Objective: To investigate the effect of integrin α5 on the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in periodontal ligament fibroblasts (PDLFs) within an inflammatory microenvironment. Methods: This study was approved by the Ethics Committee of Laboratory animals. After rat PDLFs were treated with LPS (0.5, 5, and 50 µg/mL) for 24 h, the primary medium was discarded and replaced with serum-free culture medium. After 24 h, the supernatant was collected and mixed with DMEM medium containing 10% exosome-free serum at a volume ratio of 1:1 to obtain conditioned medium (CM). The groups were labeled as the 0.5-CM, 5-CM, and 50-CM groups. In addition, PDLFs cultured in DMEM medium containing 10% exosome-free serum were considered the 0-CM group. PDLFs were cultured with the above CM. In the inhibitor group, PDLFs were cultured in 0-CM containing different concentrations of integrin α5 inhibitor ATN-161 (0, 0.025, 0.25, 2.5, 25, and 250 μg/mL). The effect of CM and integrin α5 inhibitor ATN-161 on cell viability was assessed using the CCK-8 assay. According to the CCK-8 results, in further inhibitor intervention experiments, PDLFs were cultured in 0-CM, 5-CM (without/with 25 μg/mL ATN-161), and 0-CM containing 25 μg/mL ATN-161, which were labeled as the 0-CM, 5-CM, ATN-161+5-CM, and ATN-161 groups, respectively. The expression changes of integrin α5 and NLRP3 were detected using Western blot and qRT-PCR techniques. For in vivo experiments, 24 rats were randomly divided into four groups (n=6). The control group contained healthy rats that received no treatment. The rats in the other three groups were injected with 40 µL of 0-CM containing 25 μg/mL ATN-161 or 5-CM (without or with 25 μg/mL ATN-161) on the palatal side of the left maxillary first molar every three days; these groups were classified as the ATN-161, 5-CM, and ATN-161+5-CM groups, respectively. On the 30th day, the left maxillary tissue of rats was used for Micro-CT, HE staining, and immunohistochemical detection. Results : The CCK-8 assay showed that CM, 25 μg/mL ATN-161, and ATN-161 concentrations below 25 μg/mL had no significant effect on cell viability at 12 h and 24 h (P > 0.05). 50-CM and 25 μg/mL ATN-161 significantly inhibited cell viability at 48 h (P < 0.05). For in vitro experiments, compared to the 0-CM group, both the protein and mRNA levels of integrin α5 and NLRP3 were significantly increased in rat PDLFs in the 5-CM group (P < 0.05). Intervention with 25 μg/mL ATN-161 significantly attenuated the enhancement of 5-CM on the expression of integrin α5 and NLRP3 (P < 0.05). For in vivo experiments, compared to the control group, alveolar bone resorption and periodontal inflammatory cell infiltration were significantly increased in the 5-CM and ATN-161+5-CM groups, and the expression of integrin α5 and NLRP3 was significantly increased (P < 0.01). However, compared to the 5-CM group, the ATN-161+5-CM group had less alveolar bone resorption and fewer periodontal inflammatory cells. Further, the expression of integrin α5 and NLRP3 was significantly reduced (P < 0.01). Conclusion In vitro and in vivo experiments showed that integrin α5 mediated NLRP3 expression in PDLFs under an inflammatory microenvironment. ATN-161 inhibited the expression of integrin α5, thus significantly downregulating the expression of NLRP3, which plays a role in inhibiting inflammation.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

Rapid eye movement sleep behavior disorder （RBD） is a type of parasomnia closely associated with neurodegenerative diseases related to α-synucleinopathies， such as Parkinson disease， dementia with Lewy bodies， and multiple system atrophy， and early diagnosis is of great importance for disease monitoring and intervention.At present， RBD is mainly diagnosed based on video polysomnography （v-PSG） and nocturnal abnormal behaviors， but the application of v-PSG is limited by its high technical demands.Various validated RBD-related scales have become essential tools for auxiliary diagnosis， which provides methods and tools for the diagnosis of RBD and the assessment of disease progression and outcomes.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Disorders of consciousness（DoC） refer to the state of loss of consciousness caused by various severe brain injuries， and there is still a lack of widely recognized effective treatment methods for DoC at present. As a promising neuromodulation technique， vagus nerve stimulation（VNS） has shown significant potential in promoting the recovery of consciousness through various mechanisms such as the modulation of key neural network activities. This review systematically elaborates on the potential mechanism of VNS in the treatment of DoC and comprehensively evaluate the evidence for its clinical efficacy. At first， this article introduces the technical principles of VNS and the clinical classification of DoC， and then it delves into the mechanisms by which VNS promotes the recovery of consciousness， including modulation of neural networks， activation of the ascending reticular activating system， regulation of neurotransmitter balance， suppression of inflammatory responses， and enhancement of neuroplasticity.Finally， it systematically reviews existing clinical studies， including those on invasive VNS and transcutaneous auricular vagus nerve stimulation （taVNS）， and discusses the limitations of current research and the directions for future development. This review shows that VNS， especially noninvasive taVNS， is expected to become a new therapeutic strategy for DoC， although large-scale randomized controlled trials are needed to validate its clinical efficacy.

