Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

Objective:To analyze the differences in paraspinal muscles between patients with degenerative lumbar spinal stenosis (DLSS) with or without spondylolisthesis and to assess the correlation between these differences and lumbar facet joint degeneration.Methods:The data of 68 patients with DLSS who underwent surgical treatment in our hospital from January 2021 to April 2023 was retrospectively analyzed. Of these, 22 were male (32.4%) and 46 were female (67.6%), with an average age of 69.7±5.9 years (range: 56-80 years). The DLSS group included 35 patients without spondylolisthesis [13 males (37.1%) and 22 females (62.9%)], average age 68.5±5.9 years (range: 56-80 years), while the DLSS+degenerative spondylolisthesis (DS) group included 33 patients with spondylolisthesis [9 males (27.3%) and 24 females (72.7%)], average age 70.9±5.7 years (range: 58-80 years). Magnetic resonance imaging (MRI) scans of the L 3-S 1 intervertebral disc levels were collected from all patients. Using ImageJ software, the cross-sectional area (CSA) and percentage of fat infiltration area (FIA%) of the erector spinae and multifidus muscles were measured. Additionally, the facet joint angle (FJA), facet overhang (FO), and facet effusion (FE) were evaluated using Surgimap software, and their correlation with CSA and FIA% of the paraspinal muscles was analyzed. Results:The FJA and FO in the DLSS+DS group (50.16°±11.08° and 7.67±2.25 mm) were significantly larger than those in the DLSS group (43.51°± 7.75° and 3.88±1.98 mm) ( P<0.05). However, differences in FE between the two groups were not statistically significant. The cross-sectional areas of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (576.66±112.70 mm 2,, 782.72±141.49 mm 2, and 817.88±185.22 mm 2,, respectively) were significantly smaller than those in the DLSS group (647.37±165.44 mm 2,, 881.20±202.10 mm 2,, and 995.06±211.25 mm 2,, respectively) ( P<0.05). The FIA% of the erector spinae at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (11.47%±5.14%, 14.84%±6.15%, 20.82%±7.41%) were significantly higher than those in the DLSS group (6.27%±2.83%, 10.81%±4.84%, 16.17%±5.88%) ( P<0.05). Similarly, the FIA% of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (18.04%±5.88%, 19.67%±5.78%, 19.31%±8.61%) were significantly higher than those in the DLSS group (9.85%±4.39%, 12.27%±3.70%, 14.65%±3.82%) ( P<0.05). No statistically significant differences were found in the CSA of the erector spinae at these levels between the two groups. The CSA of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in both groups were negatively correlated with FJA and FO ( r=-0.318, P=0.008; r=-0.381, P=0.001; r=-0.439, P<0.001; r=-0.290, P=0.016; r=-0.315, P=0.009; r=-0.479, P<0.001). The FIA% of the erector spinae at L 3, 4, L 4, 5, and the multifidus muscles at L 4, 5 and L 5S 1 were positively correlated with FJA ( r=0.352, P=0.003; r=0.344, P=0.004; r=0.300, P=0.013; r=0.359, P=0.003). Additionally, the FIA% of the erector spinae at L 3, 4, L 4, 5, and L 5S 1, and the multifidus muscles at L 3, 4 and L 4, 5 were positively correlated with FO ( r=0.409, P=0.001; r=0.248, P=0.042; r=0.277, P=0.022; r=0.500, P<0.001; r=0.447, P<0.001). There was no correlation between FE and CSA or FIA% of the erector spinae and multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in either group. Furthermore, FJA was positively correlated with FO ( r=0.369, P=0.002), but no correlation was observed between FE and FJA or FO. Conclusion:Compared to patients with lumbar spinal stenosis, those with degenerative lumbar spinal stenosis with spondylolisthesis exhibit more severe paraspinal muscle atrophy, a more sagittal orientation of the facet joints, and a higher degree of facet joint osteoarthritis. Patients with larger FJA and FO show more severe paraspinal muscle atrophy.

