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.Response to Comments on “Pretreatment 68Ga-PSMA-11 PET/CT to Predict the Response to Treatment With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma”
Shao-Hao CHEN ; Xiao-Hui WU ; Qian-Ren-Shun QIU ; Shao-Ming CHEN ; Jie ZANG ; Jun-Ming ZHU ; Cheng-Long ZENG ; Wei-Bing MIAO ; Xue-Yi XUE ; Ning XU
Korean Journal of Radiology 2026;27(2):188-190
3.Identification and in vitro validation of causative proteins in metabolic dysfunction-associated fatty liver disease: A study based on proteome-wide Mendelian randomization
Jianyi CHEN ; Wentao HUANG ; Yang LI ; Zewei ZHUO ; Qinming LI ; Yu LONG ; Weihong SHA ; Hao CHEN
Journal of Clinical Hepatology 2026;42(9):2067-2074
ObjectiveTo identify protein biomarkers and potential therapeutic targets associated with metabolic dysfunction-associated fatty liver disease (MAFLD) through an integrative multi-omics analysis. MethodsLarge-scale plasma protein quantitative trait locus data were integrated with MAFLD genome-wide association study data, and a proteome-wide Mendelian randomization analysis was performed. Summary data-based Mendelian Randomization (SMR)/heterogeneity in dependent instruments (HEIDI) test and colocalization analysis were used to assess significant proteins. The independent samples t-test was used for comparison of continuous data with homogeneity of variance between two groups, and the Welch-corrected t-test was used for comparison of continuous data with heterogeneity of variance. The transcriptomic validation results were compared with the Mendelian randomization results to evaluate the changing trends of gene expression, and boxplots were used to display the expression distribution of candidate genes between groups. ResultsAmong 7 130 proteins analyzed, 40 showed a causal relationship with MAFLD, among which 26 increased the risk of MAFLD and 14 exerted a protective effect against MAFLD (FDR<0.05). Nine proteins were supported by SMR/HEIDI (PSMR<0.05, PHEIDI>0.05), and 14 showed a strong colocalization signal (PPH4>0.9). The transcriptomic analysis identified 5 differentially expressed proteins (all P<0.05), i.e., adenosine diphosphate-ribosylation factor-like GTPase 2, insulin-like growth factor binding protein 2, casein kinase 1 delta (CSNK1D), leucine-rich repeat neuronal 1, and moesin (MSN). In vitro validation showed upregulated expression levels of MSN (1.612±0.346 vs 0.569±0.077, P<0.05), 14-3-3 protein theta (YWHAQ) (1.267±0.126 vs 0.313±0.029, P<0.05), and CSNK1D (0.871±0.025 vs 0.431±0.080, P<0.05) and a downregulated expression level of histone deacetylase 8 (0.637±0.059 vs 1.097±0.260, P<0.05) in the MAFLD cell model. Functional annotation showed that CSNK1D participated in circadian and metabolic regulation, YWHAQ modulated the Hippo pathway and lipid signal transduction, and MSN was associated with cytoskeletal remodeling and fibrogenic responses. ConclusionThe integrative proteogenomic analysis in this study shows that CSNK1D, YWHAQ, and MSN may be key mediators in the pathogenesis of MAFLD. These proteins have the potential to serve as novel biomarkers and therapeutic targets, providing new directions for research on disease mechanisms and the development of intervention strategies.
