1.Primary Cilium-mediated Mechano-metabolic Coupling: Cross-system Homeostatic Regulation of The Nervous, Bone, Vascular, and Renal Systems
Liang-Chen DUAN ; Hao-Liang HU ; Shu-Zhi WANG ; Jia-Long YAN ; Lin-Xi CHEN
Progress in Biochemistry and Biophysics 2026;53(3):577-592
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.
2.Predictive Factors Associated With Dysphagia in Patients With Traumatic Brain Injury
Shu-Mei YANG ; Ting-Ju LAI ; Ya-Chu HSU ; Yu-Lin LU ; Hsing-Yu CHEN ; Hsiao-Ting TSAI ; Sheng-Hao CHENG ; Ming-Yen HSIAO ; Meng-Ting LIN
Annals of Rehabilitation Medicine 2026;50(2):117-128
Objective:
To identify early clinical predictors associated with dysphagia and delayed swallowing recovery in patients with traumatic brain injury (TBI).
Methods:
In this retrospective study, we enrolled adult TBI patients admitted to the rehabilitation unit of a tertiary medical center between June 2019 and June 2023. Data on baseline characteristics, neurological status, imaging findings, and rehabilitation-related variables were collected. Swallowing function was assessed using two indicators: (1) nasogastric (NG) tube retention and (2) the Functional Oral Intake Scale (FOIS) scores at 1, 4, and 12 weeks post-injury. Regression analyses were conducted to identify predictors associated with dysphagia and swallowing recovery.
Results:
A total of 160 patients were included. At 1 week post-injury, longer intensive care unit (ICU) stay, poor initial sitting balance and use of sedative medication in ICU were associated with NG tube retention. At 4 weeks, lower initial Rancho Los Amigos Scale (RLAS) scores, immobility-related complications, longer hospitalization, and temporal lobe hematomas were associated with persistent NG tube dependence. By 12 weeks, older age, delayed ability to follow commands, and poor initial sitting balance remained associated with NG tube retention. FOIS outcomes were also associated with older age, delayed time to follow commands, impaired initial sitting balance, prolonged ICU stay, temporal lobe hematomas, lower initial RLAS scores, immobility-related complications, prolonged endotracheal tube placement and extended hospital stays.
Conclusion
Impaired cognitive status, poor physical function, immobility-related complications, and temporal lobe hematomas were key factors associated with dysphagia and delayed oral intake in individuals with TBI.
3.Divergent Small Vessel Disease Burden in Warfarin-Associated and Direct Oral Anticoagulant-Associated Intracerebral Hemorrhage
Sung-Chun TANG ; Ya-Fang CHEN ; Chih-Hao CHEN ; Ching-Hua KUO ; Yuan-Chang CHAO ; Yu-Fong PENG ; Shu-Wen LIN ; Shin-Yi LIN ; Jiann-Shing JENG
Journal of Stroke 2026;28(2):334-338
4.Influence of atrial septal defect on mitral valve growth after repair of coarctation of the aorta or an interrupted aortic arch in infants
Yi-Chia WANG ; Heng-Wen CHOU ; Chi-Hsiang HUANG ; Hsing-Hao HUANG ; Yih-Sharng CHEN ; En-Ting WU ; Shyh-Jye CHEN ; Ming-Tai LIN ; Shuenn-Nan CHIU ; Shu-Chien HUANG
Clinical and Experimental Pediatrics 2026;69(4):322-329
Background:
Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair.
Methods:
We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied.
Results:
A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39).
Conclusion
Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.
5.Through The Lens of The Chest X-Ray: Revisiting Classical Signs of Pulmonary Embolism
Bing Chan SHU ; Caisha MOSES ; Jung Hao YUNG
Brunei International Medical Journal 2026;22():27-30
Pulmonary embolism (PE) may present with subtle but specific radiographic clues on chest X -ray. We describe a series of three patients with acute PE demonstrating classical findings, including the Palla’s sign, Hampton ’s hump, and Westermark ’s sign, across varied clinical settings. In all cases, these findings prompted early diagnostic consideration and were subsequently confirmed by computed tomography pulmonary angiography. Echocardiographic findings varied between cases and ranged from normal ventricular function to evidence of right -ventricular strain. This case series highlights the continued educational value of recognising classical chest X -ray signs of PE, particularly in supporting early clinical suspicion when definitive imaging is delayed or not immediately available
6.Through The Lens of The Chest X-Ray: Revisiting Classical Signs of Pulmonary Embolism
Bing Chan SHU ; Caisha MOSES ; Jung Hao YUNG
Brunei International Medical Journal 2026;22():27-30
Pulmonary embolism (PE) may present with subtle but specific radiographic clues on chest X -ray. We describe a series of three patients with acute PE demonstrating classical findings, including the Palla’s sign, Hampton ’s hump, and Westermark ’s sign, across varied clinical settings. In all cases, these findings prompted early diagnostic consideration and were subsequently confirmed by computed tomography pulmonary angiography. Echocardiographic findings varied between cases and ranged from normal ventricular function to evidence of right -ventricular strain. This case series highlights the continued educational value of recognising classical chest X -ray signs of PE, particularly in supporting early clinical suspicion when definitive imaging is delayed or not immediately available
7.Relationship between obesity-related indicators, lipid levels, and POAG and risk factor analysis
Hao WANG ; Peiyu ZHU ; Shu ZHANG
International Eye Science 2026;26(8):1423-1427
