Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective:To observe the high-frequency ultrasound characteristics of the median nerve（MN）in patients with acromegaly，and to investigate the clinical value of multiparameter quantitative ultrasound for noninvasive assessment of carpal tunnel syndrome（CTS）in acromegalic patients.Methods:A total of 132 acromegalic patients due to pituitary growth hormone tumors in Huashan Hospital during July 2023 to September 2024 including initial patients and postoperative revisions were prospectivly collected. The patients were divided into no neurological symptoms group（ n=51）and clinical CTS group（ n=81）based on the Boston Carpal Tunnel Questionnaire. All patients underwent bilateral MN ultrasonography，the ultrasound parameters included the cross-sectional area（CSA）of MN at the entrance of carpal tunnel，the maximum CSA of MN in carpal tunnel，the maximum and minimum thickness of MN in carpal tunnel，CSA of MN at forearm 1/3，soft tissue thickness at the wrist，CSA of MN at elbow transverse stripe，blood flow signals within the MN at the carpal tunnel，ratio of the CSA（CSA of MN at the entrance of carpal tunnel/ CSA of MN at forearm 1/3），ratio of thickness（maximum / minimum thickness of MN in carpal tunnel）. Differences in general information，clinical indicators and ultrasound parameters were analyzed between the two groups. The diagnostic model was established with ultrasound parameters and clinical indicators using univariate and multivariate logistic analyses in a training cohort of 106 patients，to predict CTS within acromegaly. And ROC curve was used to evaluate the efficacy of the model in a test cohort of 26 patients with neurophysiological examination data. Results:Patients in clinical CTS group were older，with longer disease duration，higher levels of growth hormone 25-hydroxyvitamin D 3 and insulin-like growth factor-1 and were more likely to have impaired glucose tolerance relative to the no neurologic symptoms group（all P < 0.05）. Comparison between the two groups revealed significant differences in all ultrasound parameters：the CSA at the entrance of the MN carpal tunnel，the 1/3 of the forearm and the elbow were larger than the no neurological symptoms group（all P < 0.001），and the MN thickness ratio was greater observably in the clinical CTS group（ P < 0.001）. Greater thickness of the soft tissue at wrist and more blood flow signals in MN in carpal tunnel were revealed in clinical CTS group patients（ P < 0.001）.Combining the results of multifactorial logistic analysis，the multiparametric ultrasound combined with clinical index diagnosing model based on the predicted disease duration，CSA of MN at the entrance of carpal tunnel，MN thickness ratio and soft tissue thickness at the carpal tunnel was established to diagnose CTS combined with acromegaly. The ROC curve was plotted in the test cohort and the area under the curve for this model was 0.894. Conclusions:High-frequency ultrasound is sensitive to observe MN changes in acromegalic patients and the combination of multiparametric ultrasound and clinical index is useful for the non-invasive diagnosis of acromegalic patients with CTS.

OBJECTIVE: To construct a predictive model for the reduction in methadone maintenance treatment (MMT) and evaluate the effects of different interventions and other clinical factors on methadone reduction using Shapley additive explanations (SHAP). METHODS: Two clinical trials of acupuncture for methadone reduction in MMT patients were analyzed, and the baseline data, MMT related information, intervention measures, the data related to dose-reduction outcomes were collected. The predictive model was constructed by means of 6 machine learning algorithms including support vector machine (SVM), K-nearest neighbors (KNN), logistic regression (LR), Naive Bayes (NB), random forest (RF) and categorical-boosting (CatBoost), and 2 integration methods, blending-ensemble method (Blending) and Stacking-ensemble method (Stacking). SHAP was employed for the interpretability analysis of the optimal model. RESULTS: A total of 251 MMT patients were included, 128 cases in the acupuncture group and 123 cases in the non-acupuncture group. CatBoost and Stacking performed optimally in the test set. CatBoost obtained an accuracy of 0.780 0±0.060 8, a precision of 0.500 0±0.120 0, a recall of 0.818 2±0.140 2, F1 score of 0.620 7±0.114 0, and receiver operating characteristic-area under curve (ROC-AUC) of 0.857 8±0.140 2 for the subjects. In MMT patients with acupuncture as an adjunctive therapy, the top 5 important features for methadone reduction, included intervention measures, body mass index (BMI), the duration of MMT, the history of opioid use and occupation; and SHAP values were 1.25, 0.36, 0.21, 0.19 and 0.12, respectively. The SHAP feature dependence plot showed that BMI, MMT duration and the history of opioid use presented a nonlinear negative correlation with the reduction effect. CONCLUSION In acupuncture as adjunctive therapy for methadone reduction, the clinical factors should be considered comprehensively; and the interpretable predictive model provides a scientific basis for it, which is conducive to the improvement of clinical strategy of acupuncture for methadone reduction and the development of personalized reduction scheme.
