OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans ; Uterine Cervical Neoplasms/pathology* ; Oncolytic Viruses/genetics* ; Female ; HEK293 Cells ; Oncolytic Virotherapy/methods* ; Adenoviridae/genetics* ; Gene Editing/methods* ; Telomerase/genetics* ; Adenovirus E1A Proteins/genetics* ; Genetic Vectors/genetics* ; HeLa Cells

OBJECTIVE: Evaluate the clinical application effect of low-field infant MRI. METHODS: Using literature review, expert consultation, and two rounds of Delphi to determine the evaluation index system. Then retrospectively analyze and compare the data of low-field infant MRI and high-field MRI from January 2023 to December 2024. RESULTS: There is a certain gap between low-field infant MRI and high-field MRI in terms of signal-to-noise ratio, image uniformity, software system reliability, scanning time, user interface friendliness and image result consistency. However, there was no difference in terms of spatial resolution and image quality. The noise, hardware system reliability, mean time between failure and the rate of examination completed without sedation are better than that of high-field MRI. CONCLUSION Low-field infant MRI meets needs of clinical diagnostic and has stable performance. It can be used as a routine screening tool for brain diseases near the bed.
Magnetic Resonance Imaging/methods* ; Humans ; Infant ; Retrospective Studies ; Signal-To-Noise Ratio ; Reproducibility of Results ; Brain Diseases/diagnostic imaging* ; Brain/diagnostic imaging* ; Software

Objective:To evaluate the prognosis of Hall technique and traditional performed metal crown (PMC) restoration technique, and to follow up the occlusal changes before and after treatment with Hall technique, providing references for the promotion of Hall technique.Methods:Children who visited the Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University from May 2021 to December 2022 were screened according to the inclusion and exclusion criteria. The therapeutic effects of the two groups were followed up at three time points: 1, 2 and 3 months after operation. The observation results were divided into three outcomes: success (crown in place, no symptoms of pulpitis or periapical periodontitis, no obvious abnormality in occlusion, no need for further treatment), partial failure (crown falling off or crown broken, tooth defect can be repaired, reversible pulpitis) and complete failure (irreversible pulpitis or periapical periodontitis, crown falling off and tooth defect irreparable), and statistical analysis was made. At the same time, the Hall technique group was followed up at five time points as before operation, immediately after operation, 2 weeks after operation, 4 weeks after operation and 8 weeks after operation respectively, in which the occlusion was analyzed by Dental Prescale Ⅱ system. The vertical dimension of occlusion (VDO), overbite and coverage, and canine relationship were recorded and compared. Three-dimensional finite element method was used to model and analyze the stress of the teeth treated with traditional PMC treatment and Hall technique, and the differences between them were compared.Results:Finally, 21 children were included in the Hall technique group, including 12 boys and 9 girls, with age of (5.0±1.4) years. Meanwhile, 22 children including 15 boys and 7 girls were in the traditional PMC group, with age of (5.1±1.3) years. There were 0 cases of complete failure and 0 cases of partial failure both in the Hall technique group and in the traditional PMC group within 1 month. There were 0 cases of complete failure and 1 case of partial failure in the Hall technique group, while 0 cases of complete failure and 0 cases of partial failure in the traditional PMC group within 2 months after operation. Hall technique group failed completely in 1 case and partially in 1 case, while the traditional pre-crown group failed completely in 0 cases and partially in 0 cases 3 months after operation. There was no significant difference in the incidence of primary index/complete failure and secondary index/partial failure between Hall technique group and traditional PMC group (all P>0.05). The occlusal area and occlusal force of children treated with Hall technique decreased immediately after operation compared with those before operation, but gradually recovered to the preoperative level at 2, 4 and 8 weeks after operation. To elaborate, the occlusal area decreased significantly from (14.79±3.55) mm 2 before operation to (10.15±3.17) mm 2 immediately after operation ( P=0.001), and recovered to (15.58±3.39) mm 2 at 8 weeks after operation ( P>0.05 compared with pre-operation). The occlusal force decreased significantly from (436.94±109.59) N before operation to (292.70±96.05) N immediately after operation ( P=0.001), and recovered to (441.86±104.31) N at 8 weeks after operation ( P>0.05 compared with pre-operation). Overbite decreased significantly from (2.54±1.05) mm before operation to (1.80±0.94) mm immediately after operation ( P=0.044) and then recovered to (2.35±1.02) mm ( P>0.05 compared with pre-operation). The coverage changed from (2.41±0.66) mm before operation to (2.27±0.61) mm immediately after operation ( P>0.05) and then recovered to (2.48±0.62) mm ( P>0.05 compared with pre-operation). The canine relationship was (3.12±0.54) mm before operation, and decreased significantly immediately after operation (2.17±0.89) mm ( P=0.001), and recovered to (3.05±0.61) mm after 8 weeks ( P>0.05 compared with pre-operation). In the three-dimensional finite element analysis, the maximum stress of all parts of the affected tooth increased immediately after Hall technique treatment, but with occlusal adjustment, the maximum stress of all parts of the affected tooth decreased, which was similar to that of the traditional metal pre-crown group. The vertical load and oblique load of pre-crown decreased from 180.11 and 496.16 MPa to 108.05 and 297.69 MPa, respectively. The vertical load and oblique load of enamel decreased from 94.83 and 255.94 MPa to 57.21 and 156.44 MPa, respectively. The vertical load and oblique load of dentin decreased from 55.19 and 124.77 MPa to 33.19 and 74.59 MPa, respectively. Conclusions:During the experimental observation period, there is no obvious difference between Hall technique and traditional PMC treatment technology in terms of post-treatment occlusion and clinical prognosis, which supports clinical application.

