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: To explore the efficacy of a Thalassemia risk assessment software for the screening of thalassemia mutation carriers and distribution of thalassemia genotypes detected by screening. METHODS: A total of 6 040 individuals were evaluated at Leshan Maternal and Child Health Care Hospital between 2022 and 2024 using the commonly used clinical thalassemia risk assessment method and the thalassemia screening software, respectively, and the performance indicators of the two methods were compared and analyzed against the result of thalassemia gene testing. This study was approved by the Ethics Committee of our hospital (Ethics No.: LfyLL[2022]005). RESULTS: The high-risk rate by the thalassemia screening software was 11.19%, with a sensitivity of 95.12%, specificity of 93.28%, positive predictive value of 43.20%, negative predictive value of 99.72%, and the area under the ROC curve (AUC) was 0.942. The thalassemia gene detection rate of the high-risk samples screened was 4.83%. The high-risk screening rate of the conventional method was 2.50%, with a sensitivity of 51.22%, specificity of 93.28%, positive predictive value of 80.79%, negative predictive value of 97.40%, and the AUC was 0.754. The thalassemia gene detection rate of the high-risk samples was 2.02%. CONCLUSION The software can effectively detect thalassemia carriers and significantly reduce the missed detection compared with conventional method, thereby significantly improve the efficacy of screening.
Humans ; Thalassemia/diagnosis* ; Software ; Female ; Genetic Testing/methods* ; Male ; Mutation ; Adult ; Genotype ; ROC Curve ; Risk Assessment

Objective: To systematically compare the types and contents of volatile organic compounds (VOCs) in purplish-brown and yellow-brown Ziziphi Spinosae Semen, and to provide a scientific basis for their rapid identification and quality evaluation.
Methods: Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was employed to determine the VOCs in two colored samples. GC-IMS spectra and fingerprint profiles were established, and chemometric methods including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to visualize the differences in volatile components.
Results: A total of 44 VOCs were identified, including 1 aldehyde, 9 esters, 10 ketones, 2 enals, 14 alcohols, 3 acids, 2 furans, 1 disulfide, and 2 hydrocarbons. Alcohols and esters were the main volatile components. The fingerprint profiles showed high consistency within groups but significant differences between groups. Both PCA and PLS-DA effectively distinguished the two sample types. Compounds such as pentanol, methyl butyrate, 2-ethylfuran, 2-hexanol, and 2-methylpropenal were identified as key markers for differentiation.
Conclusion: HS-GC-IMS combined with chemometrics accurately distinguishes the volatile compounds of Ziziphi Spinosae Semen with different colors. This method is rapid, sensitive, and suitable for quality control and rapid authentication of Ziziphi Spinosae Semen.

BACKGROUND:Impaired postural control is an important risk factor for falls and secondary damage in patients with idiopathic normal pressure hydrocephalus.Most of the existing studies have analyzed the gait parameters of patients during straight-line walking,but few have analyzed the postural stability characteristics of patients during static and dynamic activities. OBJECTIVE:To analyze the characteristics of postural stability in elderly patients with idiopathic normal pressure hydrocephalus. METHODS:Twenty-two patients clinically diagnosed with idiopathic normal pressure hydrocephalus at the Department of Neurosurgery,Huadong Hospital Affiliated to Fudan University,Shanghai,China,from September 2022 to February 2023 were selected as the patient group,and 18 healthy accompanying family members were selected as the healthy control group.The postural stability characteristics of the subjects were assessed using the Timed Up-and-Go Test,Multi-Directional Reach Test,Berg Balance Scale,and Static Balance Function Test(reaction time,speed of movement,directional control,maximum offset distance,and endpoint travel). RESULTS AND CONCLUSION:The time required to complete the Timed Up-and-Go Test was significantly longer in the patient group than in the healthy control group(P＜0.05).The results of the stretching test in the four directions of anterior,posterior,leftand right were significantly lower in the patient group than in the healthy control group(P＜0.05).The Berg Balance Scale scores in the patient group were lower than those in the healthy control group(P＜0.05).In the Static Balance Function Test,the results of reaction,movement speed,directional control,maximum offset distance and endpoint travel index were smaller in the patient group than the healthy control group(P＜0.05).To conclude,patients with idiopathic normal pressure hydrocephalus exhibit overall postural control deficits,and impaired reaction and execution abilities make these patients unable to make timely and accurate motor responses in the face of disturbances from internal or external sources,resulting in postural instability and increasing the risk of falls.

