OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

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.

Objective To detect the isocenter of a medical linear accelerator using an optical surface monitoring system (OSMS) combined with a self-made 3D-printed phantom, and compare with the conventional front pointer measurement method. Methods A phantom that could be fixed to the front pointer of the accelerator was fabricated using 3D printing technology. The front pointer method and OSMS were used to detect the rotation isocenter deviations of the accelerator. During the experiments, the collimator, gantry, and couch linear displacement readings were recorded at different angles. We also recorded the measurement time of different surveyors. Results Compared to the front pointer measurement method, the OSMS method showed lower standard deviations. The reductions in standard deviations showed statistical significance in the Lat direction for the collimator rotation isocenter as well as in the Lat and Vrt directions for the gantry rotation isocenter. The mean deviation of Mag values for the collimator rotation isocenter using the OSMS method was 0.50 mm, which was larger than the 0.42 mm using the front pointer method. However, the standard deviation was 0.06 using the OSMS method, which was smaller than the 0.18 using the front pointer method. The mean deviation and standard deviation of Sag values for the gantry rotation isocenter using the OSMS method were 1.03 mm and 0.12, respectively, which were both larger than 0.47 mm and 0.06 using the front pointer method. For the couch rotation isocenter, the mean deviation and standard deviation using the OSMS method were 0.32 mm and 0.04, respectively, which were both smaller than the 0.55 mm and 0.20 using the front pointer method. All surveyors spent less time in isocenter measurements using the OSMS method compared to the front pointer method. Conclusion Compared with the front pointer method, the OSMS method significantly reduces the standard deviation among surveyors, effectively reduces the influence of the angle deviation of the accelerator on the measurement results, reduces detection time, improves detection efficiency, and provides a powerful practical basis for the application of OSMS in detecting the mechanical accuracy of the linear accelerator.

Objective To describe the clinical characteristics and nutritional management status of hospitalized elderly patients with multimorbidity in a tertiary hospital's geriatric center in 2024, and to analyze the correlation between nutritional status and hospitalization outcomes, thereby providing a basis for optimizing nutritional management pathways for this population. Methods A retrospective study was conducted, including 2 937 elderly patients with multimorbidity. Data on general information, clinical indicators, nutritional risk screening and assessment, nutritional therapy, and costs were collected for descriptive analysis. The relationship between nutritional status (based on BMI and serum albumin levels) and hospitalization outcomes was explored. Results The average age of the patients was (77.45±10.70) years, with 57.17% being male. The average number of chronic diseases diagnosed was (11.56±5.08) per patient, and 26.01% were critically ill. The nutritional risk screening rate was 80.40%, with a screening positivity rate of 33.44%. The nutritional assessment rate was 31.63%, and the malnutrition prevalence was 23.08%. The low BMI group had the longest median hospital stay [15 (9.75, 22) days] and the highest hospitalization costs [15 057.2 (8 980.48, 28 160.46) CNY]. Serum albumin levels were negatively correlated with hospital stay duration (rs=-0.276, P< 0.01) and hospitalization costs (rs=-0.276, P<0.01). Conclusion Hospitalized elderly patients with multimorbidity are characterized by multiple comorbidities and high healthcare resource consumption. While the nutritional risk screening rate is relatively high, there remains room for improvement in nutritional assessment and therapy. It is necessary to strengthen standardized management throughout the entire process. Nutritional status is a significant variable affecting hospital stay duration and costs, with poorer nutritional status significantly associated with prolonged hospitalization and higher costs, suggesting that it may be an important factor influencing hospitalization outcomes.

