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.

BACKGROUND:Studies have shown that intradiscal injection of syringin solution can improve the structure and function of the intervertebral disc,prevent and slow down the process of intervertebral disc degeneration in rats.However,the biological half-life of syringin is short and it is difficult for it to continue to play a role in the intervertebral disc.Its bioavailability needs to be further improved.OBJECTIVE:To observe the effect of syringin-chitosan hydrogel on intervertebral disc degeneration in rats and the mechanism of syringin in the treatment of intervertebral disc degeneration.METHODS:(1)Cell experiment:Passages 2-5 rat nucleus pulposus cells were divided into four groups for treatment.The normal control group did not undergo any treatment.The degeneration group was added with interleukin-1β(to establish the intervertebral disc degeneration cell model).The drug group was added with interleukin-1β and syringing.The inhibitor group was added with interleukin-1β,syringing,and phosphatidylinositol 3-kinase(PI3K)inhibitor LY294002.After 24 hours of treatment,apoptosis,extracellular matrix,oxidative stress,and apoptosis-related proteins and PI3K/protein kinase B(AKT)signaling pathway proteins were detected respectively.(2)Animal experiment:Syringin-chitosan hydrogels were prepared,and the micromorphology and slow-release properties of the hydrogels were tested.Thirty SD rats were randomly divided into model control group,model intervention group,hydrogel group,syringin solution group,and syringin hydrogel group,with 6 rats in each group.The intervertebral disc degeneration model was established by the acupuncture method.Immediately after model establishment,the rats in model intervention group,hydrogel group,syringin solution group,and syringin hydrogel group were injected with PBS,chitosan hydrogel,syringin solution,and syringin-chitosan hydrogel,respectively.The samples were taken 8 weeks after modeling for histological detection.RESULTS AND CONCLUSION:(1)Cell experiment:Compared with the normal control group,apoptosis rate,reactive oxygen species level,and expression of BAX,cleaved caspase-9,cleaved caspase-3,and matrix metalloproteinase 13 protein were increased in the nucleus pulpocytes in the degeneration group(P＜0.05),and the expression levels of p-PI3K,p-AKT,BCL-2,and type Ⅱ collagen were decreased(P＜0.05).Superoxide dismutase activity decreased(P＜0.05).Compared with the degeneration group,apoptotic rate,reactive oxygen species level,and expression of BAX,cleaved caspase-9,cleaved caspase-3,and matrix metalloproteinase 13 protein were decreased in the syringin solution and syringin solution groups(P＜0.05),and expression levels of p-PI3K,p-AKT,BCL-2,and type Ⅱ collagen were increased(P＜0.05).Superoxide dismutase activity increased(P＜0.05).LY294002 could partially inhibit the effect of syringin.(2)Animal experiment:Syringin-chitosan hydrogel had a loose porous structure and good slow-release performance.Hematoxylin-eosin and safranin O-fast green staining showed that compared with the model control group and model intervention group,chitosan hydrogel,syringin solution and syringing-chitosan hydrogel could improve the intervertebral disc degeneration in different degrees,and the therapeutic effect of syringing-chitosan hydrogel was better than that of hydrogel and drug solution alone.(3)These findings indicate that syringin can regulate apoptosis of nucleus pulposus cells and extracellular matrix degradation induced by oxidative stress by activating PI3K/AKT signaling pathway,thus delaying disc degeneration.Compared with syringin injection alone,syringin loading in chitosan hydrogel can further delay the progression of intervertebral disc degeneration in rats.

