Objective Approximately 10% of patients with acute ischemic stroke （AIS） due to large vessel occlusion （LVO） present with mild stroke， and about 20% of the patients with mild stroke who do not receive reperfusion treatment will experience early neurological deterioration. This study aims to investigate the imaging indicators for predicting the onset of early neurologic deterioration （END） in patients with mild stroke due to LVO in the anterior circulation based on magnetic resonance imaging. Methods A total of 84 hospitalized patients who were diagnosed with acute anterior circulation infarction within 72 hours after disease onset in Henan Provincial People’s Hospital from January 1， 2021 to December 30， 2024 were enrolled，and 3.0 T magnetic resonance imaging was used to perform perfusion-weighted imaging （PWI） and diffusion-weighted imaging（DWI） for all patients with acute cerebral infarction. All patients had a baseline National Institutes of Health Stroke Scale（NIHSS） score of ≤5 within 24 hours after admission， and none of them received endovascular treatment. PWI and DWI imaging findings were collected from all patients to analyze regional cerebral blood flow （rCBF）， regional cerebral blood volume， mean transit time， and time to peak. The receiver operating characteristic curve was plotted to analyze the value of PWI parameters in predicting END in patients with mild stroke due to LVO in the anterior circulation who did not receive endovascular treatment. Continuous variables were stratified based on the optimal cut-off value of Youden index， and the multivariate logistic regression analysis was used to investigate the independent risk factors for END. Results The incidence rate of END was 31.0%， with the proportion of rCBF as the imaging indicator，cut-off value 29.3%. The proportion of rCBF was an independent risk factor for END （OR=14.41， 95%CI 7.00‒37.33）. Conclusion The proportion of rCBF≥29.3% has a certain value in predicting END in patients with mild stroke due to LVO in the anterior circulation and is an independent risk factor.

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

Objective:The aim of this study was to assess the frailty status of patients with heart failure undergoing CRT-D and then explore the predictive value of frailty for all-cause mortality and heart failure-related readmissions in these patients.Methods:We retrospectively included 374 patients with chronic heart failure who underwent CRT-D treatment at the First Affiliated Hospital of Xinjiang Medical University between June 2020 and June 2024. Based on the Tilburg Debilitation Assessment Scale, 175 patients (46.8%) were classified as frail while 199 (53.2%) were classified as non-frail. The baseline data between the two groups was compared using Cox regression analysis and Kaplan-Meier curves were used for survival analysis. P-values of <0.05 indicated statistically significant differences. Results:A total of 374 patients aged 25-93 (68±11) years were enrolled in this study, 101 (27.0%) of which were female. Among these, 175 (46.8%) were categorized as frail, and 199 (53.2%) were classified as non-frail. Over a median follow-up time of 23 (5, 45) months, 35 (9.4%) patients experienced all-cause mortality, with 30 (17.1%) deaths occurring in the frail group and 5 (2.5%) in the non-frail group; meanwhile, readmission events due to heart failure occurred in a total of 174 (46.5%) patients, including 122 (70.1%) in the frail group, and 52 (29.9%) in the non-frail group. Cox analysis showed that frailty was a significant determinant of all-cause mortality ( HR=21.25, 95% CI 3.99-113.30, P<0.001) and readmission among heart failure patients receiving CRT-D ( HR=2.52, 95% CI 1.73-3.68, P<0.001). Log-rank tests showed that the survival rate of patients in the frail group was significantly lower than that of patients in the non-frail group ( HR=7.22, 95% CI 2.80-18.60, P<0.001) and the risk of readmission events due to heart failure was significantly higher among patients in the frail group than among those in the non-frail group ( HR=2.75, 95% CI 1.98-3.81, P<0.001). Conclusions:Frailty is an independent predictor of postoperative all-cause mortality and the occurrence of heart failure-related readmissions in patients with heart failure treated receiving CRT-D.