4.Mechanistic study on resveratrol alleviating renal injury in rats with uric acid nephropathy by inhibiting the PERK/eIF2α pathway
Yanhua CHEN ; Jibo ZHANG ; Li LONG ; Jianfeng YU ; Min XU ; Hao LIU
China Pharmacy 2026;37(20):2679-2684
OBJECTIVE To investigate the mechanism by which resveratrol improves renal injury in rats with uric acid nephropathy (UAN) through inhibition of the protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α) pathway.METHODS A UAN rat model was established via oral administration of adenine plus potassium oxonate, and the rats were divided into a UAN model group, a positive control group (allopurinol 10 mg/kg), a resveratrol group (100 mg/kg), and a resveratrol+tunicamycin group [resveratrol 100 mg/kg+tunicamycin (PERK activator) 1 mg/kg]. A control group (without modeling) was also established, with 6 rats in each group. Rats in each group were administered the corresponding drug solution and/or normal saline via gavage or intraperitoneal injection once daily for 28 consecutive days. The contents of renal function-related parameters (24-hour urinary total protein, and uric acid, creatinine and blood urea nitrogen in serum), the levels of inflammation-related markers [interleukin-6 (IL-6), IL-18, tumor necrosis factor-α (TNF-α), IL-10, and nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3)], and pathological changes in renal tissue were determined, and the score for tubular damage, the score for inflammatory infiltration, and the degree of mesangial proliferation were assessed. The mRNA expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), as well as the expressions of proteins associated with the PERK/eIF2α pathway, were measured in renal tissue from each group.RESULTS Compared with the control group, rats in the UAN model group exhibited marked tubular damage, inflammatory cell infiltration, and mesangial proliferation. The contents of renal function-related parameters, levels of IL-6, IL-18, TNF-α and NLRP3, scores for tubular damage and inflammatory infiltration, degree of mesangial proliferation, mRNA expressions of NGAL and KIM-1, and phosphorylation levels of PERK and eIF2α, as well as the expressions of activating transcription factor 4 and C/EBP homologous protein, were all significantly increased or upregulated, while IL-10 levels were significantly decreased ( P <0.05). Compared with the UAN model group, the resveratrol group and the positive control group showed significant improvements in all of the aforementioned parameters ( P <0.05). Tunicamycin could significantly reverse the beneficial effects of resveratrol on all quantitative parameters ( P <0.05).CONCLUSIONS Resveratrol can reduce inflammatory responses in renal tissue of UAN rats, and improve tubular damage and renal function. These effects may be related to the inhibition of endoplasmic reticulum stress mediated by the PERK/eIF2α pathway.
5.Discussion on Syndrome Differentiation and Treatment of Post-stroke Depression from the View of"Heart-Blood-Vessels"Integration
Chaoyi WANG ; Zijun HAO ; Xiangyu LONG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(5):1266-1271
Post-stroke depression(PSD)is one of the commonly-seen complications after stroke,which seriously affects patients'quality of life and outcome of disease.Traditional Chinese medicine(TCM)classifies PSD as the co-morbidity of stroke and depression.This paper explored the pathogenesis and therapeutic principles of PSD from the view of"heart-blood-vessels"integration.It is proposed that PSD originates from the lesions of blood and vessels,and then the heart-body is involved;the lesions of heart,blood and vessels can cause the disorders of spirit.The core pathogenesis is due to the deficiency of heart qi,unsmoothed circulation of the vessels,and blood stasis causing depression of spirit.The principle of intervention of PSD should be focused on protecting vessels and regulating blood,nourishing heart and tranquilizing.Protecting vessels can be achieved by generating vessels,soothing vessels,and unblocking vessels through the application of Shengmai San,Zhi Gancao Decoction,and Tongmai Sini Decoction respectively.Regulating blood can be achieved by activating blood and generating blood.For activating blood,Danshen Decoction and Xuefu Zhuyu Decoction can be employed;for generating blood,Bazhen Decoction,Renshen Yangrong Decoction and Danggui Buxue Decoction can be employed.For nourishing heart and tranquilizing,the modified Gan Mai Dazao Decoction and Guipi Decoction can be employed.The view of"heart-blood-vessels"integration makes up for the disadvantages in separating the physique from the spirit,and in separating the structure from the function in the theory of the vessels and collaterals,and expands the approach of TCM treatment for PSD.
6.Research progress on the application of intelligent medical treatment in abdominal war trauma
Si-Zhe WANG ; Xu SUN ; Ding-Chang LI ; Xian-Qiang LIU ; Wen-Xing GAO ; Wen ZHAO ; Hao LIU ; Guang-Long DONG
Medical Journal of Chinese People's Liberation Army 2025;50(1):22-27
Abdominal war trauma is a common and high-risk type of injury in the modern battlefield,with rapid changes in condition and a high mortality rate.There is an urgent need for emerging medical technologies to improve the efficiency and success rate of first aid for military casualties.With the development of artificial intelligence(AI),5G,and other emerging technologies,the concept of intelligent medical treatment is gradually forming and can assist in the diagnosis and treatment of abdominal trauma.This paper reviews the characteristics of abdominal war trauma in modern wars,discusses the application of intelligent medical treatment for abdominal war trauma and its drawbacks to be solved,aiming to provide reference for research related to abdominal war trauma.
