Rheumatic diseases are a group of chronic disorders characterized by abnormalities in the immune system， while portal hypertension occurs due to increased blood flow or heightened resistance in the portal venous system or obstruction of hepatic venous outflow. Both rheumatic diseases and their medications can lead to noncirrhotic portal hypertension. The hypercoagulable state associated with rheumatic diseases can result in thrombosis within the portal and hepatic venous systems， and damage to the intrahepatic portal system and hepatic sinusoidal endothelial system can lead to porto-sinusoidal vascular disease and hepatic sinusoidal obstruction syndrome. Moreover， drugs used for the treatment of rheumatic diseases may cause liver parenchymal injury， which further leads to liver fibrosis and cirrhosis， or they may damage the hepatic vascular endothelium and thus cause noncirrhotic portal hypertension. This article elaborates on the mechanisms and characteristics by which common rheumatic diseases and their therapeutic agents lead to portal hypertension， in order to provide insights and assistance for clinical diagnosis， treatment， and follow-up monitoring.

Objective:To investigate the effect of hypericin (Hyp) on neurologic impairment, ferroptosis and cuproptosis in mice with acute cerebral infarction.Methods:Sixty 8-week old male C57BL/6 mice were randomly divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, MCAO+Hyp low-dose treatment group (L-Hyp group), and MCAO+Hyp high-dose treatment group (H-Hyp group), with 15 mice in each group. Intraluminal filament MCAO models in the later 3 groups were established. Saline was given intraperitoneally into the sham-operated group and MCAO group, and Hyp was given intraperitoneally at 0.5 mg/kg or 1 mg/kg into the L-Hyp group and H-Hyp group 24 hours after modeling. Twenty-four hours after Hyp, neurologic function was assessed using Garcia score, grip strength test, and fatigue baton test; brain tissue edema was assessed by dry-wet weight method; neuronal necrosis, survival and apoptosis were detected by HE staining, Nissl staining and TUNEL, respectively; ferroptosis and oxidative stress were assessed using iron assay kit, and reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) assay kits; cuproptosis was assessed using copper assay kit and mitochondrial oxidative phosphorylation was evaluated by mitochondrial respiratory chain complex Ⅲ and Ⅳ activity detection kits; morphological changes in neuronal mitochondria after ferroptosis and cuproptosis were observed by electron microscopy; protein expressions of ferroptosis-associated solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), cuproptosis-associated solute carrier family 31 member 1 (SLC31A1), and ferredoxin 1 (FDX1) were detected by Western blotting.Results:(1) Compared with the MCAO group, the L-Hyp group and H-Hyp group had decreased modified Garcia score and brain water content, increased grip strength and rod-turning time, decreased number of necrotic and apoptotic neurons, increased number of survived neurons, decreased Fe 2+, ROS and MDA levels, increased GSH level and mitochondrial respiratory control rate, and decreased copper content, with significant differences ( P<0.05); and the above changes in the H-Hyp group were more obvious than those in the L-Hyp group, with significant differences ( P<0.05). Compared with the MCAO group, neurons in the L-Hyp group and H-Hyp group had significantly improved status in mitochondrial shrinkage, vacuolation, reduced cristulation, increased membrane density, ruptured cell membrane, endoplasmic reticulum damage and chromatin disruption ( P<0.05); and the H-Hyp group had signficantly more obvious improvement than the L-Hyp group ( P<0.05). (2) Compared with the MCAO group (0.38±0.09, 0.28±0.05), the L-Hyp group and H-Hyp group had significantly increased protein expressions of SLC7A11 and GPX4 (0.83±0.11, 0.49±0.06; 1.27±0.08, 0.84±0.04; P<0.05); the H-Hyp group had significantly higher SLC7A11 and GPX4 expressions than the L-Hyp group ( P<0.05). Compared with the MCAO group (2.76±0.17, 0.67±0.07), the L-Hyp group and H-Hyp group had significantly decreased protein expressions of SLC31A1 and FDX1 (1.72±0.07, 0.51±0.05; 1.12±0.06, 0.34±0.05; P<0.05); the H-Hyp group had significantly lower SLC31A1 and FDX1 expressions than the L-Hyp group ( P<0.05). Conclusion:Hyp can ameliorate ferroptosis and cuproptosis by regulating the protein expressions of SLC7A11, GPX4, SLC31A1 and FDX1, to alleviate oxidative stress injury in MCAO mice, thereby promoting the recovery of neurological function.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective To systematically evaluate and synthesize the experience and coping process of bowel symptoms in patients after sphincter-preserving surgery for rectal cancer,and to provide the evidence for the subsequent development of bowel symptom management strategies.Methods A comprehensive search was conducted across the Pubmed,Cochrane Library,CINAHL,Embase,Web of Science,CNKI,Wanfang Database,VIP Database and CBM Database for qualitative studies on the experience of bowel symptoms in post-sphincter-preserving surgery patients with rectal cancer.The search period was from database inception to October 2024.The quality of the included literature was assessed according to the Australian Joanna Briggs Institute Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research,and the results were synthesized through the aggregative integration method.Results 14 studies were included,yielding 52 research findings,which were grouped into 10 subcategories and further synthesized into 4 results:the physical and psychological experiences of patients with bowel symptoms;the impact of bowel symptoms on patients'daily lives;coping styles for bowel symptoms in patients;facilitators of patients bowel symptom coping.Conclusion Bowel symptoms have significant negative impacts on the lives of patients following sphincter-preserving surgery for rectal cancer,and healthcare professionals should address these patients'needs by developing effective symptom management strategies and supporting patients in enhancing self-management abilities to improve quality of life.

