Primary cilia—those solitary, microtubule-based projections extending from the surface of most eukaryotic cells—are increasingly recognized not merely as cellular appendages, but as sophisticated signaling hubs. By compartmentalizing specific receptors (e.g., GPCRs) and effectors within a microdomain guarded by the transition zone, these organelles function effectively as high-gain sensors capable of integrating mechanical stimuli with metabolic cues. In this review, we examine the pivotal role of primary cilia across the nervous, bone-vascular, and renal landscapes, arguing for a unified “mechano-metabolic coupling” framework. Here, conserved ciliary modules are not static; rather, they are differentially deployed to uphold systemic homeostasis. Within the central nervous system, we position primary cilia as upstream integrators. We highlight how hypothalamic neuronal cilia concentrate metabolic receptors, such as the melanocortin 4 receptor (MC4R), to interpret energy status. Moreover, the recent identification of serotonergic “axon-cilium synapses” points to a direct mode of neurotransmission, wherein 5-HT6 receptors drive nuclear signaling and chromatin accessibility to rapidly modulate gene expression. Through these mechanisms, central cilia modulate sympathetic tone and neuroendocrine output, effectively establishing the mechanical and metabolic “boundary conditions” under which peripheral organs operate. Dysfunction in these central hubs is linked to obesity and neurodevelopmental disorders, including Bardet-Biedl syndrome. In peripheral tissues, cilia serve as versatile mechanotransducers that convert physical forces into biochemical responses. Regarding the bone-vascular system, we discuss the translation of mechanical loads and fluid shear stress into structural remodeling. In osteoblasts, specifically, ciliary integrity is intrinsically linked to cholesterol and glucose metabolism, fine-tuning the balance between Hedgehog and Wnt/β-catenin signaling to govern osteogenesis and bone repair. A similar dynamic exists in the vasculature, where endothelial cilia sense shear stress to modulate KLF4 expression and endothelial-to-mesenchymal transition—processes critical for valvulogenesis and vascular remodeling. Meanwhile, in the kidney, tubular cilia act as terminal effectors within a “shear-cilia-metabolism” axis. Here, fluid shear stress engages ciliary signaling to trigger AMPK-mediated lipophagy and mitochondrial biogenesis, thereby securing the ATP supply required for solute transport. Notably, dysregulation of this axis leads to metabolic reprogramming and aberrant proliferation, acting as a hallmark driver of cystogenesis in polycystic kidney disease (PKD). Crucially, this review attempts to dissect the often-conflated logic of cross-system integration by distinguishing 3 non-equivalent pathways: direct communication via ciliary extracellular vesicles, though this remains largely hypothetical in long-range signaling; “physiology-mediated cascades”, where ciliary dysfunction in a single organ—such as the kidney—precipitates systemic pathology through hemodynamic and metabolic shifts (e.g., altered blood pressure, fluid volume, or uremic toxins); and “parallel molecular defects”, where shared genetic mutations in ubiquitous components like the IFT machinery cause simultaneous, independent failures across multiple organ systems. Building on these distinctions, we propose a nested-loop model that links central set-points with peripheral feedback via physiological variables. Furthermore, we construct a “causality-to-translation” roadmap that pinpoints structural repair (e.g., targeting IFT assembly) and metabolic rescue (e.g., AMPK activation or autophagy induction) as promising therapeutic avenues. Ultimately, this framework provides a theoretical basis for deciphering the shared pathological mechanisms of multisystem ciliopathies, offering a strategic guide for the development of targeted interventions that go beyond symptomatic treatment.

