Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Objective:To investigate the hepatoprotective effect of N-acetylcysteine(NAC)on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-kappa B(NF-κB).Methods:Male Sprague-Dawley rats were randomly divided into control group(CG),cisplatin group(CP),and NAC group.The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days.At half an hour after intragastric administration on the fifth day,all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury.An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),and total bilirubin(TBIL);liver index was calculated for the rats;Western blot was used to measure the relative expression levels of NF-κB,IL-6,and TNF-α in liver tissue;the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.Results:Compared with the NC group,the CP group had significant increases in the content of AST,ALT,ALP,and TBIL,while NAC reversed the abnormal liver function caused by cisplatin.Compared with the NC group,the CP group had a sig-nificant increase in liver index(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=0.007).Compared with the NC group,the CP group had signifi-cant increases in the expression levels of IL-6,TNF-α,and NF-κB,while the NAC group showed reductions in the expression of these genes,with significant differences in the expression of IL-6 and TNF-α(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in the α-diversity index of intesti-nal flora,while compared with the CP group,the NAC group tended to have a reduction in the α-diversity index of intestinal flora.Com-pared with the CP group at the phylum level,the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes.Compared with the CP group at the genus level,the NAC group had a reduction in the abundance of Rumino-coccaceae and increases in the abundance of Bifidobacterium and Allobaculum.Conclusion:NAC can alleviate acute liver injury caused by cisplatin,possibly by downregulating the expression of IL-6,TNF-α,and NF-κB and regulating the abundance and diver-sity of intestinal flora.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Objective To develop a virtual reality rehabilitation support system and evaluate its effects on improving discharge readiness in caregivers of laryngectomy patients.Methods The system is equipped with a virtual reality-based home nursing skills guidance module for post-laryngectomy patients and an evidence-based artificial intelligence Q&A module.A convenience sampling method was adopted to select 64 caregivers of patients who underwent laryngectomy for the first time in the otorhinolaryngology head and neck surgery department of a tertiary A hospital in Beijing from July 2024 to January 2025 for a systematic study on application effects.To avoid cross-contamination between an experimental group and a control group,ward-based grouping was applied.A coin toss was used to assign Ward 1 to an experimental group and Ward 2 to a control group,with 32 cases in each group.The experimental group received discharge guidance based on the virtual reality technology,while the control group was provided with conventional verbal and written discharge instructions.The readiness for hospital discharge and the quality of discharge teaching scores of caregivers were compared between the 2 groups after the intervention.Results No sample detachment.After the intervention,the patient caregivers in the experimental group scored significantly higher than those in the control group in terms of discharge readiness and quality of discharge guidance,with a statistically significant difference(P＜0.001).Conclusion This study developed the virtual reality rehabilitation system for laryngeal cancer patients demonstrated good feasibility and effectiveness.The application of this system for discharge education significantly improved discharge readiness of caregivers and quality of discharge guidance for post-laryngectomy patients.It also helped with the optimization of health education models,enhancement of nursing resource utilization efficiency,and improvement of transitional care.