Objective To detect the isocenter of a medical linear accelerator using an optical surface monitoring system (OSMS) combined with a self-made 3D-printed phantom, and compare with the conventional front pointer measurement method. Methods A phantom that could be fixed to the front pointer of the accelerator was fabricated using 3D printing technology. The front pointer method and OSMS were used to detect the rotation isocenter deviations of the accelerator. During the experiments, the collimator, gantry, and couch linear displacement readings were recorded at different angles. We also recorded the measurement time of different surveyors. Results Compared to the front pointer measurement method, the OSMS method showed lower standard deviations. The reductions in standard deviations showed statistical significance in the Lat direction for the collimator rotation isocenter as well as in the Lat and Vrt directions for the gantry rotation isocenter. The mean deviation of Mag values for the collimator rotation isocenter using the OSMS method was 0.50 mm, which was larger than the 0.42 mm using the front pointer method. However, the standard deviation was 0.06 using the OSMS method, which was smaller than the 0.18 using the front pointer method. The mean deviation and standard deviation of Sag values for the gantry rotation isocenter using the OSMS method were 1.03 mm and 0.12, respectively, which were both larger than 0.47 mm and 0.06 using the front pointer method. For the couch rotation isocenter, the mean deviation and standard deviation using the OSMS method were 0.32 mm and 0.04, respectively, which were both smaller than the 0.55 mm and 0.20 using the front pointer method. All surveyors spent less time in isocenter measurements using the OSMS method compared to the front pointer method. Conclusion Compared with the front pointer method, the OSMS method significantly reduces the standard deviation among surveyors, effectively reduces the influence of the angle deviation of the accelerator on the measurement results, reduces detection time, improves detection efficiency, and provides a powerful practical basis for the application of OSMS in detecting the mechanical accuracy of the linear accelerator.

Objective To detect the isocenter of a medical linear accelerator using an optical surface monitoring system (OSMS) combined with a self-made 3D-printed phantom, and compare with the conventional front pointer measurement method. Methods A phantom that could be fixed to the front pointer of the accelerator was fabricated using 3D printing technology. The front pointer method and OSMS were used to detect the rotation isocenter deviations of the accelerator. During the experiments, the collimator, gantry, and couch linear displacement readings were recorded at different angles. We also recorded the measurement time of different surveyors. Results Compared to the front pointer measurement method, the OSMS method showed lower standard deviations. The reductions in standard deviations showed statistical significance in the Lat direction for the collimator rotation isocenter as well as in the Lat and Vrt directions for the gantry rotation isocenter. The mean deviation of Mag values for the collimator rotation isocenter using the OSMS method was 0.50 mm, which was larger than the 0.42 mm using the front pointer method. However, the standard deviation was 0.06 using the OSMS method, which was smaller than the 0.18 using the front pointer method. The mean deviation and standard deviation of Sag values for the gantry rotation isocenter using the OSMS method were 1.03 mm and 0.12, respectively, which were both larger than 0.47 mm and 0.06 using the front pointer method. For the couch rotation isocenter, the mean deviation and standard deviation using the OSMS method were 0.32 mm and 0.04, respectively, which were both smaller than the 0.55 mm and 0.20 using the front pointer method. All surveyors spent less time in isocenter measurements using the OSMS method compared to the front pointer method. Conclusion Compared with the front pointer method, the OSMS method significantly reduces the standard deviation among surveyors, effectively reduces the influence of the angle deviation of the accelerator on the measurement results, reduces detection time, improves detection efficiency, and provides a powerful practical basis for the application of OSMS in detecting the mechanical accuracy of the linear accelerator.

In this study, the pharmacodynamic components and potential pharmacological functions of Danzhi Xiaoyao Formula in treating nervous system diseases were investigated by hippocampal component characterization and network pharmacology. After rats were administrated with Danzhi Xiaoyao Formula by gavage, high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) was employed to explore the components in the hippocampus of rats. Fifty-seven components were identified in the hippocampus of rats by comparing the extract of Danzhi Xiaoyao Formula, herbal components in the hippocampus after administration, and blank samples. KEGG and GO analyses predicted 74 core targets including GSK3B, MAPK1, AKT, IL6. These targets were involved in PI3K/Akt, NF-κB, MAPK, JAK/STAT, Wnt, and other signaling pathways. The results indicated that Danzhi Xiaoyao Formula may ameliorate other nervous system diseases enriched in DO, such as neurodegenerative diseases, cerebrovascular diseases, and mental and emotional disorders by mediating target pathways, inhibiting inflammation, reducing neuronal damage, and alleviating hippocampal atrophy. The relevant activities exhibited by this formula in nervous system diseases such as Alzheimer's disease, Parkinson's disease, and diabetic neuropathy have extremely high development value and are worthy of further in-depth research. This study provides a theoretical basis and practical guidance for expanding the application of Danzhi Xiaoyao Formula in the treatment of nervous system diseases.
Drugs, Chinese Herbal/administration & dosage* ; Animals ; Rats ; Hippocampus/metabolism* ; Network Pharmacology ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Rats, Sprague-Dawley ; Male ; Nervous System Diseases/genetics* ; Humans ; Signal Transduction/drug effects*

To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

Background: This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018. Methods: We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO. Results: The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups. Conclusion This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.