Humans ; Methadone/therapeutic use* ; Acupuncture Therapy ; Adult ; Female ; Male ; Machine Learning ; Middle Aged ; Opiate Substitution Treatment ; Young Adult

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To observe the high-frequency ultrasound characteristics of the median nerve（MN）in patients with acromegaly，and to investigate the clinical value of multiparameter quantitative ultrasound for noninvasive assessment of carpal tunnel syndrome（CTS）in acromegalic patients.Methods:A total of 132 acromegalic patients due to pituitary growth hormone tumors in Huashan Hospital during July 2023 to September 2024 including initial patients and postoperative revisions were prospectivly collected. The patients were divided into no neurological symptoms group（ n=51）and clinical CTS group（ n=81）based on the Boston Carpal Tunnel Questionnaire. All patients underwent bilateral MN ultrasonography，the ultrasound parameters included the cross-sectional area（CSA）of MN at the entrance of carpal tunnel，the maximum CSA of MN in carpal tunnel，the maximum and minimum thickness of MN in carpal tunnel，CSA of MN at forearm 1/3，soft tissue thickness at the wrist，CSA of MN at elbow transverse stripe，blood flow signals within the MN at the carpal tunnel，ratio of the CSA（CSA of MN at the entrance of carpal tunnel/ CSA of MN at forearm 1/3），ratio of thickness（maximum / minimum thickness of MN in carpal tunnel）. Differences in general information，clinical indicators and ultrasound parameters were analyzed between the two groups. The diagnostic model was established with ultrasound parameters and clinical indicators using univariate and multivariate logistic analyses in a training cohort of 106 patients，to predict CTS within acromegaly. And ROC curve was used to evaluate the efficacy of the model in a test cohort of 26 patients with neurophysiological examination data. Results:Patients in clinical CTS group were older，with longer disease duration，higher levels of growth hormone 25-hydroxyvitamin D 3 and insulin-like growth factor-1 and were more likely to have impaired glucose tolerance relative to the no neurologic symptoms group（all P < 0.05）. Comparison between the two groups revealed significant differences in all ultrasound parameters：the CSA at the entrance of the MN carpal tunnel，the 1/3 of the forearm and the elbow were larger than the no neurological symptoms group（all P < 0.001），and the MN thickness ratio was greater observably in the clinical CTS group（ P < 0.001）. Greater thickness of the soft tissue at wrist and more blood flow signals in MN in carpal tunnel were revealed in clinical CTS group patients（ P < 0.001）.Combining the results of multifactorial logistic analysis，the multiparametric ultrasound combined with clinical index diagnosing model based on the predicted disease duration，CSA of MN at the entrance of carpal tunnel，MN thickness ratio and soft tissue thickness at the carpal tunnel was established to diagnose CTS combined with acromegaly. The ROC curve was plotted in the test cohort and the area under the curve for this model was 0.894. Conclusions:High-frequency ultrasound is sensitive to observe MN changes in acromegalic patients and the combination of multiparametric ultrasound and clinical index is useful for the non-invasive diagnosis of acromegalic patients with CTS.

Objective To systematically review current status and trends of alexithymia research and identify key research hotspots and frontiers in China through a visualised analysis,thereby to provide a reference for future studies.Methods The literature related to alexithymia in China from the establishment of CNKI and Web of Science core collection databases to July 7,2024 was searched,and the visual analysis was carried out through CiteSpace.Results The number of papers published in alexithymia in China showed a steady upward trend,and the publishing institutions were relatively concentrated,the cooperation between various institutions was less,and the research was relatively scattered.The research hotspots mainly focused on exploring the correlation and influencing factors between neurosis,mood disorders,mental health,personality characteristics,depression and alexithymia,etc.,and the current situation of elderly care and its correlation with alexithymia have become the current research hotspots.The key populations were mainly students,the elderly and teenagers.Conclusion The number and depth of papers published on alexithymia is on the rise of researchers.In the future,we should encourage and strengthen the cooperation and exchange of scholars and research institutions,and formulate evaluation plans and interventions based on the cultural characteristics of China,so as to form an accurate and standardized research system.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To systematically review current status and trends of alexithymia research and identify key research hotspots and frontiers in China through a visualised analysis,thereby to provide a reference for future studies.Methods The literature related to alexithymia in China from the establishment of CNKI and Web of Science core collection databases to July 7,2024 was searched,and the visual analysis was carried out through CiteSpace.Results The number of papers published in alexithymia in China showed a steady upward trend,and the publishing institutions were relatively concentrated,the cooperation between various institutions was less,and the research was relatively scattered.The research hotspots mainly focused on exploring the correlation and influencing factors between neurosis,mood disorders,mental health,personality characteristics,depression and alexithymia,etc.,and the current situation of elderly care and its correlation with alexithymia have become the current research hotspots.The key populations were mainly students,the elderly and teenagers.Conclusion The number and depth of papers published on alexithymia is on the rise of researchers.In the future,we should encourage and strengthen the cooperation and exchange of scholars and research institutions,and formulate evaluation plans and interventions based on the cultural characteristics of China,so as to form an accurate and standardized research system.

