Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.

The glymphatic system is an important pathway for fluid drainage and metabolic waste clearance in the central nervous system. Its core mechanism involves the active cerebrospinal fluid-interstitial fluid circulation process mediated by perivascular spaces and aquaporin-4 channels located on astrocytic endfeet. This process is crucial for eliminating neurotoxic substances such as β-amyloid and tau proteins, as well as maintaining homeostasis in the central nervous system. Recent studies have shown that dynamic changes in the glymphatic system are associated with recovery after ischemic stroke. This article elaborates on the role of the glymphatic system in ischemic stroke and evaluates its potential value as a novel therapeutic target, providing new insights for post-stroke treatment strategies.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

Objective:To analyze the value of diffusion tensor imaging (DTI) combined with magnetic resonance spectroscopy (MRS) in the clinical grading and prognosis assessment of brain glioma.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with brain glioma admitted to Yan'an People's Hospital from January 2010 to December 2023. The cohort included 40 males and 32 females, with ages ranging from 25 to 76 years and an average age of (40.3 ± 6.8) years. All patients underwent routine magnetic resonance imaging plain scans, contrast-enhanced ultrasound examination, DTI, and MRS prior to surgery. Measurements were conducted for fractional anisotropy (FA), N-acetyl aspartate (NAA), choline compounds (Cho), and creatinine (Cr). Additionally, the ratios of NAA/Cho, Cho/Cr, and NAA/Cr were calculated. The imaging characteristics of brain glioma were analyzed, and the clinical utility of these indicators for grading and prognosis assessment of brain glioma was evaluated.Results:DTI results of the 72 included patients revealed disruption of the white matter fiber tracts surrounding the tumors. MRS of the 72 included patients showed either approximately normal values or indicated elevated Cho and Cr levels, along with decreased NAA levels. Diffuse mild to moderate enhancement was observed in 35 patients (48.61%), presenting with a patchy pattern that suggested a higher tumor grade. When comparing low-grade gliomas (LGG) and high-grade gliomas (HGG) to the corresponding healthy tissue, significant differences were observed in FA value in the peritumoral edema region [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.62 ± 0.08) × 10 -3 mm2/s for LGG, and (0.17 ± 0.05) × 10 -3 mm2/s vs. (0.62 ± 0.09) × 10 -3 mm2/s for HGG] , NAA/Cho ratio [(0.36 ± 0.11) vs. (1.41 ± 0.33) for LGG, and (0.19 ± 0.06) vs. (1.42 ± 0.35) for HGG], Cho/Cr ratio [(2.39 ± 0.51) vs. (1.12 ± 0.26) for LGG, and (3.81 ± 0.94) vs. (1.12 ± 0.28) for HGG], and NAA/Cr ratio [(0.75 ± 0.24) vs. (1.52 ± 0.31) for LGG, and (0.38 ± 0.12) vs. (1.52 ± 0.29) for HGG]. All observed differences were statistically significant ( tLGG = 26.56, 19.09, 14.03, 12.42; tHGG = 27.64, 21.90, 17.34, 22.97, all P < 0.05). There were statistically significant differences in FA [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.17 ± 0.05) × 10 -3 mm2/s], NAA/Cho [(0.36 ± 0.11) vs. (0.19 ± 0.06)], Cho/Cr [(2.39 ± 0.51) vs. (3.81 ± 0.94)], and NAA/Cr [(0.75 ± 0.24) vs. (0.38 ± 0.12)] between LGG and HGG ( t = 2.26, 7.85, 8.17, 7.95, all P < 0.05). Follow-up conducted 6 months to 3 years postoperatively revealed that the Cho/Cr ratio in the death group was significantly higher than that in the survival group [2.172 (1.662, 2.863) vs. 2.729 (2.431, 3.689), U = 2.17, P < 0.05]. However, there were no statistically significant differences in FA, NAA/Cho, and NAA/Cr values between survival and death groups ( P > 0.05). Conclusions:Combined DTI and MRS can reveal specific imaging characteristics of brain gliomas, providing valuable information for clinical grading of brain gliomas. Furthermore, the Cho/Cr ratio is associated with prognosis and may serve as a potential imaging biomarker for predicting the outcome of brain gliomas.

