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

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

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 formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

The construction of a methodological system for medical humanities is the inevitable path for medical humanities research towards maturity. In response to existing practical dilemmas in this field， such as the lack of disciplinary norms and the fragmentation of research methods， this paper systematically integrated the philosophical methodologies of phenomenology and hermeneutics from the theoretical dimensions of ontology and epistemology. Grounded in the disciplinary nature and characteristics of medical humanities， it also strived to construct a three-dimensional methodological system that included methodological principles， general research methods， and specific research techniques. It also emphasized returning to the pursuit of the essence of knowledge， advocating for “integrated methodology，” and flexibly selecting and organically integrating multiple research methods based on specific research questions. The aim was to provide researchers with a reference for method selection， enhance their methodological self-awareness， and offer essential theoretical support for establishing a research system with disciplinary autonomy.

BackgroundIndividuals with chronic multimorbidity exhibit a high prevalence of sleep disturbances， which impair their physical and psychological well-being and impede chronic disease management. Although sleep quality is closely influencing with psychological functioning， empirical evidence regarding the longitudinal trajectories of sleep quality and their influencing factors in this population remains insufficient. ObjectiveTo investigate the longitudinal trajectories of sleep quality and associated factors among patients with chronic multimorbidity from hospitalization through 6 months post-discharge， aiming to facilitate the early identification of high-risk individuals and the development of personalized sleep interventions. MethodsA total of 228 inpatients with chronic multimorbidity， primarily with cardiovascular and metabolic chronic conditions， were enrolled via random sampling at The Third People's Hospital of Fuyang from January 2023 to September 2024. Baseline assessments were conducted during hospitalization using the general socio-demographic questionnaire， the Sleep Dysfunction Rating Scale （SDRS）， the Ruminative Response Scale （RRS）， and the Hospital Anxiety and Depression Scale （HADS）. Sleep quality was further evaluated using the SDRS at 1-， 3-， and 6-month post-discharge. Latent class growth model was employed to delineate trajectories of sleep quality. Multivariate logistic regression analysis was subsequently performed to identify influencing factors of sleep quality. ResultsA total of 201 patients with chronic diseases were included.Based on four predefined assessment time points （baseline， 1 month， 3 months， 6 months post-discharge）， the latent class growth model identified three distinct trajectories of sleep quality： persistent high sleep disturbance （n=72， 35.82%）， moderate sleep disturbance-progression （n=73， 36.32%）， and low sleep disturbance （n=56， 27.86%）. Multivariate logistic regression analysis revealed that， compared with the low sleep disturbance group， multiple factors increased the odds of membership in the persistent high sleep disturbance group： per capita monthly household income of <3 000 yuan （β=13.131， P<0.01） or 3 000–5 000 yuan （β=5.913， P<0.05）， aged 45–65 years （β=9.536， P<0.05）， presence of 3 （β=7.792， P<0.05） or >3 comorbid chronic conditions （β=6.626， P<0.05）， as well as higher RRS （β=0.334， P<0.01） and HADS score （β=1.628， P<0.01）. Additionally， patients aged 45–65 years （β=2.777， P<0.05）， with 3 （β=3.802， P<0.01） or >3 comorbid chronic conditions （β=2.463， P<0.01）， and with higher RRS （β=0.111， P<0.01） and HDAS scores （β=0.350， P<0.05） also demonstrated significantly increased odds of belonging to the moderate sleep disturbance–progression group. ConclusionThere is significant population heterogeneity in sleep quality trajectories among patients with chronic multimorbidity， with age， per capita household monthly income， number of comorbidities， rumination， and anxiety/depression symptoms being identify as the primary influencing factors.

Abstract Children s emotional and behavioral problems are characterized by a relatively high incidence, concealed manifestations, and a potential correlation with an increased risk of subsequent mental disorders. These problems have a sustained impact on children s social-emotional development, learning adaptation, and peer relationships. The study reviews the main influencing factors and their mechanisms of action regarding children s emotional and behavioral problems from three levels:individual, family, and social. Under a multi-level integrated perspective, it deepens the understanding of these mechanisms and proposes that future efforts should focus on factors such as improving physical fitness, enhancing sleep, and reducing sedentary behavior. Furthermore, it suggests strengthening collaborative interventions among schools, families, and communities to promote the early prevention of childrens emotional and behavioral problems and support their healthy development.

ObjectiveTo observe the clinical efficacy and safety of Tianmeng Lingjiao Formula（天礞羚角方， TLF） as an adjunctive therapy for paroxysmal atrial fibrillation （PAF） with phlegm-heat harassing the interior syndrome. MethodsNinety patients with PAF and phlegm-heat harassing the interior syndrome were enrolled and randomly assigned in a 2∶1 ratio to test group （60 cases） and control group （30 cases）. The control group received conventional western medicine， while the test group received TLF in addition to the conventional treatment， with one dose administered daily. The treatment course for both groups was 4 weeks. The efficacy of traditional Chinese medicine （TCM） syndrome and the rate of atrial fibrillation （AF） conversion were compared between groups. Assessments included AF burden， frequency and duration of AF episodes， TCM syndrome scores， and European Heart Rhythm Association （EHRA） AF symptom classification before and after treatment. Safety indicators such as blood routine， urine routine， stool routine， liver function， kidney function， and electrolytes were also monitored. Adverse events were recorded. ResultsA total of 82 patients completed the study （54 in the test group and 28 in the control group）. After treatment， AF burden， the frequency and duration of AF episodes， and TCM syndrome scores were significantly reduced in both groups， and the test group showed lower indicators than the control group （P＜0.01 or P＜0.05）. The AF conversion rate was 25.93% （14/54） in the test group， significantly higher than 3.57% （1/28） in the control group （P＜0.05）. The total effective rate for TCM syndrome efficacy was 83.33% （45/54） in the test group， which was significantly higher than 67.86% （19/28） in the control group （P＜0.05）. After treatment， the EHRA atrial fibrillation symptom severity in the test group showed significant improvement， and the improvement in atrial fibrillation symptoms was superior to that in the control group （P＜0.01or P＜0.05）. No significant abnormalities were observed in safety indicators， and no adverse events occurred during the trial. ConclusionTLF as an adjunctive therapy can reduce AF burden， enhance the conversion rate of AF， decrease the frequency and duration of episodes， and improve clinical symptoms in patients with paroxysmal atrial fibrillation presenting with phlegm-heat harassing the interior syndrome， with a favorable safety profile.

Based on the holistic view of "spleen-vessels-heart-spirit" system， this article explores the pathogenesis and progression of atrial fibrillation. It is proposed that the onset of atrial fibrillation is due to failure of the spleen to transport and disharmony of blood vessels； phlegm and blood stasis obstructing the collaterals and damage to the heart structure are the basis of its pathogenesis； the unclear mind and disorder of body and spirit are the causes of its progression. Based on the characteristics of pathological changes in different stages of the disease， it is proposed that early treatment should focus on restoring the middle jiao， clearing and promoting blood vessels， using modified Yigong Powder （异功散）； during the progression of the disease， treatment should remove blood stasis and phlegm， nourish heart and protect the pulse， using self-prescribed modified Mengshi Tongmai Decoction （礞石通脉汤）； meanwhile， calming mind and stabilizing palpitations， and regulating spirit should be sequentially incorporated， with self-prescribed Jiazao Ningmai Decoction （甲枣宁脉汤） or Shenying Dingji Decoction （参英定悸汤） and modified as appropriate. Clinical treatment should focus on the whole disease course of atrial fibrillation， implementing stage-based treatments to enable early intervention and holistic regulation.