Thymocyte selection-associated high mobility group box (TOX), a member of the high mobility group protein super-family, plays an important role in T cell development, functional maintenance, and exhaustion. It has been recently found that TOX exerts critical immunoregulatory functions during pathogen infections, and TOX expression is strongly associated with the intensity and tolerance of host immune responses. This review systematically summarizes the structural and functional features of TOX and focuses on its expression dynamics, mechanisms of action, and immunomodulatory effects during viral, bacterial, and parasitic infections, which provides a theoretical support to better understanding of the role of TOX in infectious diseases and provides new insights into development of potential immunotherapeutic strategies targeting TOX.

OBJECTIVE: To explore the application progress and clinical value of digital technologies in the surgical treatment of ankylosing spondylitis (AS). METHODS: By systematically reviewing domestic and international literature, the study summarized the specific application scenarios, operational procedures, and technical advantages of digital technologies [including preoperative three-dimensional (3D) planning, intraoperative real-time navigation, robot-assisted surgery, and 3D printing] in AS surgery, and analyzed their impact on surgical accuracy, complication rates, and clinical outcomes. RESULTS: Digital technologies significantly improve the precision and safety of AS surgery. Preoperative 3D planning enables personalized surgical protocols; intraoperative navigation systems dynamically adjusts surgical trajectories, reducing the risk of iatrogenic injury; robot-assisted surgery can minimize human errors and enhance implant positioning accuracy; 3D-printed anatomical models and guides optimize the correction of complex spinal deformities. Furthermore, the combined applications of these technologies shorten operative time, reduce intraoperative blood loss, decrease postoperative complications (e.g., infection, nerve injury), and accelerate functional recovery. CONCLUSION Through multidimensional integration and innovation, digital technologies provide a precise and minimally invasive solution for AS surgical treatment. Future research should focus on their synergy with biomaterials and intelligent algorithms to further refine surgical strategies and improve long-term prognosis.
Humans ; Spondylitis, Ankylosing/diagnostic imaging* ; Printing, Three-Dimensional ; Surgery, Computer-Assisted/methods* ; Robotic Surgical Procedures/methods* ; Imaging, Three-Dimensional ; Postoperative Complications/prevention & control* ; Digital Technology ; Models, Anatomic

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.
Humans ; Adult ; Postoperative Complications ; Erythrocyte Transfusion/adverse effects* ; Blood Transfusion ; Hospitals ; Hemoglobins/analysis*

Objective:To investigate the efficacy and cognitive function of 3 new antiepileptic drugs Oxcarbazepine (OXC), Lamotrigine (LTG) and Levetiracetam (LEV) in children with self-limited epilepsy with centrotemporal spikes (SeLECTS).Methods:This was a prospective study.A total of 98 children with SeLECTS who were treated in the Second Affiliated Hospital of Xinxiang Medical University from January 2014 to June 2020 were divided into OXC group, LTG group and LEV group according to the applied therapeutic drugs.Video electroencephalograph (EEG), Wechsler Intelligence Scale for Children (WISC) and event-related potentials (ERPs) of the children were collected before treatment and 48 weeks of treatment.Clinical efficacy and impact on cognitive function among the 3 groups were compared.Results:(1)Efficacy: There was no significant difference in the effective rate of seizure reduction after treatment among the 3 groups( χ2=0.808, P=0.668). There was no significant difference in EEG remission rate among the 3 groups( χ2=0.763, P=0.683). (2)Cognitive function: ①Intragroup comparison of WISC findings showed that the full scale score (FIQ) and verbal intelligence quotient (VIQ) were significantly enhanced, and the scores of comprehension, vocabulary, arithmetic, decoding and spelling subtests were more significantly enhanced in OXC group after treatment (all P<0.05). In the LTG group, FIQ, VIQ and operational intelligence quotient (PIQ) were significantly enhanced after treatment (all P<0.05), and the subtest scores of comprehension, vocabulary, arithmetic, mapping and layout were significantly enhanced (all P<0.05). In LEV group, FIQ, VIQ and PIQ were significantly enhanced after treatment (all P<0.05), especially the increase in the VIQ, and the scores of vocabulary, understanding, similarity, arithmetic, decoding and puzzle subtests were significantly enhanced (all P<0.05). Pairwise comparison of WISC findings showed that there were no significant differences in the FIQ, VIQ, PIQ and subtest scores before treatment among the 3 groups (all P>0.05). After treatment, the arithmetic and decoding scores of OXC group were significantly higher than those of LTG group (all P<0.05), which were comparable between OXC group and LEV group (all P>0.05). The PIQ and the scores of mapping and layout in LTG group were significantly higher than those of the other 2 groups (all P<0.05). The LEV group had higher scores in vocabulary, comprehension and spelling than those of the other 2 groups (all P<0.05), which had higher decoding scores than those of the LTG group (all P<0.05). No significant differences were found in decoding scores between LEV and OXC group (all P>0.05). Higher VIQ and FIQ were detected in LEV group than those of the other 2 groups (all P<0.05). ②Intragroup comparison of ERPs showed that the latency of LEV group after treatment was significantly shorter than that before treatment ( P<0.05), and there was no significant difference between the other 2 groups before and after treatment (all P>0.05). Pairwise comparison of ERPs showed that before treatment, there were no significant differences in P300 amplitude and latency among the 3 groups (all P>0.05). After treatment, the latency of LEV group was significantly shorter than that of the other 2 groups ( P<0.05), and there was no significant difference in the amplitude between the 3 groups before and after treatment ( P>0.05). Conclusions:(1)In the treatment of SeLECTS in children, OXC, LTG and LEV have reliable and equivalent effects.(2)OXC, LTG and LEV have protective effects on cognitive function in children with SeLECTS.After treatment, LEV provides the strongest protective effect on FIQ, and the protective effect on VIQ is equivalent to OXC, but better than LTG.LTG is superior in protecting spatial perception and PIQ.

