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.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Objective To study the effects of Jinshui Liujun decoction(JLD)on airway inflammation and interferon-γ(IFN-γ)/interleukin-4(IL-4)imbalance in asthma.Methods The ovalbumin(OVA)was used to replicate the asthmatic mouse by injection and nebulization inhalation.Asthmatic mice were randomly divided into model group,positive control group(1.0 mg·kg-1 dexamethasone)and experimental-L,-M,-H groups(4.1,8.2 and 16.4 g·kg-1 JLD).The blank group and the model group were given purified water by gavage for 2 consecutive weeks.The lung function[tidal volume(TV)and respiratory rate(RR)]of mice was measured by lung function test system after administering JLD by gavage.IFN-γ,IL-4 in bronchoalveolar lavage fluid(BALF)and their genes in lung tissue were determined through enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction respectively.Results The TV levels in blank group,model group,positive control group and experimental-L,-M,-H groups were(118.90±24.20),(87.10±13.36),(112.70±18.92),(105.20±15.24),(107.60±16.47)and(110.10±17.41)μL;RR levels were(126.60±17.57),(178.80±31.06),(133.00±19.45),(146.00±25.82),(141.30±24.78)and(137.00±22.81)bpm;IFN-γ levels were(110.95±9.26),(60.16±2.75),(98.09±8.21)、(79.58±6.49)、(88.16±7.58)and(97.26±7.23)pg·mL-1;IL-4 levels were(118.06±8.47)、(416.08±22.21)、(272.17±13.14)、(319.34±15.27)、(298.77±14.83)and(278.71±14.24)pg·mL-1;the IFN-γ mRNA levels were 2.70±0.08,1.00±0.00,2.65±0.06,1.89±0.04,2.24±0.05 and 2.58±0.06;IL-4 mRNA levels were 0.25±0.02,1.00±0.00,0.26±0.02,0.61±0.05,0.50±0.03 and 0.33±0.03,respectively.There were statistically significant differences between the above indicators of model group and blank group,and experimental-L,-M,-H groups and model group(P＜0.05,P＜0.01).Conclusion JLD has a certain antiasthmatic effect and one of mechanisms is to alleviate the IFN-γ/IL-4 immune imbalance and inhibit airway inflammation.

ObjectiveTo analyze the research status and trends in low-level occupational benzene exposure. Methods Articles on low-level occupational benzene exposure from Chinese and English journals from January 1st, 2000, to December 31th, 2022 were retrieved using the Web of Science and the China National Knowledge Infrastructure, and a bibliometric analysis was conducted. Results A total of 327 articles were included in the analysis, comprising 216 English articles and 111 Chinese articles. i) The number of articles published in English fluctuates greatly over the years, without a trend of continuous growth or decline. Authors from 359 research institutions in 45 countries and regions have published relevant English articles in 97 kinds of journals, involving 281 grants from 226 foundations. The top three countries in terms of articles amount were the United States, Italy, and China, with 81, 46, and 43 papers, respectively. The English articles mainly focused on mechanistic research at the genetic level, such as hematotoxicity, oxidative stress, and DNA damage. ii) The number of Chinese articles increased gradually after 2012, with the growth peak in 2017. Authors from 127 research institutions in 26 provinces, autonomous regions, and municipalities published Chinese articles in 51 kinds of journals, involving 154 grants from 78 foundations. Chinese articles tended to focus on benzene-induced hematotoxicity and occupational health damage. Conclusion Most studies on low-level occupational benzene exposure were conducted in China, the United States and Italy, focused on hematotoxicity. Monitoring international research topics and hotspots of the field has certain reference value for related research in China.

Objective To study the effects of Jinshui Liujun decoction(JLD)on airway inflammation and interferon-γ(IFN-γ)/interleukin-4(IL-4)imbalance in asthma.Methods The ovalbumin(OVA)was used to replicate the asthmatic mouse by injection and nebulization inhalation.Asthmatic mice were randomly divided into model group,positive control group(1.0 mg·kg-1 dexamethasone)and experimental-L,-M,-H groups(4.1,8.2 and 16.4 g·kg-1 JLD).The blank group and the model group were given purified water by gavage for 2 consecutive weeks.The lung function[tidal volume(TV)and respiratory rate(RR)]of mice was measured by lung function test system after administering JLD by gavage.IFN-γ,IL-4 in bronchoalveolar lavage fluid(BALF)and their genes in lung tissue were determined through enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction respectively.Results The TV levels in blank group,model group,positive control group and experimental-L,-M,-H groups were(118.90±24.20),(87.10±13.36),(112.70±18.92),(105.20±15.24),(107.60±16.47)and(110.10±17.41)μL;RR levels were(126.60±17.57),(178.80±31.06),(133.00±19.45),(146.00±25.82),(141.30±24.78)and(137.00±22.81)bpm;IFN-γ levels were(110.95±9.26),(60.16±2.75),(98.09±8.21)、(79.58±6.49)、(88.16±7.58)and(97.26±7.23)pg·mL-1;IL-4 levels were(118.06±8.47)、(416.08±22.21)、(272.17±13.14)、(319.34±15.27)、(298.77±14.83)and(278.71±14.24)pg·mL-1;the IFN-γ mRNA levels were 2.70±0.08,1.00±0.00,2.65±0.06,1.89±0.04,2.24±0.05 and 2.58±0.06;IL-4 mRNA levels were 0.25±0.02,1.00±0.00,0.26±0.02,0.61±0.05,0.50±0.03 and 0.33±0.03,respectively.There were statistically significant differences between the above indicators of model group and blank group,and experimental-L,-M,-H groups and model group(P＜0.05,P＜0.01).Conclusion JLD has a certain antiasthmatic effect and one of mechanisms is to alleviate the IFN-γ/IL-4 immune imbalance and inhibit airway inflammation.

Objective:To study the differential expressions of piRNAs in the seminal plasma of men and the role of piRNAs in spermatogenesis.Methods:We sequenced the seminal plasma samples collected from 187 male infertility patients and 58 normal healthy men,obtained differentially expressed piRNAs,and detected the relative expressions of piRNAs in different types of sperm by RT-qPCR to explore their significance in the diagnosis of male infertility.Using histopathology,RNA-protein pull-down and Western blot,we investigated the action mechanism of piRNAs in spermatogenesis in the mouse model.Results:RT-qPCR of the seminal plasma samples revealed a high expression of hsa_piR_000478 in teratozoospermia and ROC curve analysis showed an auxiliary signifi-cance of hsa_piR_000478 in the diagnosis of the disease(AUC=0.7549).Transfection of hsa_piR_000478 and its homologous se-quence piR_mmu_54800729 into the seminiferous tubules of the mouse model significantly decreased sperm motility,increased the per-centage of morphologically abnormal sperm and destroyed the testicular structure.Molecular biological experiments exhibited a close correlation between piRNAs and the energy metabolism-related pathway,which elevated the level of cell glycolysis and interfered with normal spermatogenesis.Conclusion:hsa_piR_000478 has an auxiliary significance in the diagnosis of male infertility,and piRNAs may interfere with spermatogenesis by affecting the glycolysis-related pathway in the spermatogenic microenvironment of the testis.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).