BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective:This study evaluates the horizontal sound localization ability of young and middle-aged individuals with symmetric sensorineural hearing loss (SNHL) in noisy environments. It also examines the impact of hearing loss severity and signal-to-noise ratio (SNR) on localization accuracy.Methods:In this cross-sectional study, conducted from April 2023 to April 2024, 135 young and middle-aged patients (73 males and 62 females, aged 18-60 years) with SNHL who sought care at Beijing Chaoyang Hospital, were categorized into mild, moderate, and moderate-to-severe hearing loss groups (45 per group), with 45 normal-hearing controls (23 males and 22 females, aged 20-60 years). Participants completed localization tasks in quiet and noisy environments with SNR levels of 5 dB, 0 dB, -5 dB, and-10 dB. Root mean square error (RMSE) was used to measure localization accuracy. Repeated measures ANOVA assessed the effects of hearing loss and SNR on RMSE, while, Pearson correlation evaluated the relationship between binaural 4-frequency pure-tone average (4fPTA) and RMSE. Multiple linear regression analyzed the predictive role of 4fPTA and age.Results:(1) Two-way repeated measures ANOVA showed that both hearing loss severity and SNR significantly affected RMSE ( F=92.67, P<0.01; F=430.29, P<0.01), with a significant interaction between the two factors( F=92.67, P<0.01). (2) RMSE increased with hearing loss severity. At SNRs of 5 dB, 0 dB, and-5 dB, the moderate-to-severe group had significantly higher RMSE than the mild and moderate groups ( P<0.01). No significant differences were found between mild and moderate groups ( P=0.53, 0.57, 0.22). At-10 dB SNR, significant differences were observed across all groups ( P<0.01). (3) RMSE increased non-linearly as SNR decreased. Mean RMSE values under quiet conditions and at SNRs of 5 dB, 0 dB, -5 dB, and-10 dB were (7.43±5.01)°, (9.80±5.74)°, (11.60±6.22)°, (14.56±7.07)°, and (18.74±8.02)°, respectively. (4) RMSE was significantly positively correlated with binaural 4fPTA ( r=0.54-0.58, P<0.01). Multiple linear regression analysis indicated that the binaural average 4fPTA significantly predicted RMSE ( P<0.01), explaining 30.5%-34.1% of RMSE variance. Age did not significantly contribute to RMSE variation. Conclusions:The degree of hearing loss and background noise SNR significantly affect horizontal sound localization in young and middle-aged SNHL patients. RMSE increases with hearing loss severity and decreases with higher SNR. The interaction between hearing loss and SNR is significant, and RMSE correlates with binaural 4fPTA. However, the regression model based on 4fPTA and age explains only part of the RMSE variance, suggesting other contributing factors.

Objective:To explore the clinical characteristics and therapeutic effect of perioral myoclonia with absences (PMA), in order to improve the clinicians′ understanding of the disease.Methods:The clinical manifestations during seizures, as well as interictal and ictal electroencephalogram (EEG) features of 3 PMA patients admitted to the Epilepsy Unit, Neurology Center, Beijing Tiantan Hospital, Capital Medical University from May to October 2024 were analyzed. The clinical manifestations, EEG characteristics, differential diagnosis, treatment experience of PMA patients were summarized by retrospective analysis combined with previous literature review.Results:The onset age of these 3 PMA cases was 15, 15, and 7 years, respectively. The prominent manifestation of seizure was perioral myoclonus without disturbance of consciousness. The duration of seizures was brief, less than 10 seconds. PMA can occur several times a day and was prone to present as continuous state of perioral myoclonus. Three patients had rare generalized tonic-clonic seizures (GTCS). The seizures could be controlled by sodium valproate, lamotrigine, levetiracetam, or combined treatment. Fifteen literatures about PMA were retrieved (4 in Chinese and 11 in English). A total of 31 patients (including these 3 patients) were included in the study, of whom 17 were males and 14 were females. The onset age was from 9 months to 34 [7.63 (2.19, 11.00)] years. Perioral myoclonus with varying degrees of disturbance of consciousness was the main seizure type, and 12 patients exhibited continuous state of perioral myoclonus, 24 patients had GTCS. Eight patients had a history of fever convulsion, 6 patients had mental or learning disabilities, and 11 patients had a family history of epilepsy or febrile convulsion. The ictal EEG showed around 3 Hz generalized spike-wave/multiple spike-wave discharges accompanied with synchronous myoelectric bursts. There were no specific abnormalities in physical examination of nervous system and cranial imaging in all the patients. Ten patients were initially diagnosed as focal epilepsy. Nine patients′ seizures were increased or worsened due to improper medication. Valproate, lamotrigine and levetiracetam were the main treatments of PMA, and the seizures of 21 patients were effectively controlled.Conclusions:PMA is clinically characterized by perioral myoclonia with varying degrees of disturbance of consciousness and is easy to be misdiagnosed as focal epilepsy, so it is necessary to use video EEG combined with synchronous electromyography to confirm the diagnosis. PMA should be treated with broad-spectrum antiseizure drugs.