Objective:To evaluate the pharmacodynamics of remimazolam tosilate inducing loss of consciousness (LOC) when combined with sufentanil in children.Methods:American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ pediatric patients of either sex, aged 3-6 yr, undergoing electronic bronchoscopy, were included in this study. ECG monitoring was carried out in all children after admission, sufentanil 0.1 μg/kg was intravenously injected slowly, and 3 min later remidazolam tosilate was intravenously injected. The dose of remimazolam tosilate was determined by the modified Dixon′s up-and-down sequential experiment, and the initial dose of remimazolam tosilate was 0.30 mg/kg. The dose of remimazolam tosilate in the next child was determined according to the the loss of consciousness, and the successive dose gradient was 0.05 mg/kg. Loss of eyelash reflex and Modified Observer′s Assessment of Alertness/Sedation Scale score reaching 0 and the occurrence of 8 crossover points where consciousness transitioned from non-disappearance to disappearance after 1 min of remimazolam tosilate injection were considered to be signs of LOC. The median effective dose (ED 50), 95% effective dose (ED 95), and their 95% confidence interval ( CI) of remimazolam tosilate inducing LOC were calculated using probit method. Results:When combined with sufentanil, the ED 50 and 95% CI of remimazolam tosilate inducing loss of consciousness were 0.461 (0.429-0.493) mg/kg, and the ED 95 and 95% CI were 0.515 (0.487-0.689) mg/kg. Conclusions:When combined with sufentanil, the ED 50 of remimazolam tosilate inducing LOC is 0.461 mg/kg and the ED 95 is 0.515 mg/kg in children.

【Objective】 To investigate the relationship between the initial serum ammonia level and the risk of ICU and hospital mortalities in critically ill patients without hepatic disease. 【Methods】 A retrospective cohort study was conducted among patients admitted to the eICU Collaborative Research Database (eICU-CRD) for a single admission who had serum ammonia test records within 48 hours of the first ICU admission and had no hepatic disease. The age, sex, ethnicity, Acute Physiologic and Chronic Health Evaluation Ⅳ score (APACHE Ⅳ score), treatment methods, complications, and outcomes were extracted. Univariable and multivariable Logistic regression were used to analyze the relationship between serum ammonia level and the risk of mortality. Interactions were used to analyze whether the relationship between serum ammonia level and the risk of mortality differed in subgroups of APACHE Ⅳ scores, age, sex, and ethnicity; subgroup analyses were made. 【Results】 A total of 1 674 patients were included. The multivariable Logistic regression showed that for every 10 μg/dL increase in ammonia, the risk of ICU death increased by 6.9% (OR=1.069, 95% CI: 1.036-1.104), and the risk of hospital death increased by 4.6% (OR=1.046, 95% CI: 1.017-1.076). The risk of ICU death was 1.7 times greater in patients with initial ammonia level of 49-82 μg/dL than in those with <49 μg/dL (OR=1.700, 95% CI: 1.165-2.482), the risk of ICU death was 2.862 times greater in patients with a level of ≥82 μg/dL compared to those with <49 μg/dL (OR=2.862, 95% CI: 1.792-4.570), and the risk of hospital death was 1.844 times higher in the ≥82 μg/dL group than in the <49 μg/dL group (OR=1.844, 95% CI: 1.213-2.804). There were no significant differences between initial ammonia level and the risk of mortalities in different subgroups of APACHEⅣ scores, age, sex, or ethnicity. 【Conclusion】 In critically ill patients without hepatic disease, elevated initial serum ammonia level after ICU admission is associated with a high risk of ICU and hospital mortality.

Objective To evaluate the efficacy and safety of midazolam combined with dexmedetomidine for sedation during magnetic resonance imaging(MRI)examination in children.Methods The medical records of children who underwent sedated MRI examinations at the Sedation Center of Children's Hospital Affiliated to Shandong University from August 2021 to July 2022 were collected.The patients were divided into three groups based on age:Infant group(age≤1 year old,922 cases),toddler group(1 year old