Objective:To investigate the predictive value of serum signal lymphocyte activation molecule family member 8(SLAMF8)levels for post-stroke cognitive impairment(PSCI).Methods:The GSE122063 dataset was selected from the Gene Expression Omnibus(GEO), and key genes associated with vascular dementia were identified using STRING network and Cytoscape software.This prospective cohort study involved 123 patients with acute cerebral infarction(ACI)who were admitted to the Department of Neurology at Jiangsu University Affiliated Hospital from January to December 2023.Patients were followed up for six months and categorized into PSCI and post-stroke non-cognitive impairment(PSNCI)groups based on the occurrence of PSCI.General data from both groups at baseline, as well as the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment Scale(MoCA)scores at the six-month follow-up, were collected.Baseline serum levels of SLAMF8 and stabilin-1(STAB1), along with serum levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)at the six-month follow-up, were measured.Pearson correlation analysis was used to assess the correlation between variables, while logistic regression analysis was employed to determine baseline factors influencing the occurrence of PSCI.Receiver Operating Characteristic(ROC)curves were plotted to analyze the predictive value of variables for PSCI occurrence.Results:The Cytoscape software identified SLAMF8 and STAB1 as key genes associated with vascular dementia, utilizing maximum neighborhood component density(DNMC)and eccentricity algorithms on the GSE122063 dataset.In the cohort study, patients in the PSCI group exhibited higher baseline NIHSS scores and serum SLAMF8 levels compared to the PSNCI group( t=3.033, 5.422; P<0.01). Additionally, they demonstrated significantly lower MMSE and MoCA scores( t=16.340, 18.634; P<0.001)and higher serum levels of IL-1β and IL-6( t=2.633, 2.632; P<0.05)at the 6-month follow-up.No significant difference was observed in baseline STAB1 levels between the two groups( t=1.280, P>0.05). In the PSCI group, there was no significant correlation between baseline serum SLAMF8 levels and admission NIHSS scores( r=0.257, P=0.082); however, SLAMF8 showed a negative correlation with both MMSE scores( r=-0.711, P<0.001)and MoCA scores( r=-0.686, P<0.001)at the 6-month follow-up.Logistic regression analysis indicated that baseline serum SLAMF8 levels( OR=1.142, P=0.001)and NIHSS scores( OR=1.094, P=0.007)were risk factors for the development of PSCI in patients with acute cerebral infarction(ACI). ROC curve analysis revealed that the area under the ROC curve(AUC)for baseline serum SLAMF8 levels in predicting PSCI occurrence in ACI patients was 0.776, while the AUC for the combined prediction using both SLAMF8 and NIHSS scores was 0.796.Furthermore, baseline serum SLAMF8 levels were positively correlated with serum IL-1β levels( r=0.652, P<0.001)and IL-6 levels( r=0.710, P<0.001)at the 6-month follow-up. Conclusions:The serum SLAMF8 level, exhibiting early high expression in ACI patients, may serve as a potential biological marker for predicting the occurrence of PSCI.

This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells(cDC1)and its therapeutic potential of modulating the nuclear factor kappaB(NF-κB)cells signaling pathway in non-small cell lung cancer(NSCLC).Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools,including the CIBERSORT algorithm,we analyzed the immune cell landscape within NSCLC tissues.Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells.Key differentially expressed genes(DEGs)and pivotal functional modules within these cells were identified,highlighting PU.1 as a critical mediator underexpressed in NSCLC samples.Functionally,PU.1 demonstrated the induction of the NF-κB pathway,which led to inhibited tumor proliferation and enhanced activation of cDC1,thereby suggesting its role in tumor immune surveillance.In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression,mediated through its influence on cDC1 functionality via the NF-κB pathway.These findings propose PU.1 as a promising target for NSCLC therapeutic strategies,emphasizing the importance of transcriptional regulators in the tumor microenvironment.