Stroke is characterized by a high disability rate. After stroke, patients will have different degrees of limb dysfunction, which seriously affects their quality of life. In recent years, fully immersive virtual technology has been gradually applied at home and abroad to promote limb function rehabilitation of stroke patients. This paper reviews the technical components, application forms, application effects, prospects and challenges of fully immersive virtual reality technology in limb function rehabilitation of stroke patients, in order to provide theoretical basis for the subsequent application of fully immersive virtual reality technology to improve the level of limb function rehabilitation of stroke patients.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective To explore the effects and therapeutic mechanism of electroacupuncture on the levels of polarization markers and inflammatory factors interleukin(IL)-6,IL-4,tumor necrosis factor-alpha(TNF-α),and IL-10 in rats with para-chlorophenylalanine-induced insomnia(PCPA).Methods Fifty healthy specific-pathogen free grade Sprague-Dawley rats,half male and half female,were randomly divided into a blank group(n=10)and a model reserve group(n=40),in which insomnia was induced by intraperitoneal injection of a 500 mg/kg PCPA suspension.Using the random number table method,the 30 successfully modeled rats were divided into three treatment groups of 10 rats/group:model,electroacupuncture,and estazolam.The estazolam group was given estazolam 0.2 mg/(kg·d)by gavage;the electroacupuncture group was given once-daily electroacupuncture at the"Shenmen"and"Sanyinjiao"acupoints,and stimulation at the"Baihui"and"Benshen"acupoints,20 minutes each time,for 7 consecutive days.Following treatment,serum and hypothalamic levels of TNF-α,IL-6,IL-4,and IL-10 were detected using ELISA and Western blot,while immunofluorescence staining was used to detect the presence of Iba-1 in hypothalamic microglia and the co-expression of CD86 and CD163,which are markers for the M1 and M2 subtypes of microglial cells,respectively.Results Compared with the blank group,the model group exhibited prolonged sleep latency(SL)(P＜0.01),shortened sleep duration(ST)(P＜0.05),significantly higher serum and hypothalamic protein levels of IL-6 and TNF-α(P＜0.01),and significantly lower levels of IL-4 and IL-10(P＜0.01).Compared with the model group,the electroacupuncture and estazolam groups exhibited significantly shorter SL(P＜0.01),prolonged ST(P＜0.01),significantly lower serum and hypothalamic protein levels of IL-6 and TNF-α(P＜0.01),and significantly higher IL-4 and IL-10 levels(P＜0.01).IL-6 content was lower in the electroacupuncture group than in the estazolam group(P＜0.05).Compared with the blank group,the model group exhibited significantly enhanced Iba-1/CD86(M1 type)co-expression(P＜0.01)alongside significantly weakened Iba-1/CD163(M2 type)co-expression(P＜0.01).Under electroacupuncture or estazolam intervention,Iba-1/CD86 co-expression was significantly weakened(P＜0.01),and Iba-1/CD163 co-expression was significantly enhanced in the model group(P＜0.05).Conclusions Electroacupuncture effectively improved sleep disturbances in rats,with an underlying mechanism that may involve regulation of microglial polarization,downregulation of pro-inflammatory cytokine levels,upregulation of anti-inflammatory cytokine levels,and alleviation of neuroinflammation,thereby ameliorating sleep.

Objective To explore the impact of irregular shape of head CT hematomas on postoperative re-bleeding and prognosis of patients with spontaneous intracerebral hemorrhage(ICH)who undergo craniotomy for hematoma evacuation.Methods We retrospectively enrolled consecutive patients with ICH who underwent craniotomy for hematoma evacuation in the Department of Neurosurgery of the Second People's Hospital of Guiyang Affiliated to Guizhou Medical University from January 2019 to June 2024.Baseline and clinical data were collected form the patients,including age,gender,smoking history,drinking history,hypertension,diabetes,history of anticoagulant use,admission systolic and diastolic blood pressure,admission National Institutes of Health stroke scale(NIHSS)score,Glasgow coma scale(GCS)score,time from onset to the first head CT,neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).Admission head CT scans were used to assess hematoma shape(regular or irregular),hematoma location(basal ganglia,lobar,multifocal),hematoma volume,perihematomal edema volume,the presence of midline shift,and intraventricular extension.Volume of the hematoma was assessed 2 days after surgery.Postoperative re-bleeding is defined as an increase in the volume of the hematoma by 12.5 ml compared to the previous postoperative CT scan within 2 weeks after surgery,or the reappearance of high-density areas in the focal area of the head CT scan during follow-up after complete hematoma clearance.Conduct