ObjectiveThis study aimed to construct a neural network model integrating readily available clinical data and two-dimensional （2D） conventional ultrasound images to evaluate the severity of steatotic liver disease （SLD）. MethodsClinical data and ultrasound images were retrospectively collected from 649 patients who underwent ultrasound attenuation imaging （ATI）. Using ATI as the reference standard， patients were divided into four groups： normal （S0）， mild （S1）， moderate （S2）， and severe （S3） SLD. Data were randomly divided into training and validation sets at an 8∶2 ratio. A contrastive language-image pre-training （CLIP） model was utilized to extract features from both clinical and imaging data， which were then used to train random forest （RF） and multilayer perceptron （MLP） models. The diagnostic performance of these multimodal models was compared their single-modal counterparts in the validation set. ResultsThe MLP model outperformed the RF model （AUC［95%CI］： S0 = 0.96 ［0.93-0.99］， S1 = 0.99 ［0.96-1.00］， S2 = 0.75 ［0.64-0.82］， S3 = 0.88 ［0.81-0.93］）. Furthermore， the multimodal fusion model demonstrated significantly superior performance compared to single-modal models （clinical data only： AUC［95%CI］ of 0.89 ［0.81-0.95］， 0.69 ［0.52-0.79］， 0.64 ［0.43-0.67］ and 0.80 ［0.73-0.90］ for S0-S3， respectively； image data only： AUC［95%CI］ of 0.91 ［0.86-0.96］， 0.89 ［0.67-0.89］， 0.69 ［0.58-0.78］ and 0.86 ［0.82-0.94］）. Metrics including precision， recall， F1-score， F2-score， confusion matrices， and loss function learning curves further confirmed that multimodal data fusion significantly improved the predictive capability. ConclusionThe proposed CLIP-based MLP multimodal model can effectively and automatically grade SLD severity. This demonstrates the significant advantage of integrating clinical and ultrasound data， providing an accurate and reliable adjunctive tool for the clinical management of chronic SLD.

Objective: To examine the association between health behaviors and depressive symptoms among junior and senior high school students, so as to provide evidence for combined behavioral interventions targeting adolescent mental health. Methods: From September to November 2023, a stratified cluster random sampling method was used to recruit 104 834 junior and senior high school students from all 13 prefecture level cities (124 districts/counties) in Heilongjiang Province, China. Multivariable Logistic regression models, as well as multiplicative and additive interaction analyses were employed to analyze the associations between health behaviors and depressive symptoms, and Chi-square tests for trend were conducted to explore ,the changing tendency in the risk of depressive symptoms with increasing numbers of health behaviors among junior and senior high school students. Results: Healthy diet ( OR =0.66, 95% CI =0.63-0.68), healthy physical activity ( OR =0.47, 95% CI =0.45-0.49), healthy outdoor activity ( OR =0.55, 95% CI =0.52-0.57), healthy sleep ( OR =0.72, 95% CI =0.69-0.75), and healthy screen use ( OR =0.79, 95% CI =0.76-0.82) were independently associated with lower rates of depressive symptoms (all P <0.01). The risk of depressive symptoms decreased progressively with an increasing cumulative number of health behaviors ( χ 2 trend =996.73, P <0.01). Except for the interaction between healthy diet and healthy sleep, significant additive interactions were observed among the remaining health behaviors( RERI =0.07-0.23,all P <0.05). The probability of depressive symptoms was lower among girls with 2-3 healthy behaviors than among boys ( Z =2.51, 2.65), lower among urban students with 2-3 healthy behaviors than among suburban county students ( Z =-2.36, -2.04), and lower among senior high school students with 2-4 healthy behaviors than among junior high school students ( Z =2.17, 2.10, 2.04) (all P <0.05). Conclusions Health behaviors are significantly associated with depressive symptoms among junior and senior high school students. The probability of depressive symptoms is lower among girls, urban students, and senior high school students who engage in multiple healthy behaviors. Implementing combined interventions targeting multiple health behaviors in these populations may yield greater benefits.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

Objective:To examine the impact of the"outpatient+inpatient"bundled integrated payment reform on the utilization of health services for patients with ordinary tuberculosis,and to evaluate its effectiveness in resource allocation and cost containment.Methods:Based on the Andersen model,clinical and health insurance data from a city in Hebei Province were analyzed.An empirical study was conducted on 5 656 patients using Ordinary Least Squares(OLS)regression and Propensity Score Matching(PSM)to assess outpatient and inpatient service utilization and related costs.Results:Patients in the post-reform group showed a significant increase in outpatient visits and outpatient costs(an average increase of approximately 4.809 visits and 266.368 yuan,respectively,P<0.001),while inpatient visits,inpatient costs,and total medical costs significantly decreased(reductions of approximately 0.302 visits,3 638.647 yuan,and 3 372.279 yuan,respectively,P<0.001).Conclusion:The bundled integrated payment model effectively promotes outpatient service utilization,optimizes inpatient resource allocation,and reduces medical costs.However,the sharp increase in outpatient workload may pose a risk of overutilization.Recommendations:Future initiatives should establish a dynamic monitoring and evaluation system that emphasizes both service quality and clinical outcomes in outpatient and inpatient settings.Furthermore,refining incentive and regulatory mechanisms is essential to ensure that cost control measures do not compromise medical quality and patient safety.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective Exploring the effect of Bian-stone-based herbal heat therapy on herbal heat ironing in gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients.Methods Convenience sampling method was used to select 68 cases of hematopoietic stem cell transplantation patients who attended the hematology department of a tertiary-level Chinese medicine hospital in Hangzhou from October 2023 to April 2024 as the study subjects,and the SPSS 26.0 statistical software was used to generate a random number for grouping into an experimental and a control group,with 34 cases in each group.On the basis of intravenous antiemetic medication and routine,the experimental group implemented the Bian-stone-based herbal heat therapy on the basis of intravenous antiemetic medication and conventional nursing care.In the control group,intravenous antiemetic drugs and routine care were used,and the intervention duration of both groups was 14 d,of which 7 d was a course of treatment,with a total of 2 courses of treatment.The incidence of gastroin-testinal reactions,Gastrointestinal Symptom Rating Scale(GSRS)score,Pepsin Ⅰ(PG Ⅰ),Pepsin Ⅱ(PG Ⅱ),and the ratio of PG Ⅰ to PG Ⅱ(PGR)before and after the intervention were compared between the 2 groups.Results The final sample of 66 cases was collected in this study,and 1 patient was dislodged from each of the control group and the experimental group.The comparison of the incidence of gastrointestinal reactions between the 2 groups within 14 days showed that the incidences of nausea,vomiting,abdominal distension,and diarrhea were lower in the experimental group than those in the control group(P＜0.05).GSRS scores on days 1,8,and 14 of intervention were compared,and there were effects between groups in both groups(F=5.338,P=0.017).The levels of PG Ⅰ,PG Ⅱ in the experimental group on day 8 of the intervention were lower than those in the control group.The levels of PGR was higher than that in the control group(all P＜0.05).The safety of the 2 groups after treatment was evaluated,and the results showed that no serious adverse events occurred in the 2 groups.Conclusion Bian-stone-based herbal heat therapy can improve gastrointestinal reactions and reduce the incidence of gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients,which provides clinical guidance for the application of Bian-stone-based herbal heat therapy by nursing staff in the future.

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry* ; Calcium Sulfate/chemistry* ; Glycyrrhiza/chemistry* ; Crystallization ; Particle Size ; Medicine, Chinese Traditional ; Rhizome/chemistry*

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*