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.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.