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective:To investigate the effects of short-term olfactory training and visual stimulation on olfactory recognition function and quality of life in patients following functional endoscopic sinus surgery (FESS).Methods:A total of 80 patients who underwent FESS in the Department of Otorhinolaryngology Head and Neck Surgery at the Affiliated Hospital of Xuzhou Medical University between December 2023 and February 2024 were enrolled in this study. The cohort comprised 67 males and 13 females, aged from 17 to 75 years. Participants were randomly allocated to either a control group ( n=40) or an experimental group ( n=40). The participants in control group received routine postoperative management, including nasal irrigation, oral antibiotics and glucocorticoids, topical budesonide nasal spray, and hypertonic saline solution for 12 weeks. In addition to the standard care, the participants in experimental group underwent olfactory-visual stimulation training starting 24 hours postoperatively, lasting for 2 weeks. The olfactory identification test (OIT), visual analogue scale (VAS) for olfaction and Questionnaire of Olfactory Disorders of Life (QOD-QoL, hereafter referred to as QOD) were administered preoperatively. Follow-up assessments were performed 2 weeks and 3 months postoperatively, with the same tests repeated. Data were analyzed using SPSS 27.0 and GraphPad Prism 7 statistical software. Results:There was no significant difference in preoperative OIT, VAS, and QOD scores between the two groups. The olfactory recognition function of some patients was improved after removing the packing material 24 hours after FESS surgery. The OIT scores of 2 weeks post-surgery were significantly higher than preoperative values in both groups (the experimental group Z=-4.73, P<0.001; the control group Z=-4.73, P<0.001). Participants in both groups showed improvements in olfactory VAS and QOD scores (experimental group Z value was -2.88 and -5.45, P<0.01 and<0.001, respectively; the control group Z value was -4.42 and -5.50, respectively, both P<0.001). However, there was no significant difference in the VAS score between the two groups ( Z=-0.68, P=0.499). The paticipants in experimental group showed greater improvement in OIT and greater reduction in QOD scores compared to the control group ( Z=-2.19, P=0.029; Z=-2.99, P=0.003). There was no significant difference in the decrease of olfactory VAS between the two groups ( Z=-0.02, P=0.988). There were no statistically significant differences of all patients in VAS, OIT and QOD scores at 2 weeks and 3 months after surgery (experimental group Z value was -0.91, -0.90 and -1.43, respectively, all P>0.05; control group Z value was -1.21, -0.84 and -0.91, respectively, all P>0.05). At 3 months post-surgery, the OIT scores in the experimental group were higher, the QOD scores were lower than those in the control group ( Z=-2.89, P=0.004; Z=-2.87, P=0.004). Conclusion:Short-term olfactory-visual stimulation training in the early postoperative period of FESS significantly improves the olfactory recognition function and enhances the quality of life of patients.

Objective:To investigate the efficacy and safety of a combination of programmed death receptor 1 (PD-1) inhibitor and multi-target tyrosine kinase inhibitor anlotinib in second-line treatment of non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Using the random number table method, 118 NSCLC patients who were admitted to Shaanxi Provincial Cancer Hospital from June 2021 to June 2023 were randomly divided into the control group and the observation group, with 59 patients in each group. The observation group was treated with PD-1 inhibitor combined with anlotinib, while the control group was treated with PD-1 inhibitor. There were 36 males and 23 females in the observation group, with an age of (56±5) years; there were 34 males and 25 females in the control group, with an age of (56±5) years. There was no statistically significant difference in general clinicopathological data between the two groups (all P > 0.05). The short-term clinical efficacy [objective response rate (ORR) and disease control rate (DCR)], tumor-related factor levels [vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase (TIMP), and tumor necrosis factor β1 (TNF-β1)], inflammatory status [plasma fibrinogen-to-albumin ratio (FAR)], lung function [forced vital capacity (FVC) and peak expiratory flow (PEF)] before and after treatment, the European Organization for Research and Treatment on Cancer (EORTC) core questionnaire for quality of life assessment (QLQ-C30) score, and occurrence of adverse reactions were compared between two groups of patients. Results:The ORR and DCR of the observation group were 33.90% (20/59) and 69.49% (41/59), respectively; the ORR and DCR of the control group were 10.17% (6/59) and 44.07% (26/59), respectively; the comparison of ORR and DCR between the two groups showed statistically significant differences ( χ2 values were 9.67 and 7.77, both P < 0.05). There was no statistically significant difference in the levels of tumor-related factors between the observation group and the control group before treatment (all P > 0.05); after 4 cycles of treatment, the levels of VEGF and MMP-2 in the observation group were lower than those in the control group, while the levels of TIMP and TNF-β1 were higher than those in the control group, and the differences were statistically significant (all P < 0.001). The FAR of the observation group and the control group before treatment were (0.15±0.06) g/L and (0.16±0.06) g/L, respectively, with no statistically significant difference ( t = 0.90, P = 0.367); after 4 cycles of treatment, the FAR were (0.07±0.01) g/L and (0.11±0.04) g/L, respectively, with statistically significant difference ( t = 7.45, P < 0.001). Before treatment, there was no statistically significant difference in FVC and PEF between the observation group and the control group (both P > 0.05); after 4 cycles of treatment, the FVC and PEF in the observation group were higher than those in the control group, and the differences were statistically significant (both P < 0.001). There were no statistically significant differences in the EORTC QLQ-C30 scores of functional dimension, symptom dimension and global health status/quality of life dimension between the observation group and the control group before treatment (all P > 0.05); after 4 cycles of treatment, the scores of functional dimension and global health status/quality of life dimension in the observation group were higher than those in the control group, while the symptom dimension score was lower than that in the control group, and the differences were statistically significant (all P < 0.001). The incidence of adverse reactions in the observation group was 6.78% (4/59), while in the control group it was 10.17% (6/59), and the difference was not statistically significant ( P = 0.741). Conclusions:The combination of PD-1 inhibitor and anlotinib in second-line treatment of NSCLC has good clinical efficacy, it can reduce the inflammatory response, improve the lung function and quality of life, and has good safety.