This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*

OBJECTIVE: To investigate the metabolic characteristics of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in myeloid leukemia by in vitro culture of myeloid leukemia cells and construction of tumor-bearing nude mouse model. METHODS: U937, THP-1, HL60 and K562 cells were cultured in vitro. The cells in logarithmic growth phase (l×10 ⁵ cells/well) were added with ¹⁸F-FDG, and the uptake rate of ¹⁸F-FDG was measured at 15, 30, 60 and 120 min after addation, respectively. The four kinds of cells were inoculated subcutaneously into the hind limbs of nude mice to establish a tumor-bearing nude mouse model. When the tumor size was about 500 mm³, ¹⁸F-FDG was injected through the tail vein of the mice, and positron emission tomography/computed tomography was performed at 60 min after injection. The morphology of tumor-bearing cells was observed by hematoxylin-eosin (HE) staining in serial pathological sections. RESULTS: After co-incubation with ¹⁸F-FDG, the ¹⁸F-FDG uptake rates of U937 cells were significantly higher than THP-1, HL60 and K562 cells at 4 time points (all P <0.05), and THP-1 cells were higher than K562 cells (all P <0.05). The uptake rate of ¹⁸F-FDG by leukemia cells was rapid in the first 60 min, then tended to be stable. Pathological analysis showed that subcutaneous inoculation of U937, THP-1, HL60 and K562 cells could successfully establish tumor-bearing nude mouse models of myeloid leukemia. The ¹⁸F-FDG uptake value in U937 tumor-bearing nude mice was significantly higher than THP-1, HL60 and K562 tumor-bearing nude mice (all P <0.01). The ¹⁸F-FDG uptake values in THP-1 and HL60 tumor-bearing nude mice were significantly higher than that in K562 tumor-bearing nude mice (both P <0.01). CONCLUSION The tumor-bearing nude mouse model of myeloid leukemia can be successfully constructed by subcutaneous inoculation. The ¹⁸F-FDG uptake rate of acute myeloid leukemia (AML) cells is higher in cells cultured in vitro and tumor-bearing nude mouse model. ¹⁸F-FDG may have better clinical application value for AML.
Animals ; Fluorodeoxyglucose F18/metabolism* ; Mice, Nude ; Mice ; Humans ; Leukemia, Myeloid/diagnostic imaging* ; HL-60 Cells ; K562 Cells ; Cell Line, Tumor ; U937 Cells

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Objective To compare the analgesic effects and adverse reactions between intercostal nerve block (ICNB) and patient controlled intravenous analgesia (PCIA). Methods From August 2022 to January 2023, 180 patients with lung cancer who underwent thoracoscopic surgery were randomly divided into two groups: ICNB group (n=90) and PCIA group (n=90). The postoperative pain degree (VAS), location, nature; adverse events, such as nausea, vomiting, and dizziness; and other clinical symptoms were analyzed. Results The most common site of postoperative pain in both groups was surgical incision, and the nature of pain was distending pain. At 12 and 24 h after the operation, the pain degree in the ICNB group (1.10±0.91, 3.12±1.29) was markedly lower than that in PCIA group (1.44±0.86, 4.32±1.30, P=0.010, P<0.001). The incidence of nausea, vomiting, and dizziness in the ICNB group (5.56%, 23.33%) was noticeably lower than that in the PCIA group (35.56%, 51.11%, P<0.001, P<0.001). Total hospitalization expense in the ICNB group (41 043.16±10 885.63 yuan) was significantly lower than that in PCIA group (45 283.99±11 036.36 yuan, P=0.010). Conclusion The analgesic effect of intercostal nerve block is better than that of patient-controlled intravenous analgesia pump in patients with lung cancer after minimally invasive surgery, and the incidence of adverse reactions is low.

Objective To analyze the changes of neutrophil-to-albumin ratio(NPAR),monocyte-to-lymphocyte ratio(MLR),neutrophil-to-lymphocyte ratio(NLR)and interleukin-17A(IL-17A)in patients with severe autoimmune encephalitis(AE)and the predictive value of their combined detection for prognosis.Methods A total of 105 patients with severe AE admitted from May 2021 to April 2025 were selected as the severe group.During the same period,35 patients with mild-to-moderate AE and 35 healthy controls were enrolled in a 3:1:1 ratio as the mild-to-moderate group and control group respectively.The levels of NPAR,MLR,NLR and IL-17A were compared among the three groups.Patients with severe AE were observed for one month.According to the prognosis of patients,they were divided into poor prognosis subgroup[modified Rankin scale(mRS)score≥3,n=31]and good prognosis subgroup(mRS score<3,n=74).The levels of NPAR,MLR,NLR and IL-17A in the two groups were compared,to analyze the correlation between NPAR,MLR,NLR and IL-17A levels and mRS score in patients with severe AE,and to evaluate the predictive value of combined detection of the four indicators for prognosis in these patients.Results The levels of NPAR,MLR,NLR and serum IL-17A in mild-to-moderate group and severe group were higher than those in control group,which were higher in the severe group than in the mild-to-moderate group(P<0.05).The course of disease in the poor prognosis group was longer than that in the good prognosis group,and the proportion of patients with γ-aminobutyric acid B receptor antibody and the levels of NPAR,MLR,NLR and serum IL-17A were higher than those in the good prognosis group(P<0.05).Higher levels of NPAR,MLR,NLR and serum IL-17A were all risk factors for poor prognosis of patients with severe AE(OR=2.445,4.319,2.502,1.791,P<0.05).The levels of NPAR,MLR,NLR and serum IL-17A were positively correlated with the mRS score of patients with severe AE(r=0.546,0.519,0.554,0.561,P<0.001).The area under the receiver operating characteristic(ROC)curve(AUC)of NPAR,MLR,NLR and IL-17A detected in combination in predicting the prognosis of patients with severe AE was higher than that of the four indicators detected alone(P<0.05).Conclusion The changes in NPAR,MLR,NLR and IL-17A levels in patients with AE were closely related to the severity and prognosis of the disease.In the meantime,higher levels of NPAR,MLR,NLR and serum IL-17A were risk factors for poor prognosis,and the combined detection of the four indicators could effectively improve the predictive value for prognosis in patients with severe AE.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