Objective To explore the changes of serum amyloid A (SAA) level and its clinical significance in patients with post-stroke depression (PSD). Methods One hundred and sixty-four patients with acute ischemic stroke, admitted to our hospital from January 2016 to June 2017 were assessed with Hamilton Depression Scale-17 (HAMD-17) to evaluate the depression degrees, and accordingly, they were divided into PSD group (n=57) and non-PSD group (n=107). Healthy volunteers who were examined in the corresponding period were selected as healthy control group (n=50). The SAA level was determined with ELISA in subjects of the 3 groups. Clinical data were collected; single factor analysis and multivariate Logistic regression analysis were performed to select the risk factors of PSD. Results The SAA level in PSD group ([18.85±5.25] mg/L) was significantly higher than that in the non-PSD group ([15.25±5.75] mg/L) and healthy control group ([7.65±4.50] mg/L, P<0.05); that in the non-PSD group was significantly higher than that in the healthy control group (P<0.05). Single factor analysis showed that differences in education level, introversion, economic status, living alone, marital status, National Institutes of Health Stroke Scale (NIHSS) scores≥9 at admission, complications, and proportion of key area infarction (frontal lobe and basal ganglia) had statistical significance between PSD group and non-PSD group (P<0.05). Multivariate Logistic regression analysis showed that introversion, poor economic status, living alone, NIHSS scores≥9, infarction of key areas, and elevation of SAA level (OR=1.545, P=0.035, 95％ CI: 1.257-1.898) were independent risk factors for PSD (P<0.05). Conclusion SAA used as one of the detection biomarkers has great significance in early diagnosis, intervention and clinical prevention for PSD.

Objective To explore the rapid eye movement (REM) sleep characteristics of different episode types of depression and post-stroke depression (PSD) patients and provide support for clinical diagnosis,treatment and prognosis.Methods Patients with single-episode depression (group A,n =22),patients with recurrent depression (≥ 2 episodes,group B,n=26) and patients with PSD (group C,n=19)were included from Henan Provincial Mental Hospital.20 healthy volunteers were assigned to control group.Participants in the 4 groups were performed polysomnographic recordings (PSG) from 9 PM to 6 AM before treatment.The 3 patients groups were performed the second PSG recordings and HAMD score at the end of 6 week SSRIs treatment.The REM indexes of 4 groups were compared and analyzed.Results First PSG detection showed that REM sleep latencies (RL) were shorter in group A and B (A:(65.57±18.29) min,B:(66.32±15.46) min) than that in group C ((79.17±20.18) min) and control group((87.24±16.55)min);REM activity (RA) (A:(99.82±25.71) u,B:(104.70±28.23) u)and REM density (RD) (A:(81.06± 19.35)％,B:(86.61±23.83) ％) were increased more significantly in group A and B than those in control group ((79.61 ± 18.40) u;(68.11 ± 17.54) ％);REM sleep time (RT) were decreased more signifi-cantly in group C ((51.66±22.26) min) than that in group A((71.43±20.70) min),group B((74.81±17.52) min) and control group ((70.46±16.35) min)(P＜0.05).After treatment,REM sleep latency was prolonged in group A ((65.57±18.29) min vs (81.71±21.62) min),and REM activity was decreased in group A((99.82±25.71) u vs (83.58±27.19) u),the difference was statistically significant (P＜0.05).REMdensity was decreased,but the difference was not statistically significant (P＞0.05).There was no significant difference in the indexes of REM in group C;RT was prolonged ((51.66± 22.26) min vs (68.37 ± 20.16)min) in group C,the difference was statistically significant (P＜0.05).Conclusion Most of depression patients with different episode types have REM disinhibition phenomenon.RD increase may be REM characteristic type of depression patient.Sleep disorders of PSD patients are mainly poor sleep process and sleep continuity and have no characteristics of REM sleep disorder of depression ones.