OBJECTIVE To investigate the relationship between azimuth direction,angular intervals,and the accuracy of azimuthal sound source localization.METHODS Fifteen young subjects with normal hearing were tested using nine azimuth settings.The test results were presented as root mean square error and percentage confusion.RESULTS The confusion rate under high-frequency narrowband noise was significantly higher than that under broadband noise and three-syllable words.In the frontal direction,statistically significant differences were observed between the 20° and 10° intervals,as well as between the 20° and 15° intervals(P<0.05),but no significant difference was found between the 10° and 15° intervals(P>0.05).In the lateral and rear directions,statistically significant differences were found between the 30° and 15° intervals,as well as between the 30° and 20° intervals(P<0.05),but no significant difference was found between the 15° and 20° intervals(P>0.05).Statistically significant differences were observed between the frontal direction and both the lateral and rear directions(P<0.05),but no significant difference was found between the lateral and rear directions(P>0.05).CONCLUSION Using stimuli that contain broader bandwidth cues can more accurately reflect the subject's horizontal localization ability.For source azimuth identification tests using broadband noise and three-syllable words,it is recommended to use a 15° interval in the frontal direction,and a 20° interval in the lateral and rear directions.The frontal and lateral directions can be preferred for testing.

Objective By using intravoxel incoherent motion(IVIM)double exponential model liver multi-b value diffusion-weighted imaging(DWI)scanning technique to analyze the lesion's IVIM parameters before and after interventional treatment of hepatocellular carcinoma(HCC)with conventional transcatheter arterial chemoembolization(TACE)combined with CalliSpheres drug-loaded microspheres(DEB-TACE),based on which to quantitatively evaluate the efficacy of interventional therapy for HCC.Methods A total of 40 HCC patients,who were admitted to the Department of Interventional Therapy of Anqing Municipal Hospital of China from June 2022 to November 2023 to receive DEB-T ACE,were enrolled in this study.Routine MR examination,DWI and IVIM-DWI scan were performed before and at 1,3 and 6 months after treatment,and a total of 40 interest lesions were selected.The ADC value,perfusion fraction(f),pure diffusion coefficient(D),and perfusion-related diffusion coefficient(D*)of each lesion were analyzed.The receiver operating characteristic(ROC)curve was drawn to analyze the prognosis assessment value of IVIM-DWI parameters.Results After DEB-TACE treatment,the ADC value and D value were increased,and the f value was decreased when compared with their preoperative values,the differences were statistically significant(all P＜0.01).The ADC value and D value in the patients of effective group were remarkably higher than those in the patients of ineffective group,the differences were statistically significant(both P＜0.01);the f value in the patients of effective group was slightly lower than that in the patients of ineffective group,and the difference was statistically significant(P＜0.05).The areas under ROC curve of ADC value,D value and f value for evaluating efficacy were 0.762,0.877,and 0.708 respectively.The area under the curve for the joint assessment of the three parameters was 0.928,with the highest efficacy.Conclusion IVIM-DWI can quantitatively determine the microperfusion and activity of HCC lesions before and after interventional DEB-TACE treatment,and it can also evaluate the curative efficacy of interventional therapy for HCC as well as the outcome of HCC lesions.

Objective:This study evaluates the horizontal sound localization ability of young and middle-aged individuals with symmetric sensorineural hearing loss (SNHL) in noisy environments. It also examines the impact of hearing loss severity and signal-to-noise ratio (SNR) on localization accuracy.Methods:In this cross-sectional study, conducted from April 2023 to April 2024, 135 young and middle-aged patients (73 males and 62 females, aged 18-60 years) with SNHL who sought care at Beijing Chaoyang Hospital, were categorized into mild, moderate, and moderate-to-severe hearing loss groups (45 per group), with 45 normal-hearing controls (23 males and 22 females, aged 20-60 years). Participants completed localization tasks in quiet and noisy environments with SNR levels of 5 dB, 0 dB, -5 dB, and-10 dB. Root mean square error (RMSE) was used to measure localization accuracy. Repeated measures ANOVA assessed the effects of hearing loss and SNR on RMSE, while, Pearson correlation evaluated the relationship between binaural 4-frequency pure-tone average (4fPTA) and RMSE. Multiple linear regression analyzed the predictive role of 4fPTA and age.Results:(1) Two-way repeated measures ANOVA showed that both hearing loss severity and SNR significantly affected RMSE ( F=92.67, P<0.01; F=430.29, P<0.01), with a significant interaction between the two factors( F=92.67, P<0.01). (2) RMSE increased with hearing loss severity. At SNRs of 5 dB, 0 dB, and-5 dB, the moderate-to-severe group had significantly higher RMSE than the mild and moderate groups ( P<0.01). No significant differences were found between mild and moderate groups ( P=0.53, 0.57, 0.22). At-10 dB SNR, significant differences were observed across all groups ( P<0.01). (3) RMSE increased non-linearly as SNR decreased. Mean RMSE values under quiet conditions and at SNRs of 5 dB, 0 dB, -5 dB, and-10 dB were (7.43±5.01)°, (9.80±5.74)°, (11.60±6.22)°, (14.56±7.07)°, and (18.74±8.02)°, respectively. (4) RMSE was significantly positively correlated with binaural 4fPTA ( r=0.54-0.58, P<0.01). Multiple linear regression analysis indicated that the binaural average 4fPTA significantly predicted RMSE ( P<0.01), explaining 30.5%-34.1% of RMSE variance. Age did not significantly contribute to RMSE variation. Conclusions:The degree of hearing loss and background noise SNR significantly affect horizontal sound localization in young and middle-aged SNHL patients. RMSE increases with hearing loss severity and decreases with higher SNR. The interaction between hearing loss and SNR is significant, and RMSE correlates with binaural 4fPTA. However, the regression model based on 4fPTA and age explains only part of the RMSE variance, suggesting other contributing factors.