Objective To explore the expression of urinary exosomal microRNA-145-5p(miR-145-5p)and the targeted relationship with SLIT-ROBO guanosine triphosphatase activating protein 2(Srgap2)in diabetic kidney disease(DKD)mice.Methods A total of 11 db/db mice with random blood glucose≥16.7 mmol/L were selected to construct DKD model,and 10 C57BL/6J wild-type mice were assigned to the normal control(NC)group.The urine exosomes were isolated from each group.The expression of miR-145-5p in urinary exosomes and renal tissue were detected using RT-qPCR.Pearson correlation analysis was used to analyze the correlation between urinary exosomal miR-145-5p and UACR as well as the glycolipid metabolism indicators.Luciferase activity was performed to verify the targeting relationship between miR-145-5p and Srgap2.The expression Srgap2 and the ROCK activity in the renal tissues were detected using Western blot.Results Compared with NC group,the body weight,fasting plasma glucose(FPG),FIns,HbA1c,TC,UACR,urinary exosomal miR-145-5p and the expression of miR-145-5p in renal tissue and p-MYPT1 protein expression were significantly higher(P<0.05),while the expression of Srgap2 protein was significantly lower in DKD group(P<0.05).Pearson correlation analysis revealed that the exosomal miR-145-5p was positively correlated with UACR,FPG,HbA1c and TC(r=0.836,0.888,0.843,0.882,P<0.05).MiR-145-5p could directly target the Srgap2 protein and activate the ROCK pathway.Conclusions The expression of urinary exosomal miR-145-5p was significantly increased and the miR-145-5p/Srgap2/ROCK axis may be closely related to renal damage in DKD mice,and it is a promising diagnostic biomarker and future therapeutic target for DKD.

Objective To explore the expression of urinary exosomal microRNA-145-5p(miR-145-5p)and the targeted relationship with SLIT-ROBO guanosine triphosphatase activating protein 2(Srgap2)in diabetic kidney disease(DKD)mice.Methods A total of 11 db/db mice with random blood glucose≥16.7 mmol/L were selected to construct DKD model,and 10 C57BL/6J wild-type mice were assigned to the normal control(NC)group.The urine exosomes were isolated from each group.The expression of miR-145-5p in urinary exosomes and renal tissue were detected using RT-qPCR.Pearson correlation analysis was used to analyze the correlation between urinary exosomal miR-145-5p and UACR as well as the glycolipid metabolism indicators.Luciferase activity was performed to verify the targeting relationship between miR-145-5p and Srgap2.The expression Srgap2 and the ROCK activity in the renal tissues were detected using Western blot.Results Compared with NC group,the body weight,fasting plasma glucose(FPG),FIns,HbA1c,TC,UACR,urinary exosomal miR-145-5p and the expression of miR-145-5p in renal tissue and p-MYPT1 protein expression were significantly higher(P<0.05),while the expression of Srgap2 protein was significantly lower in DKD group(P<0.05).Pearson correlation analysis revealed that the exosomal miR-145-5p was positively correlated with UACR,FPG,HbA1c and TC(r=0.836,0.888,0.843,0.882,P<0.05).MiR-145-5p could directly target the Srgap2 protein and activate the ROCK pathway.Conclusions The expression of urinary exosomal miR-145-5p was significantly increased and the miR-145-5p/Srgap2/ROCK axis may be closely related to renal damage in DKD mice,and it is a promising diagnostic biomarker and future therapeutic target for DKD.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

