0.05); the level of IL-10 increased at 3 h and 24 h in the TRIM59-cKO group, but there was no significant difference in IL-10 level at 6 h or 12 h between the two groups. In the TRIM59-cKO mouse model of CLP, the levels of IL-10 in the BALF samples increased with time, but decreased at 24 h. The level of IL-10 was higher in the TRIM59-cKO mouse model group than that in the control group at each time point ( P<0.05 or P<0.01). Conclusions:TRIM59 can inhibit inflammation and lung injury by decreasing HIF-1α-mediated lactate secretion and IL-10 expression in macrophages. This study provides a new idea for developing novel anti-sepsis drugs based on TRIM59.

Objective:To investigate the performance of medical students with different cognitive styles and temperament types in the flipped classroom of pediatrics.Methods:A total of 85 medical students of the class of 2018 in eight-year program who studied the course of Pediatrics 2 in West China Medical School, Sichuan University, were selected and received the flipped classroom teaching of pediatrics. The cognitive style figure test was used to investigate the cognitive style of students, and the temperament self-test questionnaire was used to investigate the temperament type of students. The methods such as the cluster analysis, the ANOVA analysis of variance, the Pearson correlation analysis, and the chi-square test were used to describe the distribution of flipped classroom scores and related differences between the students with different cognitive styles and temperament types.Results:There were four temperament types of these students, i.e., choleric and sanguine temperament, sanguine and phlegmatic temperament, melancholic temperament, and choleric temperament, accounting for 28.24%, 23.53%, 27.06%, and 21.18%, respectively. There were two cognitive styles of field independence and field dependence, accounting for 51.76% and 48.24%, respectively. There was a significant difference in flipped classroom scores between the students with different cognitive styles ( t=3.18, P<0.05), while there was no significant difference in such scores between the students with different temperament types ( F=0.38, P>0.05). The correlation analysis showed that the score of phlegmatic temperament was significantly negatively correlated with flipped classroom scores ( r=-0.283, P<0.05), and the score of cognitive test was significantly positively correlated with flipped classroom scores ( r=0.346, P<0.05). Conclusions:In the flipped classroom teaching of pediatrics, it is necessary to flexibly apply specific interaction and evaluation methods in students with different temperament types and cognitive styles and grasp the relationship between cooperative learning and independent learning. The design of different links of flipped classroom should be further improved.

Objective To discuss the cognition of interventional radiology(IR)and employment intention in the students majoring in imaging technology in medical school.Methods From June 7 to July 31 of 2023,a voluntary and anonymous online questionnaire survey concerning the cognition of IR and employment intention was conducted in the students majoring in medical imaging technology in Sichuan University,North Sichuan Medical College,Harbin Medical University,Hebei Medical University,Changzhi Medical College and Sichuan Vocational College of Health and Rehabilitation.The data obtained from the survey were analyzed by descriptive analysis and chi-square test using SPSS 24.0 statistical software.Results A total of 126 valid questionnaires were received.Eighty-seven students(69.05％),94 students(74.61％)and 81(64.28％)students had no knowledge or just had a little bit knowledge about the medical position and current status of IR in the fields of cardiovascular diseases,neurological diseases,and tumor diagnosis and treatment respectively.The IR course was obligatory course for the medical imaging technology specialty in all the schools participating in this survey,and 112 students(91.8％)stated that the school curriculum is the main way to acquire knowledge of IR,and the internet platforms,television science popularization and academic conferences were the other ways to acquire knowledge of IR.Four students(3.17％),17 students(13.49％),57 students(45.24％),39 students(30.95％)and 9 students(7.14％)participating in this survey expressed that they had no intention,no willingness,neutral attitude,high willingness and high intention respectively to engage in IR work in future.The difference in the degree of willingness to engage in IR specialty in future between students of different gender as well as between students with different schooling level was not statistically significant,and the exposure to radiation,work-related high stress,and long working time were the main influencing factors for students to consider IR as their professional career.Conclusion At present,both the cognition of IR and the employment intention are not high in the students majoring in imaging technology in medical school.Therefore,it is very important to improve their cognition of IR and willingness to engage in IR profession.