Objective:To explore the impact of plant and animal dietary behaviors on type 2 diabetes mellitus (T2DM) in older adults aged ≥65 in 18 longevity areas of China.Methods:The subjects were 5 223 older adults over 65 years old from the Healthy Ageing and Biomarkers Cohort Study (HABCS) in 18 longevity areas in China. Through a questionnaire survey and physical examination, information about their demographic characteristics, lifestyles, daily activities, self-health status, current diseases, and fasting venous blood were collected. Food Frequency and Questionnaire (FFQ) was used to collect data on food intake frequency. Based on the prior method, the plant-based diet index (PDI) and animal-based diet index (ADI) of 5 223 older adults were calculated. Subjects were divided into three groups (low-level group: PDI<39 or ADI<31, middle-level group: 39≤PDI≤42 or 31≤ADI≤34, high-level group: PDI>42 or ADI>34) by tertiles of PDI and ADI. Multivariate logistic regression was used to analyze the association between PDI and ADI and the risk of T2DM.Results:The average age of 5 223 subjects was (84.8±11.5) years, with the median ( Q1, Q3) of PDI about 41(38, 43) and the median ( Q1, Q3) of ADI about 33 (30, 35). The prevalence rate of T2DM was 16.41% (857/5 223). After adjusting for covariates, multivariate logistic regression showed that PDI was negatively associated with T2DM. Compared with the low-level group, the OR (95% CI) for T2DM in the high-level group was 0.83 (0.69-0.99). ADI was positively associated with T2DM, and compared with the low-level group, the OR (95% CI) for T2DM in the high-level group was 1.28 (1.06-1.55). For every one-point increase in PDI and ADI, the risk of T2DM decreased by 2% and increased by 3%, respectively, with the OR (95% CI) of 0.98 (0.96-1.00) and 1.03 (1.01-1.06), respectively. Conclusion:In Chinese older adults ≥65 years in 18 longevity areas, higher adherence to the plant-based behavior may be negatively associated with the risk of T2DM, while higher adherence to the animal-based behavior may be positively associated with the risk of T2DM.

Aim To investigate the effects of Congrong San(CRS)on learning and memory ability,hippocam-pal neuronal injury,and ferroptosis in rats with Alzhei-mer's disease(AD)and to explore the related mecha-nisms.Methods AD rat models were established and divided into Sham,Model,CRS low-dose,CRS medium-dose,CRS high-dose,and memantine groups.After treatment,Morris water maze,HE and Nissl staining,transmission electron microscopy,immunofluorescence staining,Western blot,and kit assays were performed to assess learning and memory ability,hippocampal neuro-nal injury,ferroptosis-related indicatorsand glucose reg-ulated protein 78 ku(GRP78)-(proteinkinaseR-li-keERkinase)PERK-(activating transcription factor 4)ATF4 pathway protein expression.Results Com-pared with the model group,rats in the CRS medium-and high-dose groups and the memantine group showed significant improvement in learning and memory abili-ty,reduced hippocampal neuronal injury,increased number of Nissl bodies,and ameliorated endoplasmic reticulum swelling and mitochondrial damage.In addi-tion,the expressions of GRP78,p-PERK/PERK,and ATF4 were downregulated,while GPX4 expression was upregulated in the CRS medium-and high-dose groups and the memantine group.Moreover,MDA content de-creased,and SOD and GSH-PX levels increased in these groups.Conclusions CRS can improve the learning and memory ability in AD rats,reduce hipp-ocampal neuronal injury and ferroptosis,and its mecha-nism may be related to the inhibition of the GRP78-PERK-ATF4 pathway,enhancement of GPX4 expres-sion,and reduction of oxidative stress levels,providing a new approach for the clinical treatment of AD.