AIM: To analyze the relationship between obesity-related indicators, blood lipid levels and primary open angle glaucoma(POAG)and explore its risk factors. METHODS:Patients with POAG treated in the hospital from March 2022 to March 2024 were selected as the POAG group, and healthy people in the same period were selected as the non-POAG group. The obesity related indicators [body mass index(BMI), waist circumference, waist-to-hip ratio], blood lipid levels [serum total cholesterol(TC), triglyceride(TG), high-density lipoprotein(HDL-C), low-density lipoprotein(LDL-C)] and general clinical data of the two groups were compared. The binary Logistic regression analysis was used to analyze the risk factors affecting the occurrence of POAG, and the ROC curve was established to analyze the efficiency of various variables in predicting the occurrence of POAG.RESULTS:A total of 54 POAG patients and 54 non-POAG subjects were included. The POAG group had a mean age of 50.30±5.73 y(29 males, 25 females), and the non-POAG group had a mean age of 50.28±5.72 y(28 males, 26 females).The BMI, intraocular pressure, waist circumference, waist-to-hip ratio, and TG levels in the POAG group were higher than those in the non-POAG group, while the HDL-C level was lower than that in the non-POAG group(all P<0.001). High BMI, high waist circumference, high waist-to-hip ratio, and high TG were identified as risk factors for POAG(all P<0.05), whereas high HDL-C was a protective factor(P<0.05).The AUCs for BMI, waist circumference, waist-to-hip ratio, TG, HDL-C, and the combined prediction were 0.885, 0.873, 0.707, 0.777, 0.664, and 0.974, respectively; the sensitivities were 0.815, 0.833, 0.730, 0.637, 0.663, and 0.944, respectively; and the specificities were 0.852, 0.759, 0.711, 0.789, 0.752, and 0.889, respectively. These results indicate that the combined multi-index prediction had the best performance, with good sensitivity and specificity.CONCLUSION:Obesity-related indicators such as high BMI, high waist circumference, high waist-to-hip ratio, and dyslipidemia(high TG, low HDL-C)are associated risk factors for POAG. The combined multi-index prediction model including BMI, waist circumference, waist-to-hip ratio, TG, and HDL-C demonstrates the best performance in POAG risk assessment, with both high sensitivity and specificity, providing a scientific basis for early clinical screening and intervention.
8.Effect of Zhinao Capsules on Mild and Moderate Sleep Disorders in Alzheimer's Disease Patients with Syndrome of Spleen-kidney Deficiency and Combined Phlegm and Stasis
Hu XI ; Wenming YANG ; Wenting XIE ; Yue YANG ; Shu ZHAI ; Hao LI ; Yulong YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):171-180
ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized, double-blind, placebo, controlled clinical trial design was adopted, and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method, the patients were assigned into a treatment group and a control group (30 in each group, with 29 patients in the treatment group and 28 patients in the control group finally completing the trial). The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules, and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index (PSQI), smart bracelet sleep monitoring, epworth sleeping scale (ESS), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), and traditional Chinese medicine symptoms were scored. Furthermore, the brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA) levels were measured. ResultsAfter 12 weeks of treatment, the total response rate of clinical efficacy assessment in the treatment group reached 89.7%, which was significantly higher than that (21.4%) in the control group (Z=-5.14, P<0.01). After treatment, the TCM symptom scores declined in both groups (P<0.01), and the scores in the treatment group were lower than those in the control group (P<0.01). After treatment, the treatment group showed decreased total score and seven component scores of the PSQI scale (P<0.05, P<0.01), and the scores in the treatment group were lower than those in the control group (P<0.05, P<0.01). After treatment, the treatment group showed increases in the duration of deep sleep, light sleep, rapid eye movement sleep, and total sleep at night and decreases in the time to fall asleep, the number of awakenings from sleep at night, and the time for sporadic daytime naps (P<0.01). The control group did not show significant changes in the duration of light sleep, time to fall asleep, and number of awakenings from sleep at night. Moreover, the treatment group outperformed the control group in terms of the indicators above (P<0.05, P<0.01). After treatment, the treatment group showed decreased scores of ESS, ADL and its subscales physical self-maintenance scale (PSMS), and Instrumental Activities of daily living scale (IADLs) and increased score of MMSE and levels of BDNF and GABA (P<0.05, P<0.01). There was no significant difference in PSMS between the two groups, and the treatment group was significantly better than the control group in terms of the rest of the above indicators (P<0.05, P<0.01). Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI, ESS, and ADL scores, increase the MMSE score and the expression of BDNF and GABA, effectively optimize the structure of sleep, improve the intelligence, and enhance the ability of daily life, without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.