Objective:To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province,and to analyze the genotypes and hematological phenotypes.Methods:Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province,whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations.The mutations of β-globin gene clusters were confirmed by polymerase chain reaction(PCR)and Sanger DNA sequencing technology.Results:The 3.5 kb deletion in β-globin gene cluster(NC_000011.10:g.5224302-5227791 del3490bp)was detected in 4 patients'samples,of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation.These 2 patients displayed moderate anemia phenotype,while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype.Conclusion:Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia,compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia.In areas with a high incidence of thalassemia,suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.

Mesenchymal stem cells(MSCs)play a crucial role in tissue repair and regeneration,and the extracellular vesicle(EV)released by them holds great promise for applications in clinical biomarkers,vaccines,and drug delivery.However,MSCs-derived EV(MSCs-EV)face challenges such as low pro-duction yield,poor retention,and targeted delivery issues.There-fore,engineering MSCs-EV to enhance their performance and en-able visual research has become a hot topic.Curcumin(CUR),an active component in traditional chinese medicine,exhibits pharmacological effects but has limited bioavailability.Using MSCs-EV as a carrier for CUR delivery can address its solubility and bioavailability challenges.This article reviews the drug loading methods,engineering strategies of MSCs-EV,and their important applications in the delivery and treatment of CUR for cartilage injury diseases.It provides a basis for the clinical ap-plication of engineered MSCs-EV in CUR delivery for cartilage repair,offering potential solutions to the challenges in cartilage tissue repair.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Objective To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in elderly hypertensive population. Methods Elderly physical examination population who received dual-energy bone mineral density examination and bone metabolic marker test in the hospital were selected from January 2021 to December 2024. According to whether they had hypertension and dual-energy bone mineral density results, the enrolled patients were divided into hypertension OP group (142 cases ), hypertension non-OP group (173 cases), non-hypertension OP group (102 cases) and non-hypertension non-OP group (100 cases). GNRI of all study subjects was measured. The correlation of GNRI and the occurrence of OP was explored by logistic regression analysis. The predictive efficiency of GNRI on the occurrence of OP was evaluated by receiver operating characteristic (ROC) curve. Results The BMD and GNRI in the hypertension group, and the non-hypertension OP group were significantly lower than those in the non-hypertension non-OP group (P<0.05). Compared with the hypertension non-OP group, the BMI, GNRI, BMD, and 25-OH Vit D in the hypertension OP group were significantly reduced (P<0.05) while the PTH level was significantly enhanced (P<0.05).logistic regression analysis showed that GNRI, 25-OH Vit D and PTH were closely related to OP in the elderly hypertensive population (P < 0.05). ROC curve analysis manifested that the AUC value of GNRI alone in predicting OP in elderly hypertensive population was 0.802, which was higher than that of 25-OH Vit D (AUC=0.723) and PTH (AUC=0.643). The AUC, sensitivity and specificity of combination of GNRI, 25-OH Vit D and PTH in predicting OP in elderly hypertensive population were 0.837, 66.20% and 86.13% (P<0.05). Conclusion GNRI is closely related to the occurrence of OP in elderly hypertensive population, and GNRI can be used as a potential indicator to assess the risk of OP.