OBJECTIVE To observe the effects of Modified shaoyao gancao decoction on intestinal transit function， intestinal flora and the contents of metabolites [γ aminobutyric acid （GABA） and 5-hydroxytryptamine （5-HT）] in slow transit constipation （STC） rats. METHODS SD rats were randomly divided into blank group （10 rats） and modeling group （30 rats）， with half male and half female. The STC model was established by intragastric administration of Compound diphenoxylate tablets in the modeling group. The successfully modeled rats were randomly divided into model group， Modified shaoyao gancao decoction group [56 g/（kg·d）， calculated by crude drug] and positive control group [lactulose 2.09 g/（kg·d）]， with 10 rats in each group. Each administration group was given relevant medicine intragastrically， the blank group and model group received an equivalent volume of normal saline， once a day， for 14 consecutive days. During the experiment， the general situation of rats was observed in each group. After the last medication， the body weight was measured， and the Bristol score was used to evaluate the fecal characteristics. The fecal moisture content， intestinal propulsion rate， and the contents of GABA and 5-HT in intestinal content were detected； the diversity of intestinal flora in intestinal contents was investigated， and the correlation between the contents of GABA， 5-HT and relative abundance of microbiota was analyzed. RESULTS Compared with the model group， general conditions such as small body shape， sparse and rough fur， and slow movement were all improved in Modified shaoyao gancao decoction body weight， Bristol score， fecal moisture content，intestinal propulsion rate， 5-HT content， Chao1 index and Shannon index were increased significantly， while GABA content and Simpson index were decreased significantly （P＜0.05）. The intestinal flora of rats in the Modified shaoyao gancao decoction group could be classified as the same as the blank group， but was far from the model group； the relative abundances of Desulfobacterota， Firmicutes and Bacteroidota in this group showed a tendency of pull back， but the differences were not statistically significant compared to model group （P＞0.05）. Desulfobacterota was an intergroup differential factor （P＜0.05）. The content of GABA was negatively correlated with the relative abundance of Bacteroidota， Cyanobacteria， Patescibacteria and Actinobacteriota （P＜0.05）. The content of 5-HT was positively correlated with the relative abundance of Campilobacterota （P＜0.05）. CONCLUSIONS Modified shaoyao gancao decoction can improve the fecal properties and intestinal motility of STC rats. Its mechanism may be related to improving intestinal flora and then affecting the contents of GABA and 5-HT in intestinal contents. In addition， the contents of GABA and 5-HT may be significantly correlated with the relative abundance of specific bacterial phyla such as Bacteroidota and Campilobacterota.

OBJECTIVE To observe the effects of Modified shaoyao gancao decoction on intestinal transit function， intestinal flora and the contents of metabolites [γ aminobutyric acid （GABA） and 5-hydroxytryptamine （5-HT）] in slow transit constipation （STC） rats. METHODS SD rats were randomly divided into blank group （10 rats） and modeling group （30 rats）， with half male and half female. The STC model was established by intragastric administration of Compound diphenoxylate tablets in the modeling group. The successfully modeled rats were randomly divided into model group， Modified shaoyao gancao decoction group [56 g/（kg·d）， calculated by crude drug] and positive control group [lactulose 2.09 g/（kg·d）]， with 10 rats in each group. Each administration group was given relevant medicine intragastrically， the blank group and model group received an equivalent volume of normal saline， once a day， for 14 consecutive days. During the experiment， the general situation of rats was observed in each group. After the last medication， the body weight was measured， and the Bristol score was used to evaluate the fecal characteristics. The fecal moisture content， intestinal propulsion rate， and the contents of GABA and 5-HT in intestinal content were detected； the diversity of intestinal flora in intestinal contents was investigated， and the correlation between the contents of GABA， 5-HT and relative abundance of microbiota was analyzed. RESULTS Compared with the model group， general conditions such as small body shape， sparse and rough fur， and slow movement were all improved in Modified shaoyao gancao decoction body weight， Bristol score， fecal moisture content，intestinal propulsion rate， 5-HT content， Chao1 index and Shannon index were increased significantly， while GABA content and Simpson index were decreased significantly （P＜0.05）. The intestinal flora of rats in the Modified shaoyao gancao decoction group could be classified as the same as the blank group， but was far from the model group； the relative abundances of Desulfobacterota， Firmicutes and Bacteroidota in this group showed a tendency of pull back， but the differences were not statistically significant compared to model group （P＞0.05）. Desulfobacterota was an intergroup differential factor （P＜0.05）. The content of GABA was negatively correlated with the relative abundance of Bacteroidota， Cyanobacteria， Patescibacteria and Actinobacteriota （P＜0.05）. The content of 5-HT was positively correlated with the relative abundance of Campilobacterota （P＜0.05）. CONCLUSIONS Modified shaoyao gancao decoction can improve the fecal properties and intestinal motility of STC rats. Its mechanism may be related to improving intestinal flora and then affecting the contents of GABA and 5-HT in intestinal contents. In addition， the contents of GABA and 5-HT may be significantly correlated with the relative abundance of specific bacterial phyla such as Bacteroidota and Campilobacterota.