Objective:To explore the clinical characteristics and therapeutic effect of perioral myoclonia with absences (PMA), in order to improve the clinicians′ understanding of the disease.Methods:The clinical manifestations during seizures, as well as interictal and ictal electroencephalogram (EEG) features of 3 PMA patients admitted to the Epilepsy Unit, Neurology Center, Beijing Tiantan Hospital, Capital Medical University from May to October 2024 were analyzed. The clinical manifestations, EEG characteristics, differential diagnosis, treatment experience of PMA patients were summarized by retrospective analysis combined with previous literature review.Results:The onset age of these 3 PMA cases was 15, 15, and 7 years, respectively. The prominent manifestation of seizure was perioral myoclonus without disturbance of consciousness. The duration of seizures was brief, less than 10 seconds. PMA can occur several times a day and was prone to present as continuous state of perioral myoclonus. Three patients had rare generalized tonic-clonic seizures (GTCS). The seizures could be controlled by sodium valproate, lamotrigine, levetiracetam, or combined treatment. Fifteen literatures about PMA were retrieved (4 in Chinese and 11 in English). A total of 31 patients (including these 3 patients) were included in the study, of whom 17 were males and 14 were females. The onset age was from 9 months to 34 [7.63 (2.19, 11.00)] years. Perioral myoclonus with varying degrees of disturbance of consciousness was the main seizure type, and 12 patients exhibited continuous state of perioral myoclonus, 24 patients had GTCS. Eight patients had a history of fever convulsion, 6 patients had mental or learning disabilities, and 11 patients had a family history of epilepsy or febrile convulsion. The ictal EEG showed around 3 Hz generalized spike-wave/multiple spike-wave discharges accompanied with synchronous myoelectric bursts. There were no specific abnormalities in physical examination of nervous system and cranial imaging in all the patients. Ten patients were initially diagnosed as focal epilepsy. Nine patients′ seizures were increased or worsened due to improper medication. Valproate, lamotrigine and levetiracetam were the main treatments of PMA, and the seizures of 21 patients were effectively controlled.Conclusions:PMA is clinically characterized by perioral myoclonia with varying degrees of disturbance of consciousness and is easy to be misdiagnosed as focal epilepsy, so it is necessary to use video EEG combined with synchronous electromyography to confirm the diagnosis. PMA should be treated with broad-spectrum antiseizure drugs.

Objective:To explore the effect of ointment massage on the postoperative recovery of newborns who had intestinal tract operation, aim to construct an effective post-operative ointment and massage scheme and to enrich the content of enhanced recovery after surgery in the field of newborns.Methods:Delphi expert inquiry method was used to construct the ointment message scheme. A total of 64 newborns undergone intestinal surgery from May 2022 to May 2023 in Guangdong Women and Children Hospital were selected as study subjects and divided into routine group (34 cases) and ointment group (30 cases) by random number table method. In addition to routine treatment and nursing, the newborns in the ointment group also received ointment massage. The postoperative gastrointestinal drainage volume, fasting days, the first feeding time, hospital stay and the number of cases of vomiting and abdominal distension between the two groups were compared.Results:A total of 16 experts with (38.93 ± 5.13) years old were inquired, 6 males and 10 females. The effective questionnaire response rates for the two rounds of expert inquiry were 16/16 and 15/16, the expert authority coefficients were both≥0.80, the Kendall′s W coefficients were 0.117 and 0.107, with statistically significant differences (both P<0.05). A ointment message scheme consisting of 8 acupoints and 7 kinds of traditional Chinese medicines was determined. In the routine group, there were 19 males and 15 females with (268.47 ± 11.27) gestational age. In the ointment group, there were 20 males and 10 femles with (271.93 ± 10.36) gestational age. The postoperative gastrointestinal drainage volume, fasting days, the first feeding time and the hospital stay in the ointment group were 74.0 ml, 6.0 d, 158.5 h and 13.0 d, which had significant differences with the 184.5 ml, 7.5 d, 192.0 h, 16.5 d in the routine group ( Z values were 2.07-2.45, all P<0.05). The incidence of vomiting and abdominal distension in the ointment group were both 8 cases, which were lower than the 19 and 18 cases in the routine group with a statistically significant difference ( χ2 = 5.58, 4.56, both P<0.05). Conclusions:The ointment massage in this study has a positive impact on the recovery of newborn infants after intestinal surgery, with high safety, in line with enhanced recovery after surgery concept, and is worthy of promotion.

ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.