Objective:To observe the functional and esthetic results of endoscope-assisted septo-rhinoplasty via intranasal approach.Methods:The clinical data of 12 patients with septal deviation and nasal deformity in the University of Hong Kong-Shenzhen Hospital from June 2021 to June 2022 were analyzed, including 8 males and 4 females, aging 28 to 58 years. All patients were operated under general anesthesia. The septal deviation was corrected by hemitransfixion incision, combined with intercartilaginous incision and other intranasal or extranasal incisions to perform osteotomy, hump resection and saddle nose correction. Patient satisfaction with postoperative functional and aesthetic improvements was assessed through Nasal Obstruction Symptom Evaluation (NOSE), Rhinoplasty Outcome Evaluation (ROE), and Visual Analogue Scale (VAS).SPSS 25 software was used for statistical analysis.Results:The correction of nasal septum deviation was satisfactory in all 12 patients. Nasal obstruction was relieved, with NOSE score and VAS score of nasal ventilation decreased [(21.67±10.30) vs (70.83±14.12), (1.83±1.03) vs (8.33±0.89), t value was 9.49 and 16.30, respectively, both P<0.05]. The nasal appearance of 10 patients with crooked nose deformity was improved, with ROE score and VAS score of nasal appearance increased [(21.30±2.31) vs (8.10±3.31), (8.90±0.99) vs (3.80±1.62), t value was -11.85 and -9.33, respectively, both P<0.05];The nasal vestibule morphology of 2 patients with abnormal nasal vestibule was improved. During the follow-up of 12 to 24 months, no postoperative complication such as nasal septum perforation, nasal cavity adhesion or nasal dorsal collapse occurred in all patients. Conclusion:Endoscope-assisted septo-rhinoplasty via intranasal approach can resolve both functional and esthetic problems at the same time, improving outcomes while reducing surgical trauma.

By searching the literature on the application of entrustable professional activities in college education in China and globally, this article comprehensively analyzes the concept of entrustable professional activities, the development of evaluation items, the effectiveness of clinical application, the problems to be improved, and research prospects, so as to provide a useful reference for the reform and evaluation of competency-oriented medical education in China and the application of entrustable professional activities that can be repeated and promoted in clinical teaching.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the childhood Epstein-Barr virus(EBV)-positive lymphoproliferative diseases(EBV + LPD). Methods:The clinical features, treatment course, and prognosis of 9 children with EBV + LPD who underwent allo-HSCT in Children′s Hospital Affiliated to Zhengzhou University from July 2019 to July 2022 were analyzed retrospectively. Results:All the 9 children underwent histopathological examination, including 6 patients with EBV-positive T-cell lymphoproliferative disease (EBV + T-LPD), 1 with pulmonary lymphomatoid granuloma, and 2 with systemic EBV-positive T-cell lymphoma.There were 6 males and 3 females, with the median age of 5.8 (1.5-13.0) years.At the initial diagnosis, plasma and peripheral EBV-DNA copy at the initial diagnosis was (5.67-865.00)×10 2/mL, and (5.13-1 250.00)×10 2/mL, respectively.The EBV-DNA load of cerebrospinal fluid increased to (5.18-291.00)×10 2/mL in 3 cases.The whole exon sequencing data showed no abnormality in 3 cases, pulmonary lymphomatoid granuloma with the IL2RG mutation in 1 case and EBV + T-LPD with a hemizygous mutation in the SH2D1A gene as the pathogenic mutation in 1 case.Pathogenic mutations were not detected in the remaining 4 cases.The course of disease before transplantation was 5.4(3.0-10.0) months.Disease status before transplantation was as follows: all 3 cases of lymphomas had partial regression; 2 cases of EBV + T-LPD had active disease; and 4 cases had no active disease.Among the donors, there were 5 cases of half-matched relatives, 2 cases of full-matched siblings and 2 cases of unrelated full-matched donors.The median number of mononuclear cells in peripheral blood and/or bone marrow hematopoietic stem cell was 6.60(3.64-12.18)×10 8/kg, while the median implantation time of neutrophils was 18(9-23) days.One month after the transfusion of hematopoietic stem cells, plasma EBV-DNA copy was negative in all cases, and peripheral EBV-DNA copy was negative in 7 cases.The copy number in the other 2 cases was 10 2/mL.At the 3-month evaluation, plasma and peripheral EBV-DNA copy were negative in all cases.In addition, 3 cases of lymphomas achieved radiographic complete remission, and 6 cases of EBV + T-LPD were inactive.All transplant-related complications were effectively controlled after medication.Following the median follow-up of 24 (11-42) months, all patients had disease-free survival.Serious impact on the quality of life due to graft versus host disease was not reported. Conclusions:allo-HSCT is an effective treatment of childhood EBV + LPD, which is able to control transplant-related complications.Children with EBV + LPD can achieve long-term disease-free survival through transplantation.