7.Correlation analysis of single nucleotide polymorphisms of HLA gene with clinicopathological features and postoperative prognosis of primary hepatocellular carcinoma
Zheng-Long PAN ; Hao-Ming YIN ; Hao-Yan TANG ; Xiao-Fang LIU
Medical Journal of Chinese People's Liberation Army 2025;50(11):1390-1397
Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of human leukocyte antigen(HLA)genes and the clinicopathological features and postoperative prognosis of primary hepatocellular carcinoma(HCC).Methods A retrospective analysis was conducted on 328 patients with primary HCC who underwent surgery and had complete clinical data at Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College from January 2014 to September 2022.The genotypes of HLA-DRB1 rs2647073,rs3997872 and HLA-DQB1 rs1049055 loci were detected in all patients using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technology.Binary logistic regression was employed to examine the association between SNPs in the HLA gene and the clinicopathological features of primary HCC.Age,gender,drinking history,and HBV/HCV infection history were used as stratification factors for stratified analysis.Univariate Cox regression was used to analyze the correlation between HLA gene SNPs and postoperative prognosis,and the Kaplan-Meier survival curve of patients with primary HCC after surgery was drawn.Multivariate Cox regression was utilized to evaluate the independent risk factors affecting the postoperative prognosis of patients with primary HCC.Results Binary logistic regression analysis showed that rs2647073 CC genotype patients had a higher risk of tumor diameter≥5 cm than AA genotype patients(P=0.005).Patients with TT genotype of rs3997872 had a higher risk of vascular invasion than those with AA genotype(P=0.003).Stratified analysis showed that age≥60 years,history of HBV/HCV infection,female,male,no drinking history,and drinking history,HLA-DRB1 rs2647073 CC genotype had a higher risk of tumor diameter≥5 cm than AA+AC genotype(P<0.05).In patients≥60 years old,the TT genotype of HLA-DRB1 rs3997872 had a higher risk of vascular invasion than the AA+AT genotype(P<0.001).Moreover,regardless of whether the patients were male or female,with or without a drinking history,and with or without a history of HBV/HCV infection,patients with the TT genotype of HLA-DRB1 rs3997872 had a higher risk of vascular invasion than those with the AA+AT genotype(P<0.05).Patients with TT genotype of HLA-DRB1 rs3997872 had a poorer postoperative prognosis than those with the AT+AA genotype(P<0.001).HLA-DRB1 rs3997872 SNP(P=0.019),older age(P<0.001),history of HBV/HCV infection(P<0.001),capsular invasion(P=0.005),vascular invasion(P=0.018),advanced BCLC stage(P<0.001),non-radical surgery(P=0.024),and higher PS score(P=0.023)were independent risk factors for the postoperative prognosis of HCC patients.Conclusion The SNPs of rs2647073 and rs3997872 in HLA-DRB1 gene are associated with the clinicopathological features of primary HCC,and the SNP of rs3997872 is associated with the postoperative prognosis of patients with HCC.
8.Analysis of the effect of bladder artery embolization combined with sequential TURBt in the treatment of bladder cancer
Hao ZHENG ; Chengtao GU ; Hao XU ; Shaochen WANG ; Zilong ZHANG ; Long CHENG
Journal of Interventional Radiology 2025;34(12):1338-1342
Objective To evaluate the efficacy and safety of preoperative bladder artery embolization followed by transurethral resection of bladder tumor(TURBt)in treating bladder cancer.Methods A retrospective analysis was conducted on the clinical data of 129 bladder cancer patients treated at the Fourth Affiliated Hospital of Soochow University from January 2021 to June 2024.Exclusions included 2 cases of acute bleeding with shock,3 cases requiring staged surgery due to poor intraoperative visualization,7 cases with other malignancies,12 cases without TURBt performed within 24 hours after embolization,and 1 case where selective bladder artery embolization failed.Patients were divided into two groups based on whether they underwent pre-TURBt embolization.Group A(n=61)underwent TURBt alone,while Group B(n=43)underwent TURBt within 24 hours after bladder artery embolization.There were no statistically significant differences in gender composition,tumor size,or other clinical characteristics between the two groups(P>0.05).Statistical comparisons were made between the two groups regarding operation time,intraoperative blood loss,postoperative hospital stay,duration of postoperative catheterization,and incidence of adverse reactions.Results In Group A,the mean operation time was(67.9±14.2)min,intraoperative blood loss was(80.7±24.7)mL,postoperative hospital stay was(8.5±1.6)days,and catheterization duration was(6.9±1.1)days.In Group B,the mean operation time was(54.0±12.6)min,intraoperative blood loss was(58.6±27.3)mL,postoperative hospital stay was(7.3±1.4)days,and catheterization duration was(6.4±0.9)days.Operation time,intraoperative blood loss,postoperative hospital stay,and catheterization duration were significantly lower in Group B compared to Group A(P<0.05).There was no statistically significant difference in the incidence of postoperative adverse reactions between the two groups(P>0.05).Conclusion Preoperative bladder artery embolization followed by TURBt for bladder cancer reduces tumor blood supply,thereby decreasing intraoperative bleeding.This approach effectively minimizes surgical bleeding,shortens operation time and postoperative hospital stay,with minimal side effects.It represents a safe and effective combined treatment method worthy of clinical promotion and application.