BACKGROUND:Obesity negatively affects dynamic balance during walking,and crossing barriers is a more routine functional activity that requires more stability in controlling body posture. OBJECTIVE:To investigate the differences in dynamic stability between obese and average males,and to assess the balance ability of obese males using a relatively more challenging obstacle crossing. METHODS:A total of 24 male youths(12 each in the obese and normal groups)were recruited to complete the tests of walking on level ground and crossing obstacles of different heights(4 cm,11 cm,15 cm)in random order.Kinematic and dynamic data were collected using the Qualisys motion capture system and Kistler force stage.Statistical analysis was performed using two-factor(2 groups * 4 movement types)repeated measures analysis of variance. RESULTS AND CONCLUSION:The obese group had a lower step speed than the normal group(P<0.05),the proportion of the first single support period decreased and the proportion of the second double support period increased when crossing the 11 cm versus 15 cm hurdles(P<0.05).When walking on level ground,the margin of stability in the internal and external directions in the normal group was greater than that of the obese group(P<0.05).When crossing the 4 cm hurdles,the margin of stability in the obese group was less than that in the normal group(P<0.05).When crossing the 11 cm hurdles,there was no significant difference between the two groups in the anterior-posterior direction(P>0.05),while there was a significant difference in the internal-external direction(P<0.05).When crossing the 15 cm hurdles,the margin of stability in the obese group was lower than that in the normal group(P<0.05).Overall,obesity decreases the body's ability to control the body,reduces dynamic stability during crossing the barrier,and increases the risk of falls compared with the general population.In addition,compared with level ground walking,the decrease in the dynamic stability when crossing barriers is more significant in the obese group than the general population.

Objective: To examine the association of joint effect of overweight and obesity with dyslipidemia on left ventricular hypertrophy (LVH) in children, so as to provide scientific evidence for the prevention of early cardiovascular damage in children. Methods: Data were obtained from the second followup crosssectional survey of Huantai Childhood Cardiovascular Health Cohort study in 2021, comprising 1 047 children aged 10-15 years with complete information. Based on overweight and obesity status and dyslipidemia status, all participants were divided into four groups:normal weight with normal lipid levels, normal weight with dyslipidemia, overweight and obesity with normal lipid levels, and overweight and obesity with dyslipidemia. Left ventricular mass index (LVMI) levels and prevalence of LVH across four groups were compared. Multivariate Logistic regression model was used to examine the association of joint effect of overweight and obesity with dyslipidemia on LVH in children. Results: There were significant differences in LVMI levels [(28.66±7.10, 29.63±4.71,31.49±5.86,32.65±4.80)g/m2.7] and prevalence of LVH (4.28%, 12.50%, 22.74%, 31.30%) across four groups (F/χ2=50.76, 90.92, P<0.05). After adjustment for confounding variables such as gender,age,screen time,sleep duration,fruit and vegetable intake,carbonated beverage consumption,physical activity and elevated blood pressure, compared to children with both normal weight and normal lipid levels, the risk of LVH in children with dyslipidemia alone increased (OR=3.27, 95%CI=1.57-6.82，P<0.05). Children with overweight and obesity alone also had a significantly increased risk of LVH (OR=6.33, 95%CI=3.76-10.66), and the highest risk was observed in those with both overweight and obesity with dyslipidemia (OR=9.66, 95%CI=5.35-17.43) (P<0.05). Conclusions The joint effect of overweight and obesity with dyslipidemia is positively correlated with LVH in children. To prevent LVH in children, both overweight and obesity with dyslipidemia should be paid attention to.

Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8⁺ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8⁺ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8⁺ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

Animal experiments are widely used in biomedical research for safety assessment, toxicological analysis, efficacy evaluation, and mechanism exploration. In recent years, the ethical review system has become more stringent, and awareness of animal welfare has continuously increased. To promote more efficient and cost-effective drug research and development, the United States passed the Food and Drug Administration (FDA) Modernization Act 2.0 in September 2022, which removed the federal mandate requiring animal testing in preclinical drug research. In April 2025, the FDA further proposed to adopt a series of "new alternative methods" in the research and development of drugs such as monoclonal antibodies, which included artificial intelligence computing models, organoid toxicity tests, and 3D micro-physiological systems, thereby gradually phasing out traditional animal experiment models. Among these cutting-edge technologies, 3D bioprinting models are a significant alternative and complement to animal models, owing to their high biomimetic properties, reproducibility, and scalability. This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research. It starts by detailing the essential elements of 3D bioprinting, including the selection and functional design of biomaterials, along with an explanation of the principles and characteristics of various printing strategies, highlighting the advantages in constructing complex multicellular spatial structures, regulating microenvironments, and guiding cell fate. It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors, infectious diseases, and rare diseases, as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart. Additionally,the review examines the role of 3D bioprinting in tissue engineering, discussing its contributions to the construction of functional tissues such as bone, cartilage, skin, and blood vessels, as well as the latest progress in regeneration and replacement. Furthermore, this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression, drug mechanisms, precision medicine, drug development, and tissue regeneration, and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance. In conclusion, as a cutting-edge in vitro modeling and manufacturing technology, 3D bioprinting is gradually establishing a comprehensive application system covering disease modeling, drug screening, toxicity prediction, and tissue regeneration.