Objective:To investigate urinary microalbumin to creatinine ratio (ACR) and α1-microglobulin to creatinine ratio (MCR) of people aged 40 years old and above in Shanxi province, and analyze the influencing factors of abnormal ACR and MCR, and to provide evidence for the prevention and control of chronic kidney diseases.Methods:It was a cross-sectional study. The data came from a screening study of chronic kidney diseases conducted by Shanxi Provincial People's Hospital from April to November 2019, involving aged 40 years old and above from 10 counties (Ningwu county, Yu county, Yangqu county, Lin county, Shouyang county, Zezhou county, Huozhou city, Hejin city, Linyi county and Ruicheng county) in Shanxi province. The related data were collected through questionnaire surveys, physical examinations, and blood and urine sample collection. Urinary α1-microglobulin, creatinine, and microalbuminuria were measured. Urinary ACR and MCR were calculated using urinary creatinine correction. ACR abnormality was defined as ≥30 mg/g, and MCR abnormality was defined as >23 mg/g. Covariate analysis was used to control confounding factors, and adjusted urinary ACR and MCR of 10 counties were calculated. Spearman correlation analysis and chi-square test were performed to analyze the factors associated with abnormal urinary ACR and MCR. Logistic regression analysis model was used to identify the influencing factors of abnormal urinary ACR and MCR.Results:A total of 12 285 residents were enrolled in the study, including 5 206 males (42.4%) and 7 079 females (57.6%). The median age was 58.0 (51.0, 66.0) years old. The median urinary ACR was 7.5 (4.5, 15.7) mg/g, and the median urinary MCR was 10.2 (6.4, 16.2) mg/g. A total of 1 572 individuals (12.80%) had urinary ACR abnormality and 1 450 individuals (11.80%) had urinary MCR abnormality. Yangqu county, Yuxian county, and Ningwu county had higher urinary ACR with (35.58±3.04) mg/g, (34.08±4.50) mg/g and (32.09±3.19) mg/g, respectively. The urinary MCR was generally similar among the 10 counties and Yangqu county had higher urinary MCR with (13.86±0.41) mg/g. In addition to Yu county, female individuals had higher urinary ACR compared to males in other counties, whereas female individuals had lower urinary MCR compared to males in 10 counties. Multivariate logistic regression analysis results showed that elevated triglyceride, fasting blood glucose, glycated hemoglobin, systolic blood pressure, diastolic blood pressure, age, body mass index and gender were independent influencing factors of abnormal urinary ACR and MCR (all P<0.05). Elevated blood homocysteine and low educational level were independent influencing factors of urinary MCR abnormality (both P<0.05). Conclusions:There are differences of gender and region in urinary ACR and MCR among individuals aged 40 years old and above in the 10 counties of Shanxi province. Triglyceride, fasting blood glucose, glycated hemoglobin, systolic blood pressure, diastolic blood pressure, age, gender, and body mass index are independent related factors of abnormal urinary ACR and MCR. Blood homocysteine and education level are independent related factors of abnormal urinary MCR.

Objective:To construct the evaluation index system of the core competence of neonatal specialist nurses, so as to provide reference for clinical training of neonatal specialist nurses.Methods:From January 2020, through literature review, theoretical analysis, interview, Delphi method and superiority chart, the evaluation index and weight of core competence of neonatal specialist nurses were determined.Results:Totally 28 experts in China were invited for 3 rounds of consultation. The effective recovery rate of the questionnaires was 93.33%(28/30) in the first round. The effective recovery rate of the questionnaires was 100.00%(28/28) in the second and third rounds. The authority coefficient of the experts was 0.85 in the third round. The Kendall′s coefficients of concordance of the first-level indexes, second-level indexes and third-level indexes were 0.150, 0.221 and 0.161, respectively. The final evaluation index system of the core competence of neonatal specialist nurses included 5 first-level indicators, 17 second-level indicators and 58 third-level indicators.Conclusions:The evaluation index system of the core competence of neonatal specialist nurses constructed in this study has certain scientific, reliable and clinical application value, which is conducive to the training of newborn specialized nurses in China.

Objective: A prognostic risk model for lung adenocarcinoma patients was established based on the cancer genome atlas(TCGA) database to explore the prognostic performance of autophagy related gene risk model for lung adenocarcinoma patients and its correlation with immune microenvironment． Methods: Clinical information and transcriptome data of lung adenocarcinoma patients were downloaded and extracted from TCGA database，and 232 autophagy-related genes were screened from the human autophagy database．cox regression analysis was used to screen out four autophagy genes independently associated with prognosis．The prognostic prediction model of lung adenocarcinoma was constructed by risk score ，and the performance of prediction model was evaluated by ROC curve．The relationship between risk scores and tumor immune microenvironment was explored using ESTIMATE ( estimation of stromal and immune cells in malignant tumour tissues using expression data) and CIBERSORT algo- rithms. Results: Thirty differentially expressed autophagy-related genes were identified in lung adenocarcinoma， of which four autophagy genes (BIRC5，ERO1A，ITGB4，NLRC4 ) could predict the prognosis of the patients. Grouped by risk score，the Kaplan-Meier analysis demonstrated that the survival rate of high-risk group was signifi- cantly lower than that of low-risk group(P＜0. 000 1) ．The ROC curve proved the accuracy of the model in predic- ting the prognosis of lung adenocarcinoma ( AUC = 0. 757 ) ．The ESTIMATE and CIBERSORT analyses revealed that the risk scoring model was associated with multiple immune cells and immune infiltrates in the tumor microenvi- ronment． Conclusion Compared with clinical data，the autophagy gene prognostic risk model can better predict the prognosis of patients with lung adenocarcinoma．In the high-risk group，CD4 + memory quiescent cells can im- prove prognosis in lung adenocarcinoma patients.

Objective : To explore the potential targets, pathways and related mechanisms of artesunate(ART) in the treatment of hepatocellular carcinoma(HCC) based on network pharmacology and Bioinformatics. Methods: The potential targets of ART were screened through pharmmapper database, PPI network was constructed and visual analysis was performed.The data of 424 HCC samples were downloaded from TCGA database, the data information of potential target genes were screened, and the differentially expressed target genes were analyzed.The key target genes were screened by univariate-multivariate COX regression analysis.Molecular docking software was used to conduct molecular docking between ART and key target genes.Differential expression and survival analysis of key target genes were performed using network database GEPIA2. KEGG pathway enrichment analysis was performed by R language. The effects of ART on the proliferation and migration of HCC cells were verified by MTS assay and scratch test. The expression of FABP5 in HCC cells was verified by qPCR and Western blot. Western blot was used to verify the protein changes of PI3K/AKT pathway. Results : A total of 282 potential target genes were screened by network pharmacology. Finally,three key target genes were screened out. The survival analysis of FABP5 in HCC was statistically significant(P<0. 01). Molecular docking showed that ART and FABP5 had the highest binding energy. Pathway enrichment analysis showed that FABP5 was mainly enriched in PI3K/AKT signaling pathway. Cell experiments verified that ART could inhibit the expression level of FABP5,that ART could regulate the PI3K/AKT pathway,and that ART could inhibit the proliferation and migration of HCC cells. Conclusion FABP5 may regulate the PI3K/AKT pathway by inhibiting FABP5 and thus affect HCC cell proliferation and migration,and FABP5may serve as a new target gene for ART therapy of HCC.