Hypersomnias of central origin are defined as the inability to maintain wakefulness and alertness during the major waking episodes of the day， with the manifestation of irrepressible drowsiness or even unprovoked sleep attacks. This spectrum of disorders mainly includes narcolepsy type 1， narcolepsy type 2， idiopathic hypersomnia， and Kleine-Levin syndrome. Currently， the clinical diagnosis of hypersomnias of central origin mainly depends on subjective medical history， sleepiness scales， and electrophysiological assessments， and these conventional diagnostic methods are easily affected by confounding factors. A reduction in the level of hypocretin-1 in cerebrospinal fluid （CSF） is the gold standard for the diagnosis of narcolepsy type 1， while there is still a lack of specific and Objective laboratory markers for the other subtypes， resulting in the high rates of diagnostic delay and misdiagnosis. As Objective and quantifiable indicators for pathophysiological processes， biomarkers have an important clinical value in the early screening， precise phenotyping， and longitudinal monitoring of hypersomnias of central origin， as well as in the development of targeted therapies for this group of sleep disorders. This article systematically reviews the research advances in biomarkers associated with hypersomnias of central origin from the five dimensions of polysomnography and daytime functional assessment， peripheral serology， cerebrospinal fluid， neuroimaging， and autonomic nervous function， in order to provide a theoretical framework and evidence-based support for constructing a precise diagnosis and treatment system for these disorders.
Narcolepsy

Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.

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.

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.

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.

Objective:To explore the death characteristics and disease burden of lung cancer in Chinese population from 2004 to 2021.Methods:A cross sectional study was conducted. The demographic data and lung cancer mortality surveillance data from 605 surveillance areas in the Chinese mortality surveillance dataset from 2004 to 2021 were used to calculate the crude death rate (CDR), potential years of life lost, average potential years of life lost, work years of potential life lost, and average work years of potential life lost for lung cancer in the population. Joinpoint model was used, and the trend of lung cancer mortality rates in different characteristic populations in the surveillance area was analyzed using average annual percentage change (AAPC) and annual percentage change (APC).Results:The CDR of lung cancer in the surveillance population of China from 2004 to 2021 was 42.94/100 000, with males having a higher CDR than females (58.94/100 000 vs. 26.92/100 000); the overall population, male and female lung cancer CDR showed an upward trend (AAPC were 2.70%, 3.20% and 1.85%, respectively), with a decreasing trend in the total population in 2004 and 2005 (APC = -1.04%), an increasing trend from 2006 to 2014 (APC = 4.46%), and an increasing trend from 2015 to 2021 (APC = 1.41%); the overall increase rate of lung cancer CDR in rural registered residence population (AAPC = 3.70%) was higher than that in urban registered residence population (AAPC = 1.30%). From 2004 to 2021, the age specific lung cancer CDR of the population in surveillance areas of China increased with age, reaching a peak of 437.77/100 000 in the population aged 85 years and above. From 2004 to 2021, the potential life loss caused by lung cancer in surveillance areas of China was 8 532 790.08 person years, with an average potential life loss of 6.55 years. Among them, females had a higher potential life loss than males (8.70 years vs. 4.30 years); the average potential work loss caused by lung cancer in males was 7.02 years, while in females it was 6.76 years. Conclusions:From 2004 to 2021, the overall mortality rate of lung cancer in China shows an upward trend, and the burden of lung cancer disease is relatively heavy. Male and elderly populations need to be given special attention.