Objective To observe the value of ultrasound for diagnosing esophageal foreign body in children.Methods Ultrasonic manifestations of 45 children with esophageal foreign body were retrospectively analyzed,and the diagnostic value of ultrasound was evaluated.Results Among 45 cases,cervical esophageal foreign body was found in 40 cases(40/45,88.89%),while thoracic esophageal foreign body was detected in 5 cases(5/45,11.11%).Ultrasound correctly diagnosed 44 cases of esophageal foreign body,with an accuracy rate of 97.78%(44/45).Among different kinds of foreign bodies,fruit pits mainly presented as arc strong echogenicity accompanied by behind sound shadow,plastic stickers exhibited strong echogenicity with clear edges in the form of stripes,fish bones presented as irregular or slender strong echogenicity,button batteries demonstrated in arc/short strip strong echogenicity accompanied by sound shadows in the rear,while cooked albumen appeared as irregular chunks without echo,and the sarcocarp,toy parts and coins often presented as different shaped moderate/strong/mixed echogenicity,metallic foreign bodies with"comet tail"sign behind the strong echoes.Among 44 cases ultrasound correctly diagnosed esophageal foreign body,no abnormal changes of surrounding esophageal wall was found in 31 cases(31/44,70.45%),whereas mucosal necrosis injury and ulcer formation were detected in 7 cases(7/44,15.91%),inflammatory edema of esophageal wall were noticed in 3 cases(3/44,6.82%),and 3 cases(3/44,6.82%)were found with esophageal perforation.Conclusion Ultrasound was convenient and feasible for diagnosing esophageal foreign body in children with high accuracy.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

OBJECTIVES: The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage. METHODS: A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR. RESULTS: Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage. CONCLUSIONS The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.
Humans ; Diabetes Mellitus, Type 2/complications* ; Creatinine ; Vitamin D-Binding Protein/urine* ; Lipocalin-2/urine* ; Kidney/metabolism* ; Glomerular Filtration Rate ; Biomarkers

Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ . Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Brain Neoplasms/drug therapy* ; Carcinoma ; Tumor Microenvironment

OBJECTIVE: To investigate the preparation and properties of the novel silica (SiO ₂)/hydroxyapatite (HAP) whiskers porous ceramics scaffold. METHODS: The HAP whiskers were modified by the SiO ₂ microspheres using the Stöber method. Three types of SiO ₂/HAP whiskers were fabricated under different factors (for the No.1 samples, the content of tetraethoxysilane, stirring time, calcination temperature, and soaking time were 10 mL, 12 hours, 560℃, and 0.5 hours, respectively; and in the No.2 samples, those were 15 mL, 24 hours, 650℃, and 2 hours, respectively; while those in the No.3 samples were 20 mL, 48 hours, 750℃, and 4 hours, respectively). The phase and morphology of the self-made HAP whisker and 3 types of SiO ₂/HAP whiskers were detected by the X-ray diffraction analysis and scanning electron microscopy. Taken the self-made HAP whisker and 3 types of SiO ₂/HAP whiskers as raw materials, various porous ceramic materials were prepared using the mechanical foaming method combined with extrusion molding method, and the low-temperature heat treatment. The pore structure of porous ceramics was observed by scanning electron microscopy. Its porosity and pore size distribution were measured. And further the axial compressive strength was measured, and the biodegradability was detected by simulated body fluid. Cell counting kit 8 method was used to conduct cytotoxicity experiments on the extract of porous ceramics. RESULTS: The SiO ₂ microspheres modified HAP whiskers and its porous ceramic materials were prepared successfully, respectively. In the SiO ₂/HAP whiskers, the amorphous SiO ₂ microspheres with a diameter of 200 nm, uniform distribution and good adhesion were attached to the surface of the whiskers, and the number of microspheres was controllable. The apparent porosity of the porous ceramic scaffold was about 78%, and its pore structure was composed of neatly arranged longitudinal through-holes and a large number of micro/nano through-holes. Compared with HAP whisker porous ceramic, the axial compressive strength of the SiO ₂/HAP whisker porous ceramics could reach 1.0 MPa, which increased the strength by nearly 4 times. Among them, the axial compressive strength of the No.2 SiO ₂/HAP whisker porous ceramic was the highest. The SiO ₂ microspheres attached to the surface of the whiskers could provide sites for the deposition of apatite. With the content of SiO ₂ microspheres increased, the deposition rate of apatite accelerated. The cytotoxicity level of the prepared porous ceramics ranged from 0 to 1, without cytotoxicity. CONCLUSION SiO ₂/HAP whisker porous ceramics have good biological activity, high porosity, three-dimensional complex pore structure, good axial compressive strength, and no cytotoxicity, which make it a promising scaffold material for bone tissue engineering.
Animals ; Durapatite ; Porosity ; Vibrissae ; Apatites ; Ceramics ; Silicon Dioxide

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*