patients follow-ups via telephone at 6 months postoperatively to assess their modified Rankin scale(mRS)scores.The sliding dichotomy method was applied to define prognosis based on the patients' baseline characteristics and disease severity.The prognostic score was calculated using formula:10 × admission GCS score-age-0.64 × admission hematoma volume.A prognostic score＞27.672 was considered potentially favorable,while a score ≤ 27.672 was considered potentially unfavorable.For patients with a potentially favorable prognosis,an mRS score of 0-2 was defined as a good outcome,and a score of 3-6 as a poor outcome.For those with a potentially unfavorable prognosis,an mRS score of 0-3 was defined as a good outcome,and a score of 4-6 as a poor outcome.In the comparison of baseline and clinical data between patients with regular and irregular hematoma shapes,factors with P＜0.05 were included in propensity score matching(PSM)to adjust for confounding variables.A 1∶1 matching was performed using the nearest neighbor method with a caliper value set to 0.25.Variables with statistically significant differences between groups after PSM matching were included in the multivariate Logistic regression analysis to identify influencing factors for postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy hematoma evacuation.The predictive value of irregular hematoma shape for postoperative rebleeding and poor prognosis in ICH patients was analyzed using receiver operating characteristic(ROC)curve analysis.Results(1)A total of 440 ICH patients were enrolled,including 342 males and 98 females,aged from 20 to 84 years with a mean age of(56±12)years.Statistically significant differences were observed in baseline and clinical data between patients with regular and irregular hematoma shapes before PSM,including age,admission GCS score,NIHSS score,NLR,proportion of patients with hematoma rupture into ventricles,preoperative hematoma volume,proportion of patients with midline shift,preoperative volume of hematoma surrounding edema,proportion of patients with hematoma located in multiple sites,and postoperative 2-day hematoma volume(all P＜0.05).After propensity score matching of these factors,298 ICH patients were included in the statistical analysis,comprising 228 males and 70 females,with an age range of 20 to 84 years and a mean age of(57±12)years.Following PSM,no statistically significant differences were observed in the baseline and clinical characteristics between patients with irregular and regular hematoma shapes(all P＞0.05).(2)After propensity score matching,28 patients experienced postoperative re-bleeding while 270 did not.Significant differences were observed between the two groups in the following factors:proportion of patients with a history of anticoagulant use,admission PLR,NLR,irregular hematoma shape,and hematoma volume at 2 days after operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using postoperative re-bleeding as the dependent variable and incorporating factors with P＜0.05 from the univariate analysis as independent variables,multivariate Logistic regression analysis identified irregular hematoma shape(OR,2.821,95％CI 1.142-6.968,P=0.025)and larger hematoma volume at 2 days post-operation(OR,1.062,95％CI 1.026-1.099,P＜0.01)as independent risk factors for re-bleeding following intracranial hematoma evacuation in ICH patients.ROC curve analysis demonstrated that irregular hematoma shape predicted postoperative re-bleeding with an area under the curve(AUC)of 0.62,showing a sensitivity of 71.4％and a specificity of 52.2％.(3)After propensity score matching,174 patients had poor prognosis while 124 had good prognosis.Significant intergroup differences were observed in age,admission GCS score,NIHSS score,irregular hematoma shape,proportion of patients with hematomas located in the basal ganglia and cerebral lobes,and hematoma volume at 2 days post-operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using poor prognosis as the dependent variable and incorporating factors with P＜0.05 from univariate analysis as independent variables,multivariate Logistic regression analysis revealed that advanced age(OR,1.039,95％CI 1.015-1.064,P=0.002),high admission NIHSS score(OR,1.068,95％CI 1.025-1.113,P=0.002),irregular hematoma shape(OR,2.675,95％CI 1.582-4.524,P＜0.01),and larger hematoma volume at 2 days post-operation(OR,1.033,95％CI 1.002-1.064,P=0.038)were independent risk factors for poor prognosis.Conversely,lobar hematoma location(OR,0.192,95％CI 0.073-0.504,P＜0.01)was identified as a protective factor.ROC curve analysis showed that irregular hematoma shape predicted poor prognosis after intracranial hematoma evacuation with an AUC of 0.61,demonstrating a sensitivity of 59.2％and specificity of 62.9％.Conclusion Irregular hematoma shape on head CT is an independent risk factor for both postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy for hematoma evacuation.