Objective:To analyze the efficacy and safety of splenic artery occlusion combined with microwave ablation (MWA) in the treatment of hepatocellular carcinoma (HCC) complicated with liver cirrhosis and hypersplenism.Methods:Clinical data of 24 patients with HCC complicated with cirrhosis and secondary hypersplenism admitted to Airport Hospital of Tianjin Cancer Hospital from August 2023 to May 2024 were retrospectively analyzed, including 13 males and 11 females, aged (57.4±7.8) years. All patients were treated with splenic artery occlusion combined with MWA of spleen. Spleen volume measured by MRI before and after MWA, blood routine changes and postoperative complications (fever, bleeding, pain, renal failure and thrombosis) were analyzed.Results:The splenic volume of 24 patients measured by MRI before MWA was 692.4 (504.7, 1023.7) cm 3, and decreased to 225.0 (186.4, 285.6) cm 3 after treatment for 60 days ( Z=-3.23, P=0.001). The red blood cell counts were comparable before and after microwave ablation. The white blood cell count before MWA was 4.3 (3.2, 5.3)×10 9/L, which increased to 11.0 (8.6, 15.8)×10 9/L three days after treatment, and to 5.0 (3.3, 6.1)×10 9/L 90 days after treatment ( Z=-4.70, -0.34, P<0.001, P=0.732). The platelet count of the patients was 47.0 (39.0, 67.0)×10 9/L before MWA, which increased to 155.0 (120.3, 214.3)×10 9/L seven days after Treatment, and to 77.0 (63.0, 125.0)×10 9/L 90 days after treatment ( Z=-5.29, -2.51, P<0.001, P=0.012). None of the patients had obvious bleeding and no death occured. One patient (4.2%) developed renal failure, one patient (4.2%) had splenic venous thrombosis, 4 patients (16.7%) had pain of different degrees, and 5 patients (20.8%) had low fever. Conclusion:Splenic artery occlusion combined with MWA in the treatment of HCC complicated with liver cirrhosis and hypersplenism can significantly reduce spleen volume and increase platelet level with acceptable complications.

Bipolar disorder in children, a serious mental illness, often leads to significant functional impairment. Bipolar disorder onset in children is rare and is difficult to diagnose correctly due to the atypical clinical manifestations. Risperidone, as a second-generation antipsychotic, shows satisfied efficacy in children with bipolar disorder with dual effects on mood stabilization and psychotic symptom control. However, the long-term efficacy and safety of risperidone for the treatment of children with bipolar disorder remains unknown. This paper reports a 5-year-old child with bipolar disorder who was treated with low-dose risperidone and followed up for 4 years. The child showed significant emotional stabilization and behavioral improvement at the beginning of treatment. No serious side effects occurred during long-term follow-up. This paper detailly describes the clinical manifestations and diagnostic process of bipolar disorder onset in children in aspects of detailed clinical observation and evaluation. It summarizes the efficacy and safety of risperidone in the treatment of pediatric bipolar disorder to provide valuable experience for clinicians.

Major depressive disorder in adolescents is a serious psychiatric condition characterized by profound impairment in psychosocial functioning. Its primary symptoms include low mood, irritability, and anhedonia. Although pharmacological treatments and psychotherapy are currently recommended as first-line treatments, their effectiveness is limited, and pharmacological treatments may carry the risk of increased suicidal ideation. Therefore, exploring new, effective, and safe treatment options is an urgent priority. In recent years, intermittent theta burst stimulation (iTBS), a novel form of transcranial magnetic stimulation, has shown promising results in treating treatment-resistant depression in adults, drawing growing interest in its potential use in adolescents. iTBS modulates neural activity through magnetic stimulation of the cerebral cortex and has been shown to alleviate depressive symptoms, particularly when targeting the left dorsolateral prefrontal cortex (DLPFC). Given the high neuroplasticity of the adolescent brain during this critical developmental stage, adolescents may exhibit heightened sensitivity to iTBS, resulting in more enduring neuroregulatory effects. Research highlights the importance of precise targeting and individualized adjustment of stimulation intensity for optimal therapeutic outcomes. Additionally, accelerated iTBS (aiTBS) protocols have demonstrated faster clinical effects in treating acute or severe depression in adolescents, improving treatment adherence and partially mitigating suicidal tendencies. This review summarizes recent progress in the application of iTBS in adolescent depression, with a focus on its mechanisms, treatment parameters, and related research. The goal is to provide theoretical support and practical guidance for the clinical application of iTBS in adolescent depression care.