Objective:To analyze the value of diffusion tensor imaging (DTI) combined with magnetic resonance spectroscopy (MRS) in the clinical grading and prognosis assessment of brain glioma.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with brain glioma admitted to Yan'an People's Hospital from January 2010 to December 2023. The cohort included 40 males and 32 females, with ages ranging from 25 to 76 years and an average age of (40.3 ± 6.8) years. All patients underwent routine magnetic resonance imaging plain scans, contrast-enhanced ultrasound examination, DTI, and MRS prior to surgery. Measurements were conducted for fractional anisotropy (FA), N-acetyl aspartate (NAA), choline compounds (Cho), and creatinine (Cr). Additionally, the ratios of NAA/Cho, Cho/Cr, and NAA/Cr were calculated. The imaging characteristics of brain glioma were analyzed, and the clinical utility of these indicators for grading and prognosis assessment of brain glioma was evaluated.Results:DTI results of the 72 included patients revealed disruption of the white matter fiber tracts surrounding the tumors. MRS of the 72 included patients showed either approximately normal values or indicated elevated Cho and Cr levels, along with decreased NAA levels. Diffuse mild to moderate enhancement was observed in 35 patients (48.61%), presenting with a patchy pattern that suggested a higher tumor grade. When comparing low-grade gliomas (LGG) and high-grade gliomas (HGG) to the corresponding healthy tissue, significant differences were observed in FA value in the peritumoral edema region [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.62 ± 0.08) × 10 -3 mm2/s for LGG, and (0.17 ± 0.05) × 10 -3 mm2/s vs. (0.62 ± 0.09) × 10 -3 mm2/s for HGG] , NAA/Cho ratio [(0.36 ± 0.11) vs. (1.41 ± 0.33) for LGG, and (0.19 ± 0.06) vs. (1.42 ± 0.35) for HGG], Cho/Cr ratio [(2.39 ± 0.51) vs. (1.12 ± 0.26) for LGG, and (3.81 ± 0.94) vs. (1.12 ± 0.28) for HGG], and NAA/Cr ratio [(0.75 ± 0.24) vs. (1.52 ± 0.31) for LGG, and (0.38 ± 0.12) vs. (1.52 ± 0.29) for HGG]. All observed differences were statistically significant ( tLGG = 26.56, 19.09, 14.03, 12.42; tHGG = 27.64, 21.90, 17.34, 22.97, all P < 0.05). There were statistically significant differences in FA [(0.20 ± 0.06) × 10 -3 mm2/s vs. (0.17 ± 0.05) × 10 -3 mm2/s], NAA/Cho [(0.36 ± 0.11) vs. (0.19 ± 0.06)], Cho/Cr [(2.39 ± 0.51) vs. (3.81 ± 0.94)], and NAA/Cr [(0.75 ± 0.24) vs. (0.38 ± 0.12)] between LGG and HGG ( t = 2.26, 7.85, 8.17, 7.95, all P < 0.05). Follow-up conducted 6 months to 3 years postoperatively revealed that the Cho/Cr ratio in the death group was significantly higher than that in the survival group [2.172 (1.662, 2.863) vs. 2.729 (2.431, 3.689), U = 2.17, P < 0.05]. However, there were no statistically significant differences in FA, NAA/Cho, and NAA/Cr values between survival and death groups ( P > 0.05). Conclusions:Combined DTI and MRS can reveal specific imaging characteristics of brain gliomas, providing valuable information for clinical grading of brain gliomas. Furthermore, the Cho/Cr ratio is associated with prognosis and may serve as a potential imaging biomarker for predicting the outcome of brain gliomas.

Objective:To identify characteristic genes of bipolar disorder using the random forest method and to construct a discriminative model for bipolar disorder using neural network approaches.Methods:The study utilized gene expression data from individuals with bipolar disorder ( n=20) and healthy controls ( n=15) from the GSE23848 dataset. Background correction was performed using negative control probes, and normalization was done with both negative and positive control probes. Differentially expressed genes were identified through linear model analysis and empirical Bayesian statistical methods. A random forest model was built for feature extraction of differentially expressed genes, and a neural network model was constructed using the characteristic genes identified by the random forest model. The discriminative efficiency of the model was validated on an independent external dataset GSE39653, which included bipolar disorder patients ( n=8) and healthy controls ( n=24). Biological functions of the characteristic genes were explored through gene ontology (GO) and protein-protein interaction networks (PPI). Results:A total of 1 330 differentially expressed genes related to bipolar disorder and 35 characteristic genes were selected for model construction. The final model was a feedforward neural network with four hidden layers and four dropout layers, possessing 50 433 trainable parameters. Bootstrap methods with 1 000 resampling were used to calculate the confidence intervals for sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and accuracy, all of which were 1. In the GSE39653 external validation set, the model′s AUC was 0.72. Enrichment analysis of the characteristic genes suggested that the functions of the genes in the model are related to mitochondrial structure and energy metabolism.Conclusion:The random forest method can identify characteristic genes of bipolar disorder, and a diagnostic model established through the combination of random forests and feedforward neural networks shows good classification performance in bipolar disorder.

Objective:To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.Methods:This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results:A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions:Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.