Objective To explore the differences in heartbeat-evoked response (HER) under drug-related cues and neutral cues in individuals with heroin use disorder (HUD), and analyze the correlation between HER potentials and immediate cue-induced craving scores. Methods Fifty HUD participants were recruited from the Chang’an Compulsory Isolation Drug Rehabilitation Center in Shaanxi Province from June to September 2024. Simultaneous acquisition of 64-channel electroencephalography (EEG) and electrocardiogram signals was performed. Twenty alternating segments of drug-related and neutral cue videos were presented, and participants rated their subjective craving after each segment using visual analogue scale (VAS) scores. Scalp EEG data were source analyzed to obtain cortical EEG signals and corresponding HER. Short-time Fourier transform was used to calculate the power spectral density (PSD) of EEG within a time window from 100 ms before the R-peak to 500 ms after it, using the R-peak as the time zero point. Cluster-based permutation testing was used to analyze PSD differences between drug-related and neutral cues in the HUD individuals. Pearson correlation analysis was performed to evaluate the correlation between HER potentials and VAS scores. Results In the 350–420 ms time window, HER potentials in the left posterior parietal, temporal, and posterior cingulate cortices were significantly lower under drug-related cues compared to neutral cues (P＜0.01); in the 140–210 ms time window, HER potentials in the right prefrontal cortex were significantly higher under drug-related cues compared to neutral cues (P＜0.01). Correlation analysis showed that HER potentials in the left temporal and left posterior cingulate cortices were significantly negatively correlated with VAS scores (P＜0.05). Drug-related cues enhanced PSD of γ power (30–100 Hz) in salience network (fronto-insular), parietal and occipital regions (P＜0.05). PSD integrations of low-γ power (40–60 Hz) in parietal region (350–400 ms) and high-γ power (70–100 Hz) in left salience network (fronto-parietal) and occipital regions (300–350 ms) were positively correlated with VAS scores (P＜0.05). Conclusions Drug-related cues may modulate cortical activity related to heartbeat perception in HUD individuals, and such dynamic changes in both time and frequency domains are stably associated with subjective craving.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

OBJECTIVE:Neuromuscular exercise is a new comprehensive rehabilitation therapy in recent years,but its effect on knee osteoarthritis is still controversial.The purpose of this paper is to systematically evaluate the efficacy of neuromuscular exercise on knee osteoarthritis pain and function. METHODS:The randomized controlled trials addressing neuromuscular exercise in the treatment of knee osteoarthritis pain and function were retrieved from PubMed,Cochrane Library,Embase,EBSCO,CNKI,Web of Science,China Biomedical Database(CBM),VIP,and WanFang Database.The retrieval time ranged from database inception to October 2023.The neuromuscular training group(experimental group)was given neuromuscular training or neuromuscular training as the main intervention;the control group was a blank group or given conventional rehabilitation.Outcome indicators included the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,walking time,knee stability,and the maximum number of knee flexion in 30 seconds.The risk of bias was evaluated by the Cochrane Collaboration tool and the Physiotherapy Evidence Database.Meta-analysis was performed using RevMan 5.4 software. RESULTS:A total of 11 randomized controlled trials were included,and 628 samples were extracted.The results of Meta-analysis showed that the experimental group was superior to the control group in terms of WOMAC pain score[standardized mean difference(SMD)=0.38,95%confidence interval(CI):0.08-0.69,P=0.01],knee stability(SMD=0.57,95%CI:0.23-0.92,P=0.001),the maximum number of knee joint flexion in 30 seconds(SMD=0.35,95%CI:0.05-0.65,P=0.02),and WOMAC physical function score(SMD=-0.79,95%CI:-1.30 to-0.28,P=0.002).In both groups,walking speed was increased and walking ability was improved in patients with knee osteoarthritis,but there was no significant difference(walking time:SMD=-0.22,95%CI:-0.48-0.03,P=0.09). CONCLUSION:Neuromuscular exercise can effectively improve knee joint pain,enhance the stability of the knee joint,and promote functional recovery in patients with knee osteoarthritis.However,more high-quality randomized controlled trials are still needed to further confirm the research.

Objective To investigate the imaging features of Langerhans cell histiocytosis(LCH)in the long bones of the limbs in children.Methods The clinical and imaging data of 23 children with long bones of the limbs were analyzed retrospectively.X-ray examinations were performed in 21 cases,CT scans in 16 cases,and MRI scans in 19 cases.Results The lesions were located in femur in 14 cases,tibia in 3 cases,fibula in 2 cases,humerus in 1 case,ulna in 2 cases,and both tibia and fibula in 1 case.Lesions were found in the diaphysis in 16 cases and the metaphysis in 7 cases(involving the epiphysis in 2 cases).Bone destruction appeared as oval,irregular,or eccentric shapes,with clear boundaries in 17 cases,blurred boundaries in 6 cases,and sclerosis in 6 cases.The average CT value was(48.27±8.20)HU,with"gear-like"changes in the axial view in 10 cases."Sleeve-like"periosteal reaction was observed in 14 cases,localized periosteal reaction in 5 cases,and no periosteal reaction in 4 cases.The lesions showed iso-or slightly hypointense signals on T1 WI,hyperintense signals on T2 WI,and hyperintense signals on diffusion weighted imaging(DWI),with an average apparent diffusion coefficient(ADC)value of(1.26±0.17)×10-3 mm2/s.Soft tissue masses were found in 7 cases.After enhancement,moderate to marked enhancement was observed in 9 cases,with lace-like enhancement in 6 cases.Among the 17 cases followed up,13 cases returned to normal or had only residual bone cortical thickening,3 cases showed a reduction in lesion size,and 1 case died.Conclusion The imaging features of LCH in the long bones in children have certain characteristics,but can still be easily confused with infections or malignant bone tumors.A comprehensive analysis combining clinical and imaging features is necessary to improve diagnostic accuracy.