Objective To investigate the effects of periodontitis induced by Prevotella nigrescens(Pn)combined with ligation on cognitive functions in mice.Methods Twenty-four C57BL/6J mice were randomly divided into control group,ligation group,and ligation+Pn treatment(P+Pn)group.Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks.After modeling,alveolar bone resorption was assessed using micro-CT and histological analysis.Learning and memory abilities of the mice were evaluated using open field test(OFT),novel object recognition test(NORT),and Morris water maze test(MWM).Seven weeks after the start of modeling,the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.Results After 6 weeks of molar ligation,micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice,and histological analysis showed apical migration of the junctional epithelium,epithelial ridge hyperplasia,and lymphocyte infiltration,and these changes were obviously worsened in P+Pn group.Alveolar bone height decreased significantly in both ligation groups compared to the control group.Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT,showed reduced novel object preference in NORT,and exhibited longer escape latencies in MWM,and the mice in P+Pn group had significantly poorer performances in the tests.Histologically,obvious neuronal cytoplasmic degeneration,necrosis,nuclear pyknosis,vacuolation,and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.Conclusion Pn infection aggravates alveolar bone destruction,accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.

Objective:To investigate immunological non-responders (INRs) and immunological responders (IRs) during long-term antiretroviral therapy (ART), and study the dynamics of HIV reservoir and α4β7 cells in INRs and IRs and their correlation.Methods:Twenty-six patients with chronic HIV infection who received ART for 5 years were included. They were divided into INRs (CD4 + T cell counts≤350 cells/μl, n=9) and IRs (CD4 + T cell counts≥500 cells/μl, n=17) based on immune reconstitution outcomes. The percentages and numbers of α4β7 cells in both groups at baseline, ART 1, 3, and 5 years were detected by flow cytometry, and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods. HIV viral decay, α4β7 cells dynamics, and their correlations with T cells were compared at baseline, ART 1, 3 and 5 years between the two groups. Results:Over 5 years of ART, INRs exhibited higher HIV reservoir levels compared to IRs, but the decline trend was not slow. The counts of α4β7 cell were lower and the growth trend was slow in INRs ( P<0.05). α4β7 cell counts were strongly positively correlated with CD4 + T cell counts at all timepoints (Year 1: r=0.887; Year 3: r=0.878; Year 5: r=0.887; P all <0.001), while showing significantly negative correlations with activated CD38 + HLA-DR + CD4 + T cells (Year 1: r=-0.619, P=0.001), CD38 + HLA-DR + CD8 + T cells (Year 1: r=-0.517; Year 5: r=-0.532; P all <0.01), and PD-1 + CD4 + T cells (Year 1: r=-0.476, Year 5: r=-0.390, P all <0.05). Conclusions:During long-term ART, INRs maintained higher HIV reservoir and lower α4β7 cell counts compared with IRs, and decreased α4β7 cells may be associated with disease progression.

In recent years,protein and polypeptide drugs have developed rapidly and have been widely used to treat cancer,hepatitis,and other diseases.The activity of proteins and polypeptides is closely related to their structure.Protein structures can be divided into four levels:primary,secondary,tertiary,and quaternary structures.The primary structure determines the advanced structure and biological functions of proteins.To ensure drug safety,it is necessary to carry out structural characterization and quality control.The advanced structure is the basis for proteins to express their functions and activities,and changes in spatial structure can lead to alterations in functions.This article reviews the progress of research on the primary and advanced structure characterization of proteins and polypeptides,including techniques such as reversed-phase high-performance liquid chromatography,Edman degradation,mass spectrometry,and spectroscopy.It aims to provide a reference for the structural characterization and quality control of other protein and polypeptide drug products.