Rheumatic diseases are a group of chronic disorders characterized by abnormalities in the immune system,while portal hypertension occurs due to increased blood flow or heightened resistance in the portal venous system or obstruction of hepatic venous outflow.Both rheumatic diseases and their medications can lead to noncirrhotic portal hypertension.The hypercoagulable state associated with rheumatic diseases can result in thrombosis within the portal and hepatic venous systems,and damage to the intrahepatic portal system and hepatic sinusoidal endothelial system can lead to porto-sinusoidal vascular disease and hepatic sinusoidal obstruction syndrome.Moreover,drugs used for the treatment of rheumatic diseases may cause liver parenchymal injury,which further leads to liver fibrosis and cirrhosis,or they may damage the hepatic vascular endothelium and thus cause noncirrhotic portal hypertension.This article elaborates on the mechanisms and characteristics by which common rheumatic diseases and their therapeutic agents lead to portal hypertension,in order to provide insights and assistance for clinical diagnosis,treatment,and follow-up monitoring.

This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells (cDC1) and its therapeutic potential of modulating the nuclear factor kappaB (NF-κB) cells signaling pathway in non-small cell lung cancer (NSCLC). Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools, including the CIBERSORT algorithm, we analyzed the immune cell landscape within NSCLC tissues. Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells. Key differentially expressed genes (DEGs) and pivotal functional modules within these cells were identified, highlighting PU.1 as a critical mediator underexpressed in NSCLC samples. Functionally, PU.1 demonstrated the induction of the NF-κB pathway, which led to inhibited tumor proliferation and enhanced activation of cDC1, thereby suggesting its role in tumor immune surveillance. In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression, mediated through its influence on cDC1 functionality via the NF-κB pathway. These findings propose PU.1 as a promising target for NSCLC therapeutic strategies, emphasizing the importance of transcriptional regulators in the tumor microenvironment.

Objective: To investigate the attention cognitive function and symptom correlations of school aged children with attention deficit hyperactivity disorder (ADHD)using event related potential (ERP) technology, so as to provide references for the early diagnosis of children with ADHD. Methods: A total of 52 school aged children diagnosed with ADHD at the outpatient department of the Third Affiliated Hospital of Zhengzhou University from September 2022 to September 2024 and 50 age /sex matched healthy controls were selected. The ERP experiment adopted the auditory Oddball task to conduct comparative analyses of the amplitude and latency of the mismatch negative(MMN) at the Fz, Cz, and Pz points of the scalp electrode and the P3a component respectively. The symptom assessment scales adopted the Swanson,Nolan,and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ) and the Parent Symptom Questionnaire (PSQ), which were filled out by the parents. Spearman correlation analysis was used to analyze the correlation between ERP components and symptoms in schoolaged children with ADHD. Results: The latency of MMN components in the healthy control group on the Fz lead was (188.30±2.06)ms, and the amplitude was (-15.54±1.35)μV; the latency of the P3a component on the Pz lead was (312.82±7.80)ms, and the amplitude was (3.80±0.18)μV. The latency of MMN components in the ADHD group on the Fz lead was (188.94±1.39)ms, and the amplitude was (-14.78±1.40)μV; the latency of the P3a component on the Pz lead was (317.21±5.65)ms, and the amplitude was (3.70±0.13)μV. Compared with normal children, the MMN of children with ADHD had smaller amplitudes in the Fz and Cz leads, and the P3a had greater latency and smaller amplitudes in the Cz and Pz leads ( t =2.79,2.20；-2.04，-3.25；2.35,3.21， P <0.05). Correlation analysis showed that the latency of MMN in children with ADHD was positively correlated with the inattention score in the SNAP-Ⅳ( r =0.22), and the amplitude of MMN was negatively correlated with the inattention score in the SNAP-Ⅳ and the learning problem score in PSQ ( r = -0.26 , -0.34)( P <0.05). The latency of P3a was positively correlated with the scores of inattention in the SNAP-Ⅳ and the score of learning problems in the PSQ ( r =0.26 ,0.24); the amplitude of P3a was negatively correlated with the scores of attention deficit and hyperactivity/impulsivity in the SNAP-Ⅳ and the scores of learning problems and impulsivity/hyperactivity in the PSQ( r = -0.26 , -0.22, -0.25,-0.32)( P <0.05). Conclusions School aged ADHD children exhibit abnormal MMN/P3a components, indicating attention related cognitive dysfunction. Symptoms such as inattention, learning problems and hyperactivity/impulsivity in children with ADHD are related to abnormal components of MMN and P3a.