Background Fine particulate matter (PM_2.5) monitoring stations may generate missing data for a certain period of time due to various factors. This data loss will adversely affect air quality assessment and pollution control decision-making. Objective To propose an inverse distance weighted (IDW) spatiotemporal interpolation method based on particle swarm optimization (PSO) to interpolate and fill missing PM_2.5 spatiotemporal sequence data and increase interpolation accuracy. Methods An interpolation experiment was designed into two parts. The first part used hourly PM_2.5 observational data from four moments on January 1, 2017 in the Yangtze River Delta region. The second part employed daily PM_2.5 observational data from the first 10 d of January 2017 in the Beijing-Tianjin-Hebei region. Interpolation accuracy was evaluated using four metrics: root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and mean relative error (MRE). Results IDW spatiotemporal interpolation method optimized with PSO significantly improved the accuracy of filling missing PM_2.5 spatiotemporal sequence data. In the hourly-scale experiment conducted in the Yangtze River Delta region, compared to a distance index of 2, the accuracy metrics RMSE, MAE, MAPE, and MRE generated by the proposed method improved on average by 0.17 μg·m⁻³, 0.27 μg·m⁻³, 0.17%, and 0.01%, respectively. The PM_2.5 spatial field maps generated for four moments based on this method clearly illustrated the spatiotemporal distribution characteristics of hourly PM_2.5 concentrations in the Yangtze River Delta region. In the daily-scale experiment conducted in the Beijing-Tianjin-Hebei region, the PSO-optimized distance index outperformed the traditional method, with interpolation accuracy improvements of approximately 0.215 μg·m⁻³, 0.283 μg·m⁻³, 0.174%, and 0.014%, respectively. Furthermore, the seasonal PM_2.5 spatial field maps generated by this method revealed the spatiotemporal distribution characteristics of PM_2.5 concentrations in the Beijing-Tianjin-Hebei region across different seasons, further validating the effectiveness and applicability of this method. Conclusion The IDW spatiotemporal interpolation method optimized with PSO is highly accurate and reliable for interpolating the missing data in the Yangtze River Delta region and the Beijing-Tianjin-Hebei region, providing valuable insights for air pollution control and public health protection.

This paper summarizes Li Fei's academic insights and clinical experience in treating intractable facial paralysis.Li Fei posits that prolonged illness inevitably leads to deficiency and stasis,and thus,the treatment of intractable facial paralysis should first focus on identifying the etiology and syndrome differentiation,resolving stasis and unblocking stagnation,and regulating qi and blood,with particular emphasis on the relaxation of the meridian sinew system.The meridian sinew system,affiliated with the meridian and collateral,serves as the framework through which qi and blood nourish muscles,tendons,and joints,playing a crucial role in facial paralysis treatment.Guided by the theory of the meridian sinew system,Li Fei employs syndrome-based treatment,integrating the anatomy of facial expression muscles.His approach includes needle-knife therapy to release adhesions and break stasis,acupuncture to harmonize qi and blood,and intradermal needle therapy for sustained stimulation.Through these methods,the meridian sinew system is relaxed,qi and blood are regulated,and facial muscles are nourished,leading to gradual recovery from facial paralysis.

Objective To study the compliance and influencing factors of inhalation therapy in patients with stable chronic obstructive pulmonary disease (COPD),and carry out patient education and management accordingly. Methods COPD patients were selected from respiratory clinic of Luodian Hospital of Baoshan District of Shanghai from June to December in 2021. Compliance and inhalation techniques were assessed with the Morisky Medication Adherence Scale and the ten-step inhalation technique, and the factors influencing compliance were analyzed. Results A total of 58 outpatients with COPD were included, in which 25 cases (43.1%) with moderate or above compliance. Univariate analysis showed that the patients with course of disease ≥5 years, COPD assessment test(CAT)≥10 points, used 2 inhalation devices and inhalation technique score ≥8 points had better compliance when compared with other patients (P<0.05). Conclusion Patient education and management should be carried out actively. The patients with course of disease<5 years, CAT<10 points should be highly concerned. The inhalation devices should be chosen according to the patients' condition. Training on the use of devices should be strengthened and regularly follow-up evaluation should be carried out.

OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

This review systematically summarizes the unique metabolic mechanisms of breast cancer,their interac-tions with the tumor microenvironment(TME),and the latest advances in targeted therapies.The interplay between metabolic reprogramming and the TME underpins malignant progression and therapeutic resistance.Breast cancer cells reshape energy supply through the Warburg effect,aberrant fatty acid synthesis,and amino acid metabolism,while immune cells,fibroblasts,and the acidic milieu within the TME promote immune evasion and drug resistance via metabolic coupling.Although traditional strategies targeting key metabolic enzymes remain valuable,they are often insufficient to overcome metabolic adaptability.In recent years,combined metabolic and immunotherapeutic approaches have emerged as promising strategies:by reducing lactate accumulation,restoring T-cell function,and reprogramming tumor-associated macrophages and cancer-associated fibroblasts,these therapies can remodel the immunosuppressive microenvironment and enhance immunotherapy efficacy.The application of metabolomics and single-cell sequencing further elucidates breast cancer heterogeneity,providing a basis for individualized precision treatment.Future challenges include deciphering resistance mechanisms,developing highly selective metabolic in-hibitors,and designing integrated multi-omics-based therapeutic regimens.