ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Background Indoor air quality directly affects people's health, especially the impact of chemical pollutants in residential indoor air on children and the elderly is more significant. Objective To understand the pollution status of common chemical pollutants in residential indoor air in Shijiazhuang, evaluate the health risks of chemical pollutants to school-age children and the elderly, and provide reference for controlling indoor pollution in residential environment. Methods Using stratified random sampling, a total of 60 households were selected from 2 urban areas and 1 surrounding rural area in Shijiazhuang City, specifically in July 2023 (non-heating season) and December 2023 (heating season), respectively. Relevant data was collected through on-site sampling [including CO, CO₂, PM₁₀, PM_2.5, NO₂, SO₂, O₃, ammonia, formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), trichloroethylene, and tetrachloroethylene] and survey questionnaires. The pollutant concentrations were evaluated following the Standards for indoor air quality of GB/T 18883-2022, and the inhalation exposure risks of the target population were assessed based on the health risk assessment method. Results In the indoor air of the urban and rural residence in Shijiazhuang City, except for CO, NO₂, SO₂, toluene, and xylene, which did not exceed the standard limits, other pollutants showed varying degrees of exceedance. The non-qualified rates of PM₁₀, PM_2.5, and CO₂ in the urban areas were higher than those in the rural areas (P < 0.05). The seasonal difference analysis showed that the non-qualified rates of PM_2.5, PM₁₀, CO₂, trichloroethylene, and tetrachloroethylene in the urban areas were higher in the heating season than in the non-heating season (P<0.05); the non-qualified rates of ammonia and formaldehyde in the rural areas increased significantly in the non-heating season(P<0.05). The health risk assessment indicated that the maximum hazard quotient (HQ) of tetrachloroethylene for the elderly exceeded 1, while the HQ values for ammonia, formaldehyde, benzene, toluene, xylene, and trichloroethylene remained below 1 for either children or the elderly. For carcinogenic risks, the median carcinogenic risk (CR) of formaldehyde for school-aged children or the elderly fell within the range of 10⁻⁶-10⁻⁴, whereas the median CR values for benzene, trichloroethylene, and tetrachloroethylene were all below 10⁻⁶. Conclusion The primary indoor air pollutants exceeding the national standard limits in residential areas of Shijiazhuang City include CO₂, PM₁₀, TVOC, PM_2.5, formaldehyde, ammonia, trichloroethylene, and tetrachloroethylene. The levels of these pollutants exhibit significant urban-rural and seasonal variations. Special attention should be paid to the non-carcinogenic risk of tetrachloroethylene to the elderly and the carcinogenic risks of formaldehyde to school-age children and the elderly.

Objective: To understand the current situation and influencing factors of comorbidity of depressive and anxiety symptoms among middle school students in Chongqing, so as to provide a scientific basis for formulating a comprehensive strategy for the co prevention of multiple diseases among middle school students. Methods: From September to December 2024, 12 327 middle school students were selected from 6 districts and counties in Chongqing by the combination of stratified cluster sampling and convenience sampling method. The current status of depressive and anxiety symptoms was investigated by using the Center for Epidemiological Survey-Depression Scale (CES-D) and the Generalized Anxiety Disorder-7 (GAD-7). The Chi-squared test was used to compare the differences between groups with comorbidity of depressive and anxiety symptoms, multivariate Logistic regression analysis was used to analyze its related factors, and a nomogram prediction model was drawn. Results: The detection rates of depressive symptoms, anxiety symptoms and comorbidity among middle school students in Chongqing were 26.34%, 34.55% and 21.16%, respectively. Among them, the detection rates of the three types of symptoms in girls (29.80%, 40.99%, 25.15%) were all higher than those in boys (23.22%, 28.73%, 17.55%) ( χ 2=68.61, 204.23, 106.51, all P <0.01). Statistical significance was observed in the distribution of depressive and anxious symptoms among middle school students across different gender, academic stage, school district, family type, physical activity levels, parental discipline, smoking, alcohol consumption, sleep deprivation, excessive screen time, Internet addiction, and bullying ( χ 2=14.49-991.46, all P <0.01). Multivariate Logistic regression analysis showed that compared with junior high school students, ordinary high school students had a higher risk of comorbidity ( OR=2.71, 95% CI = 2.41-3.05); girls ( OR=2.17, 95%CI =1.95-2.40), non-core family ( OR=1.20, 95%CI =1.08-1.32), and good neighborhood ( OR=1.16, 95%CI =1.02-1.30), campus bullying ( OR=4.88, 95%CI =4.32-5.50), Internet addiction ( OR=4.77, 95%CI = 3.41 -6.68), parental beating and scolding ( OR=3.18, 95%CI =2.72-3.71), alcohol consumption ( OR=2.10, 95%CI =1.86- 2.37 ), and insufficient sleep ( OR=1.73, 95%CI =1.54-1.95) had higher risks with comorbidity of depression and anxiety symptoms (all P <0.05). A nomogram prediction model was constructed based on significant variables shows that C-index=0.75 (AUC= 0.75 , 95% CI=0.74-0.76, P <0.05), and the model had good predictive performance. Conclusions The current situation of comorbidity of depressive and anxiety symptoms among middle school students in Chongqing is not optimistic. The nomograms can be used to effectively predict the risk of comorbidity of depressive and anxiety symptoms in middle school students.

OBJECTIVE: Evaluate the clinical application effect of low-field infant MRI. METHODS: Using literature review, expert consultation, and two rounds of Delphi to determine the evaluation index system. Then retrospectively analyze and compare the data of low-field infant MRI and high-field MRI from January 2023 to December 2024. RESULTS: There is a certain gap between low-field infant MRI and high-field MRI in terms of signal-to-noise ratio, image uniformity, software system reliability, scanning time, user interface friendliness and image result consistency. However, there was no difference in terms of spatial resolution and image quality. The noise, hardware system reliability, mean time between failure and the rate of examination completed without sedation are better than that of high-field MRI. CONCLUSION Low-field infant MRI meets needs of clinical diagnostic and has stable performance. It can be used as a routine screening tool for brain diseases near the bed.
Magnetic Resonance Imaging/methods* ; Humans ; Infant ; Retrospective Studies ; Signal-To-Noise Ratio ; Reproducibility of Results ; Brain Diseases/diagnostic imaging* ; Brain/diagnostic imaging* ; Software

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Background::Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies. However, comprehensive reports on the burden of digestive system diseases in China are lacking. Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces.Methods::This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence, mortality rate, disability-adjusted life years (DALYs), years of life disability, years of life lost, and changes in the burden of digestive diseases across Chinese provinces from 1990 to 2019. The analysis of disease burden primarily examines the characteristics of sub-disease distribution, time trends, age distribution, and sex distribution. Additionally, we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index (SDI).Results::In 2019, there were 499.2 million cases of digestive system diseases in China, resulting in 1,557,310 deaths. Stomach cancer, colon and rectal cancer, and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases. Meanwhile, cirrhosis and other chronic liver diseases, gastroesophageal reflux disease, and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases. The risk of gastric cancer sharply increases among men after the age of 40 years, leading to a significant disparity in burden between men and women. As the SDI increased, the DALYs associated with digestive system diseases in China and its provinces showed a downward trend.Conclusion::Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI.