Objective:To explore the regulatory mechanism of voltage-dependent anion channel 1(VDAC1) on the proliferation, migration and invasion of lung adenocarcinoma(LUAD) cells.Methods:This study employed a combination of bioinformatics and experimental validation methods, conducting bioinformatics analysis and cytological experimental validation in the central laboratory of the School of Medicine, Anhui University of Science and Technology from February 2023 to August 2024.Clinical histological specimen validation was performed using immunohistochemistry, and a retrospective analysis was conducted on 5 cases of lung adenocarcinoma and adjacent samples from Huai′an First People′s Hospital affiliated with Nanjing Medical University. The TCGA network database was analyzed for the expression pattern, prognostic value, and functional enrichment of VDAC1 in LUAD. A549 cells with VDAC1 knockdown and H1650 cells with VDAC1 overexpression were established through lentiviral transfection. The expression difference of VDAC1 protein in LUAD and adjacent tissue specimens was detected by immunohistochemistry.The effects of VDAC1 on the proliferation, migration, and invasion capabilities were explored through CCK8 assay, scratch healing assay, and Transwell assay.The activation levels of epithelial-mesenchymal transition (EMT) marker proteins, cell cycle-dependent kinases, and molecules in the PI3K/AKT/mTOR signaling pathway were detected by Western blot.Results:Bioinformatics analysis revealed that VDAC1 was highly expressed in LUAD cells ( P<0.000 1) and was an independent risk factor for LUAD ( P<0.000 1). Functional enrichment analysis showed significant enrichment of the PI3K/AKT/mTOR, G2M checkpoint, and P53 signaling pathways ( P<0.001). Compared to adjacent control tissues, the expression level of VDAC1 protein is higher in lung adenocarcinoma tissues.Overexpression of VDAC1 promoted the proliferation ( P<0.000 1), migration, and invasion( P<0.01) of H1650 cells, while knockdown of VDAC1 inhibited the proliferation ( P<0.000 1), migration, and invasion ( P<0.05) of A549 cells.Western Blot experiments showed that compared to the control group, the expression levels of vimentin (1.10±0.11 vs 2.39±0.15, P<0.001), N-cadherin (0.94±0.12 vs 2.72±0.06, P<0.001), CDK1 (0.93±0.04 vs 1.53±0.03, P<0.000 1), CDK2 (1.04±0.13 vs 2.29±0.06, P<0.001), CDK4 (0.90±0.03 vs 2.00±0.11, P<0.01), p-PI3K (1.08±0.13 vs 1.85±0.12, P<0.01), and p-AKT (1.03±0.11 vs 1.69±0.06, P<0.001) were increased in H1650 cells overexpressing VDAC1, while E-cadherin expression decreased (2.18±0.14 vs 0.997±0.11, P<0.001).In contrast, in A549 cells with VDAC1 knockdown, the expression levels of vimentin (1.70±0.26 vs 0.97±0.09, P<0.05), N-cadherin (1.98±0.25 vs 1.03±0.06, P<0.05), CDK1 (1.13±0.03 vs 0.95±0.02, P<0.01), CDK2 (2.29±0.12 vs 0.92±0.10, P<0.001), CDK4 (1.71±0.096 vs 1.12±0.11, P<0.01), p-PI3K (1.67±0.09 vs 0.97±0.03, P<0.001), and p-AKT (1.53±0.04 vs 1.02±0.03, P<0.000 1) decreased, while E-cadherin expression increased (1.04±0.04 vs 1.85±0.26, P<0.05). Conclusions:VDAC1 may promote the proliferation, migration, and invasion of LUAD cells by activating EMT and cyclin-dependent kinases through the PI3K/AKT/mTOR pathway.

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

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To explore the regulatory mechanism of voltage-dependent anion channel 1(VDAC1) on the proliferation, migration and invasion of lung adenocarcinoma(LUAD) cells.Methods:This study employed a combination of bioinformatics and experimental validation methods, conducting bioinformatics analysis and cytological experimental validation in the central laboratory of the School of Medicine, Anhui University of Science and Technology from February 2023 to August 2024.Clinical histological specimen validation was performed using immunohistochemistry, and a retrospective analysis was conducted on 5 cases of lung adenocarcinoma and adjacent samples from Huai′an First People′s Hospital affiliated with Nanjing Medical University. The TCGA network database was analyzed for the expression pattern, prognostic value, and functional enrichment of VDAC1 in LUAD. A549 cells with VDAC1 knockdown and H1650 cells with VDAC1 overexpression were established through lentiviral transfection. The expression difference of VDAC1 protein in LUAD and adjacent tissue specimens was detected by immunohistochemistry.The effects of VDAC1 on the proliferation, migration, and invasion capabilities were explored through CCK8 assay, scratch healing assay, and Transwell assay.The activation levels of epithelial-mesenchymal transition (EMT) marker proteins, cell cycle-dependent kinases, and molecules in the PI3K/AKT/mTOR signaling pathway were detected by Western blot.Results:Bioinformatics analysis revealed that VDAC1 was highly expressed in LUAD cells ( P<0.000 1) and was an independent risk factor for LUAD ( P<0.000 1). Functional enrichment analysis showed significant enrichment of the PI3K/AKT/mTOR, G2M checkpoint, and P53 signaling pathways ( P<0.001). Compared to adjacent control tissues, the expression level of VDAC1 protein is higher in lung adenocarcinoma tissues.Overexpression of VDAC1 promoted the proliferation ( P<0.000 1), migration, and invasion( P<0.01) of H1650 cells, while knockdown of VDAC1 inhibited the proliferation ( P<0.000 1), migration, and invasion ( P<0.05) of A549 cells.Western Blot experiments showed that compared to the control group, the expression levels of vimentin (1.10±0.11 vs 2.39±0.15, P<0.001), N-cadherin (0.94±0.12 vs 2.72±0.06, P<0.001), CDK1 (0.93±0.04 vs 1.53±0.03, P<0.000 1), CDK2 (1.04±0.13 vs 2.29±0.06, P<0.001), CDK4 (0.90±0.03 vs 2.00±0.11, P<0.01), p-PI3K (1.08±0.13 vs 1.85±0.12, P<0.01), and p-AKT (1.03±0.11 vs 1.69±0.06, P<0.001) were increased in H1650 cells overexpressing VDAC1, while E-cadherin expression decreased (2.18±0.14 vs 0.997±0.11, P<0.001).In contrast, in A549 cells with VDAC1 knockdown, the expression levels of vimentin (1.70±0.26 vs 0.97±0.09, P<0.05), N-cadherin (1.98±0.25 vs 1.03±0.06, P<0.05), CDK1 (1.13±0.03 vs 0.95±0.02, P<0.01), CDK2 (2.29±0.12 vs 0.92±0.10, P<0.001), CDK4 (1.71±0.096 vs 1.12±0.11, P<0.01), p-PI3K (1.67±0.09 vs 0.97±0.03, P<0.001), and p-AKT (1.53±0.04 vs 1.02±0.03, P<0.000 1) decreased, while E-cadherin expression increased (1.04±0.04 vs 1.85±0.26, P<0.05). Conclusions:VDAC1 may promote the proliferation, migration, and invasion of LUAD cells by activating EMT and cyclin-dependent kinases through the PI3K/AKT/mTOR pathway.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

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 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.

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.