Objective:To investigate the value of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and texture analysis for predicting BRAF gene mutation in rectal cancer.Methods:The clinical diagnositic trial was conducted. The clinicopathological data of 36 rectal cancer patients who were admitted to the First People's Hospital of Shangqiu from January 2016 to June 2021 were collected. There were 28 males and 8 females, aged (50±4)years. All the 36 patients were confirmed by pathological examination. After genetic testing, 12 patients with BRAF mutant type of BRAF V600E mutation were allocated into the mutation group, and 24 patients with BRAF wild type were allocated into the non-mutation group. All patients underwent MRI scan before surgery, and IVIM related post-processing images were received by Function Tool post-processing software. Observation indicators: (1) consistency test between observers of IVIM para-meters and texture parameters; (2) comparison of IVIM parameters on MRI between the two groups; (3) comparison of texture parameters on MRI between the two groups; (4) diagnostic efficacy of IVIM and texture parameters. The intraclass correlation coefficient (ICC) was used to evaluate the consistency between observers, with ICC >0.80 as good consistency. The average values of para-meters with ICC >0.80 were included for further analysis. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed by the indepen-dent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Comparison of ordinal data was analyzed by the non-parameter rank sum test. The texture parameters were combined using the Logistic regression model. Receiver operating charac-teristic curve was used to analyze the predictive performance and calculate the sensitivity and specificity. Results:(1) Consistency test between observers of IVIM parameters and texture parameters: the ICCs between two observers of IVIM parameters including apparent diffusion coefficient, diffusion related coefficient, perfusion-related diffusion coefficient and perfusion-related parameter were 0.91, 0.90, 0.91, 0.89, respectively. The ICCs of texture parameters including the minimum value, the maximum value, the 10th percentile and the 25th percentile between two observers were <0.80 while the ICCs of texture parameters including mean value, the 50th percentile, the 75th percentile, the 90th percentile, energy, entropy, skewness and kurtosis between two observers were >0.80. (2) Comparison of IVIM parameters on MRI between the two groups: IVIM parameters of diffusion related coefficient and perfusion-related parameter on MRI were (0.70±0.13)×10 -3 mm 2/s and 0.39±0.30 for the mutation group, versus (0.79±0.12)×10 -3 mm 2/s and 0.17±0.10 for the non-mutation group, showing significant differences between the two groups ( t=-2.17, 2.46, P<0.05). (3) Comparison of texture parameters on MRI between the two groups: the texture parameters of mean value and energy on diffusion related coefficient image were 0.54±0.23 and 0.00(0.00,0.01) for the mutation group, versus 0.77±0.34 and 0.01(0.00,0.01) for the non-mutation group, showing significant differences between the two groups ( t=-2.12, Z=-1.35, P<0.05). (4) Diagnostic efficacy of IVIM and texture parameters: the areas under the curve (AUCs) of diffusion related coefficient, perfusion-related parameter, IVIM parameters combination, mean value of diffu-sion related coefficient image, energy value of diffusion related coefficient image, texture parameters combination were 0.69[95% confidence interval ( CI) as 0.52-0.84], 0.76(95% CI as 0.59-0.88), 0.79(95% CI as 0.62-0.91), 0.71(95% CI as 0.52-0.85), 0.79(95% CI as 0.62-0.91), 0.84(95% CI as 0.68-0.94), which were all lower than the AUC of IVIM and texture parameters combination as 0.92(95% CI as 0.79-0.99). Conclusions:IVIM parameters and texture parameters of MRI can non-invasively predict the mutation status of BRAF gene in rectal cancer. The combination of IVIM and texture parameters has a better predictive efficacy.