Objective:To analyze the effectiveness of different localization methods in colostomy localization among rectal cancer patients with colostomy.Methods:A total of 158 rectal cancer patients who underwent laparoscopic Dixon operation combined with temporary ileostomy from January 2020 to December 2022 at the Peking University Third Hospital were retrospectively selected for the study. Patients were divided into a traditional localization group ( n=86) and a modified localization group ( n=72) based on preoperative colostomy localization methods. The preoperative colostomy localization adoption rate and the incidence of peristoma fecal dermatitis were compared between the two groups. Results:The preoperative colostomy localization adoption rate in modified localization group was higher than that in traditional localization group, and the incidence of peristoma fecal dermatitis was lower than that in traditional localization group, with statistically significant differences ( P<0.05) . Conclusions:The modified rectangular area localization method is accurate for colostomy localization and reduces the risk of colostomy complications in postoperative patients.

Objective:To evaluate the prognosis of Hall technique and traditional performed metal crown (PMC) restoration technique, and to follow up the occlusal changes before and after treatment with Hall technique, providing references for the promotion of Hall technique.Methods:Children who visited the Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University from May 2021 to December 2022 were screened according to the inclusion and exclusion criteria. The therapeutic effects of the two groups were followed up at three time points: 1, 2 and 3 months after operation. The observation results were divided into three outcomes: success (crown in place, no symptoms of pulpitis or periapical periodontitis, no obvious abnormality in occlusion, no need for further treatment), partial failure (crown falling off or crown broken, tooth defect can be repaired, reversible pulpitis) and complete failure (irreversible pulpitis or periapical periodontitis, crown falling off and tooth defect irreparable), and statistical analysis was made. At the same time, the Hall technique group was followed up at five time points as before operation, immediately after operation, 2 weeks after operation, 4 weeks after operation and 8 weeks after operation respectively, in which the occlusion was analyzed by Dental Prescale Ⅱ system. The vertical dimension of occlusion (VDO), overbite and coverage, and canine relationship were recorded and compared. Three-dimensional finite element method was used to model and analyze the stress of the teeth treated with traditional PMC treatment and Hall technique, and the differences between them were compared.Results:Finally, 21 children were included in the Hall technique group, including 12 boys and 9 girls, with age of (5.0±1.4) years. Meanwhile, 22 children including 15 boys and 7 girls were in the traditional PMC group, with age of (5.1±1.3) years. There were 0 cases of complete failure and 0 cases of partial failure both in the Hall technique group and in the traditional PMC group within 1 month. There were 0 cases of complete failure and 1 case of partial failure in the Hall technique group, while 0 cases of complete failure and 0 cases of partial failure in the traditional PMC group within 2 months after operation. Hall technique group failed completely in 1 case and partially in 1 case, while the traditional pre-crown group failed completely in 0 cases and partially in 0 cases 3 months after operation. There was no significant difference in the incidence of primary index/complete failure and secondary index/partial failure between Hall technique group and traditional PMC group (all P>0.05). The occlusal area and occlusal force of children treated with Hall technique decreased immediately after operation compared with those before operation, but gradually recovered to the preoperative level at 2, 4 and 8 weeks after operation. To elaborate, the occlusal area decreased significantly from (14.79±3.55) mm 2 before operation to (10.15±3.17) mm 2 immediately after operation ( P=0.001), and recovered to (15.58±3.39) mm 2 at 8 weeks after operation ( P>0.05 compared with pre-operation). The occlusal force decreased significantly from (436.94±109.59) N before operation to (292.70±96.05) N immediately after operation ( P=0.001), and recovered to (441.86±104.31) N at 8 weeks after operation ( P>0.05 compared with pre-operation). Overbite decreased significantly from (2.54±1.05) mm before operation to (1.80±0.94) mm immediately after operation ( P=0.044) and then recovered to (2.35±1.02) mm ( P>0.05 compared with pre-operation). The coverage changed from (2.41±0.66) mm before operation to (2.27±0.61) mm immediately after operation ( P>0.05) and then recovered to (2.48±0.62) mm ( P>0.05 compared with pre-operation). The canine relationship was (3.12±0.54) mm before operation, and decreased significantly immediately after operation (2.17±0.89) mm ( P=0.001), and recovered to (3.05±0.61) mm after 8 weeks ( P>0.05 compared with pre-operation). In the three-dimensional finite element analysis, the maximum stress of all parts of the affected tooth increased immediately after Hall technique treatment, but with occlusal adjustment, the maximum stress of all parts of the affected tooth decreased, which was similar to that of the traditional metal pre-crown group. The vertical load and oblique load of pre-crown decreased from 180.11 and 496.16 MPa to 108.05 and 297.69 MPa, respectively. The vertical load and oblique load of enamel decreased from 94.83 and 255.94 MPa to 57.21 and 156.44 MPa, respectively. The vertical load and oblique load of dentin decreased from 55.19 and 124.77 MPa to 33.19 and 74.59 MPa, respectively. Conclusions:During the experimental observation period, there is no obvious difference between Hall technique and traditional PMC treatment technology in terms of post-treatment occlusion and clinical prognosis, which supports clinical application.

