ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate （ATP） binding cassette transporter G2 （ABCG2） expression in hyperuricemic （HUA） rats， and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley （SD） rats were randomized into a normal group， a model group， low-dose （282.6 mg·kg^-1） and high-dose （565.2 mg·kg^-1） Simiaowan groups， and a Benzbromarone （4.7 mg·kg^-1） group. The HUA model was established via intraperitoneal injection of potassium oxonate （ip） combined with oral gavage of hypoxanthine （ig） for 14 days. Following modeling， treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin （HE） staining， and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay （ELISA） quantified tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， diamine oxidase （DAO）， and D-lactic acid （D-LA） levels. Real-time polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry assessed the expression of Claudin-1， Occludin， occludens-1 （ZO-1）， and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group， the model group exhibited epithelial shedding in the ileal villus， structural disruption， infiltration of extensive inflammatory cells， and significantly elevated Chiu's scores （P<0.01）. The DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum were markedly increased （P<0.01）， while mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion， were significantly reduced （P<0.01）. Compared with the model group， the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus， significantly lowered Chiu's scores （P<0.01）， significantly reduced DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum （P<0.01）， and upregulated mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion （P<0.01）. The 16S rDNA results showed that in the model group， the α-diversity index of the ileal microbiota was increased， and species diversity and richness were enhanced， with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased， and the abundance of pathogenic bacteria was increased， with butyrate-producing bacteria showing a low abundance. In contrast， Simiaowan at all doses reduced species diversity and richness， regulated microbiota dysfunction， and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria， decreased the abundance of harmful bacteria， and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.

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.

This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation*

Diminished ovarian reserve (DOR) is a decrease in the number of available follicles in the ovaries and the quality of oocytes, which in turn affects follicle development, ovulation and sex hormone secretion, resulting in decreased fertility. Harmful chemical components in cigarette smoke, such as nicotine and benzopyrene, can interfere with the hypothalamic-pituitary-ovarian axis and impair ovarian reserve and function through apoptosis, autophagy, oxidative stress and DNA damage, which can directly affect ovarian granulosa cells and oocytes, causing oocyte development disorders, increased apoptosis of granulosa cells, destroy reproductive endocrine homeostasis, lead to DOR and affect female fertility. At present, the molecular mechanism of premature ovarian dysfunction caused by cigarette smoke is not fully understood. In this paper, the molecular mechanism of cigarette smoke exposure affecting ovarian tissue and mediating ovarian function was reviewed, aiming to provide theoretical reference for the study of cigarette smoke induced DOR and affecting ovarian function, and to provide pregnant guidance for infertile women in bad environment and bad living habits.

Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective:To investigate the clinical efficacy of robotic surgery via the bilateral axillo-breast approach（BABA） in lateral lymph node dissection for papillary thyroid carcinoma（PTC）. Methods:Clinicopathological records of 324 PTC patients receiving unilateral neck dissection in Tianjin Medical University Cancer Institute and Hospital from December 2020 to November 2024 were retrospectively analyzed. Of these patients, 108 underwent robotic surgery via BABA（robotic group）, while the remaining patients underwent conventional open surgery（open group）. The extent of lateral neck lymph node dissection included level Ⅱ, Ⅲ and Ⅳ. The differences in surgical indexes, postoperative complication rates and cosmetic outcomes of incisions were compared between two groups. Results:All study subjects completed the operation successfully, and there was no conversion in the robotic group. The average age of patients in the robotic group was lower than that in the open group, and the proportion of female patients was higher in the robotic group compared to the open group（P<0.05）. Patients in the robotic group had a greater number of dissected lymph nodes in level ⅡB and higher cosmetic scores（P<0.05）. There were no statistically significant differences between the two groups in the average dissection time of lateral cervical lymph nodes, the number of dissected lymph nodes and metastatic lymph nodes in level ⅡA, Ⅲ, and Ⅳ, average postoperative drainage volume, average postoperative hospital stay, and postoperative complication rates（P>0.05）. Conclusion:The application of robotic surgical system via BABA in lateral neck lymph node dissection for PTC is safe and feasible, with superior advantages in level ⅡB dissection and better postoperative cosmetic outcomes.
Humans ; Thyroid Neoplasms/surgery* ; Robotic Surgical Procedures/methods* ; Female ; Retrospective Studies ; Neck Dissection/methods* ; Lymph Node Excision/methods* ; Male ; Thyroid Cancer, Papillary ; Axilla/surgery* ; Thyroidectomy/methods* ; Breast/surgery* ; Middle Aged ; Adult ; Lymph Nodes/surgery* ; Treatment Outcome