9.Updates and amendments of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅰ)
Hao LI ; Mingrui SHEN ; Peng ZHANG ; Weimin ZHAI ; Long NI ; Bo HAO ; Yuxin ZHAO ; Yi HE ; Shuangcheng MA ; Rong SHU
Drug Standards of China 2025;26(1):17-22
The Chinese Pharmacopoeia is the legal technical standard which should be followed during the research,production,use,and administration of drugs.At present,the new edition of the Chinese Pharmacopoeia is planned to be promulgated and implemented.This article summarizes and analyzes the main characteristics and the content of updates and amendments of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅰ),to provide a reference for the correct understanding and accurate implementation the new edition of the pharmacopoeia.
10.The impact of adolescent mental health status on smartphone addiction and the construction of a predictive model
Zhiyuan LI ; Junlin WU ; Shuhan HE ; Menghan HAO ; Yujia WENG ; Congwen YANG ; Qianmei LONG ; Guoping HUANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(3):252-258
Objective:To explore the impact of adolescent mental health status on smartphone addiction, and construct a predictive model for smartphone addiction based on the eXtreme Gradient Boosting(XGBoost) algorithm and multivariate Logistic regression.Methods:In April 2023, a cross-sectional survey was conducted among 14 666 adolescents.All participants were systematically evaluated using a self-developed general information questionnaire, the middle school student mental health scale(MSSMHS), the adolescents self-harm scale(ASHS), the interaction anxiousness scale(IAS), the mobile phone addiction index(MPAI), the middle school students shame scale(MSSS), the UCLA loneliness scale(UCLA-LS), the multidimensional peer victimization scale(MPVS), and the basic psychological needs scale(BPNS).R software version 4.3.2 was used for data analysis. Participants were randomly divided into training set and validation set at the ratio of 7∶3.The XGBoost model and multivariate logistic regression model were constructed to predict the risk of smartphone addiction, and a nomogram was plotted.Model performance was evaluated using the Hosmer-Lemeshow test, area under the curve(AUC), and accuracy(ACC).Results:(1) A total of 14 036 high school students were included in the study, with 5 069(36.1%) exhibited smartphone addiction.The training set comprised 9 826 students, with 3 549(36.1%) being smartphone addicts.The validation set included 4 210 students, with 1 520(36.1%) being smartphone addicts.(2) The XGBoost model identified shame-proneness and social anxiety as the two main predictors of smartphone addiction.(3) Multivariate Logistic regression analysis revealed that anxiety( B=0.328, OR(95% CI)=1.39(1.07-1.81), P=0.015), interpersonal sensitivity( B=0.311, OR(95% CI)=1.36(1.05-1.77), P=0.018), learning pressure( B=0.606, OR(95% CI)=1.83(1.46-2.31), P<0.001), mood swings( B=0.775, OR(95% CI)=2.17(1.70-2.78), P<0.001), social anxiety( B=0.024, OR(95% CI)=1.02(1.01-1.04), P<0.001), shame-proneness( B=0.049, OR(95% CI)=1.05(1.04-1.06), P<0.001), and peer victimization( B=0.037, OR(95% CI)=1.04(1.02-1.06), P<0.001) were significant predictors of smartphone addiction.(4) The ACC and AUC values of the XGBoost model were 0.890 and 0.929 in the training set, and 0.865 and 0.864 in the validation set, respectively.The multivariate Logistic regression model achieved ACC and AUC values of 0.870 and 0.854 in the training set, and 0.867 and 0.859 in the validation set, respectively. Conclusion:Anxiety, interpersonal sensitivity, learning pressure, mood swings, social anxiety, shame-proneness, and peer victimization are identified risk predictors of smartphone addiction in high school adolescents.

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