Objective:To analyze the effectiveness of different localization methods in colostomy localization among rectal cancer patients with colostomy.Methods:A total of 158 rectal cancer patients who underwent laparoscopic Dixon operation combined with temporary ileostomy from January 2020 to December 2022 at the Peking University Third Hospital were retrospectively selected for the study. Patients were divided into a traditional localization group ( n=86) and a modified localization group ( n=72) based on preoperative colostomy localization methods. The preoperative colostomy localization adoption rate and the incidence of peristoma fecal dermatitis were compared between the two groups. Results:The preoperative colostomy localization adoption rate in modified localization group was higher than that in traditional localization group, and the incidence of peristoma fecal dermatitis was lower than that in traditional localization group, with statistically significant differences ( P<0.05) . Conclusions:The modified rectangular area localization method is accurate for colostomy localization and reduces the risk of colostomy complications in postoperative patients.

Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma (ESCC) progression, but how this splicing process is abnormally regulated remains elusive. Here, we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC. The long-form BOLA3 (BOLA3-L) containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis. Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells. Additionally, HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L. High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis. HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells, which were significantly rescued by BOLA3-L overexpression. Moreover, BOLA3-L played a significant role in mitochondrial structural and functional stability. E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3. Our findings provided novel insights into how alternative splicing contributes to ESCC progression.
Female ; Humans ; Male ; Mice ; Alternative Splicing ; Cell Line, Tumor ; Disease Progression ; Esophageal Neoplasms/pathology* ; Esophageal Squamous Cell Carcinoma/pathology* ; Exons/genetics* ; Gene Expression Regulation, Neoplastic ; Heterogeneous-Nuclear Ribonucleoprotein Group C/metabolism* ; Prognosis ; RNA, Long Noncoding/metabolism* ; Animals

Purpose To investigate the diagnostic value of 18F-FDOPA PET/CT imaging and semi-quantitative analysis platform for the diagnosis of Parkinson's disease(PD).Materials and Methods There were 27 healthy controls and 56 clinically diagnosed PD patients,including 33 early PD(Hoehn-Yahr class Ⅰ-Ⅱ)and 23 advanced PD(Hoehn-Yahr class Ⅲ-Ⅳ),underwent 18F-FDOPA PET imaging in Nanjing First Hospital,Nanjing Medical University were consecutively enrolled from January 2018 to December 2019.The striatal to occipital ratio(SORs)in radioactivity was calculated by HERMES BRASS platform,thereby completing the semi-quantitative analysis of the brain based on regions of interest and observing the asymmetry of the striatal subregions in early-stage PD and late-stage PD patients.Using artificial intelligence techniques to perform principal component analysis on the SORs of the striatal subregions in PD group and healthy control group,the degree of data aggregation and the distinguishability between groups were observed.Results The SORs was significantly reduced in the whole caudate,anterior,posterior putamen and striatum of advanced PD patients(t=9.02-11.72,P<0.000 1).The area under the curve was 0.952,0.973,0.995 and 0.982,respectively.Compared with the healthy control group,the loss of striatal asymmetry index(mean)in each subregion of the striatum in early PD group was caudate(7.61±5.50)%,anterior putamen(11.43±8.97)%,posterior putamen(17.17±11.63)%,and whole striatum(10.65±7.46)%,respectively.The uptake of 18F-FDOPA in the striatum of PD patients was significantly reduced,and the most obvious loss of early PD patients was contralateral posterior putamen,with a decrease of 34%.Conclusion The platform semi-quantitative analysis of 18F-FDOPA PET/CT images provides objective semi-quantitative values for early diagnosis and differential diagnosis of PD.Asymmetry in the striatum,especially in the putamen,may be an important parameter for early diagnosis of PD..

Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.