9.Effect of Zhinao Capsules on Mild and Moderate Sleep Disorders in Alzheimer's Disease Patients with Syndrome of Spleen-kidney Deficiency and Combined Phlegm and Stasis
Hu XI ; Wenming YANG ; Wenting XIE ; Yue YANG ; Shu ZHAI ; Hao LI ; Yulong YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):171-180
ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized, double-blind, placebo, controlled clinical trial design was adopted, and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method, the patients were assigned into a treatment group and a control group (30 in each group, with 29 patients in the treatment group and 28 patients in the control group finally completing the trial). The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules, and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index (PSQI), smart bracelet sleep monitoring, epworth sleeping scale (ESS), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), and traditional Chinese medicine symptoms were scored. Furthermore, the brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA) levels were measured. ResultsAfter 12 weeks of treatment, the total response rate of clinical efficacy assessment in the treatment group reached 89.7%, which was significantly higher than that (21.4%) in the control group (Z=-5.14, P<0.01). After treatment, the TCM symptom scores declined in both groups (P<0.01), and the scores in the treatment group were lower than those in the control group (P<0.01). After treatment, the treatment group showed decreased total score and seven component scores of the PSQI scale (P<0.05, P<0.01), and the scores in the treatment group were lower than those in the control group (P<0.05, P<0.01). After treatment, the treatment group showed increases in the duration of deep sleep, light sleep, rapid eye movement sleep, and total sleep at night and decreases in the time to fall asleep, the number of awakenings from sleep at night, and the time for sporadic daytime naps (P<0.01). The control group did not show significant changes in the duration of light sleep, time to fall asleep, and number of awakenings from sleep at night. Moreover, the treatment group outperformed the control group in terms of the indicators above (P<0.05, P<0.01). After treatment, the treatment group showed decreased scores of ESS, ADL and its subscales physical self-maintenance scale (PSMS), and Instrumental Activities of daily living scale (IADLs) and increased score of MMSE and levels of BDNF and GABA (P<0.05, P<0.01). There was no significant difference in PSMS between the two groups, and the treatment group was significantly better than the control group in terms of the rest of the above indicators (P<0.05, P<0.01). Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI, ESS, and ADL scores, increase the MMSE score and the expression of BDNF and GABA, effectively optimize the structure of sleep, improve the intelligence, and enhance the ability of daily life, without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.
10.Microscopic Mechanism of Chronic Liver Disease and Novel Thinking of Medicine Management Based on Theory of "Yang Transforming Qi While Yin Constituting Form-sweat Pore"
Yuying XU ; Changpu ZHAO ; Rongzhi LI ; Yu ZHANG ; Fei WANG ; Chenyuan HAO ; Guangjie SHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):244-255
The theory of "Yang transforming Qi while Yin constituting form" in the Huangdi's Internal Classic is derived from the application, transformation, movement, and balance of Tao. It is highly condensed, revealing the true meaning of Tao and guiding the changes and progress of all natural things, including diseases. Therefore, the appearance of various physical diseases is the manifestation of Yin-Yang Qi transformation. Sweat pore, formed by the Qi transformation of Yin and Yang, is the nourishing and regulating system. It serves as the hub and channel, assisting in the flow and transformation of Qi, facilitating the exchange of material, energy, and information with the outside world. With sweat pore as the hub and based on the macro-control and holistic thinking of "Yang transforming Qi while Yin constituting form", this paper explores the microscopic mechanisms underlying chronic liver disease. In combination with the roles of mitochondria, exosomes, and the ultraliver sieve structure in the formation and progression of chronic liver disease, this paper elucidates the close internal relationship between the disease's initial quality, symptom signs, and its physiological and pathological functions under the guidance of this theory. Modern studies have shown that autophagy, intestinal flora disorders, glucose and lipid metabolism disturbances, activation of inflammatory factors, ferroptosis, and other microscopic pathological mechanisms are involved in the occurrence and development of chronic liver disease. The common connotation of the Yin-Yang concept in traditional Chinese medicine (TCM) and the pathological mechanisms in modern medicine is deeply analyzed. The corresponding relevant microscopic mechanisms and the guiding role of the theory of "Yang transforming Qi while Yin constituting form-sweat pore" in the management of chronic liver disease are summarized. Wind medicine promotes growth and transformation through sweat pore. The combination of pungent and sweet medicines facilitates Yang and disperse Yin. The formulas, combining the characteristics of wind medicine and pungent and sweet medicines, fit the principle of "Yang transforming Qi while Yin constituting form-sweat pore". This paper combines both macro and micro perspectives to explain the scientific connotation and microscopic mechanisms of chronic liver disease based on the theory of "Yang transforming Qi while Yin constituting form-sweat pore", and explore the prevention and treatment of chronic liver disease through the principles, methods, prescriptions, and medicines featured by combination of pungent and sweet medicines, facilitating Yang, activating sweat pore, and dispersing Yin, providing new ideas and reference for the clinical treatment of chronic liver disease.


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