Animal experiments are widely used in biomedical research for safety assessment, toxicological analysis, efficacy evaluation, and mechanism exploration. In recent years, the ethical review system has become more stringent, and awareness of animal welfare has continuously increased. To promote more efficient and cost-effective drug research and development, the United States passed the Food and Drug Administration (FDA) Modernization Act 2.0 in September 2022, which removed the federal mandate requiring animal testing in preclinical drug research. In April 2025, the FDA further proposed to adopt a series of "new alternative methods" in the research and development of drugs such as monoclonal antibodies, which included artificial intelligence computing models, organoid toxicity tests, and 3D micro-physiological systems, thereby gradually phasing out traditional animal experiment models. Among these cutting-edge technologies, 3D bioprinting models are a significant alternative and complement to animal models, owing to their high biomimetic properties, reproducibility, and scalability. This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research. It starts by detailing the essential elements of 3D bioprinting, including the selection and functional design of biomaterials, along with an explanation of the principles and characteristics of various printing strategies, highlighting the advantages in constructing complex multicellular spatial structures, regulating microenvironments, and guiding cell fate. It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors, infectious diseases, and rare diseases, as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart. Additionally,the review examines the role of 3D bioprinting in tissue engineering, discussing its contributions to the construction of functional tissues such as bone, cartilage, skin, and blood vessels, as well as the latest progress in regeneration and replacement. Furthermore, this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression, drug mechanisms, precision medicine, drug development, and tissue regeneration, and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance. In conclusion, as a cutting-edge in vitro modeling and manufacturing technology, 3D bioprinting is gradually establishing a comprehensive application system covering disease modeling, drug screening, toxicity prediction, and tissue regeneration.

Objective To analyze the economic cost of self-monitoring of gestational diabetes mellitus, and provide a basis for measuring the economic burden of gestational diabetes mellitus, and to provide a reference for the formulation of intervention development and the adjustment of resource allocation. Methods The individual economic cost of self-monitoring for gestational diabetes mellitus was measured based on a decision tree model, and the total economic cost of self-monitoring for gestational diabetes mellitus in Beijing was estimated. The uncertainty of the model parameters was analyzed using one-way sensitivity analysis. Results The average individual economic cost of gestational diabetes self-monitoring was 1184 RMB, and the individual cost incurred by choosing different types of blood glucose meters ranged from 403 to 18 000 RMB. The average individual economic cost of finger-stick blood glucose monitoring was 606 RMB and the average individual economic cost of continuous glucose monitoring was 2 374 RMB. The total economic cost of gestational diabetes self-monitoring in Beijing was 23.818 0 million RMB, and the total economic cost incurred by choosing different types of blood glucose meters ranged from 0.292 5 to 9.027 9 million RMB. The proportion of the finger-stick blood glucose monitoring had the greatest impact on the robustness of the results. Conclusion Finger-stick blood glucose monitoring is still the dominant self-monitoring method and is less costly than continuous glucose monitoring. Self-monitoring of pregnant women with gestational diabetes mellitus incurs certain economic cost and causes an economic burden on society.

OBJECTIVE To explore the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation （STC） by regulating acid-sensitive ion channel 3 （ASIC3）/extracellular signal-regulated kinase （ERK） signaling pathway. METHODS SD rats were used to construct an STC model by gavage with compound diphenoxylate. The successfully modeled rats were randomly divided into model group， Shaoyao gancao decoction group （1.5 g/mL）， lactulose group （208.4 mg/mL， positive control）， and combined inhibition group （Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20 μg/kg）， with 12 rats in each group. Additionally， 12 healthy rats were selected as the blank group. They were given relevant medicine once a day and continuously intervened for 14 days. After intervention， the intestinal propulsion function and visceral sensitivity of the model rats were detected. The expression of ASIC3 in the colon tissue of rats was observed by immunohistochemical staining. mRNA expressions of ASIC3， ERK1 and ERK2 as well as protein expressions of ASIC3， ERK1/2 and phosphorylated ERK1/2 （p-ERK1/2） in colon tissue of rats were detected； the ultrastructural changes of the enteric nervous system （ENS） -interstitial cell of Cajal （ICC）-smooth muscle cell （SMC） network in the rat colon were observed under electron microscopy. RESULTS Compared with the model group， the intestinal propulsion rate of the Shaoyao gancao decoction group was significantly increased， while the visceral pain threshold was significantly decreased. The proportion of the positive area of ASIC3 in the colonic tissue was significantly increased. The relative mRNA expression levels of ERK1， ERK2， and ASIC3， as well as the relative protein expression levels of p-ERK1/2 and ASIC3， and the p-ERK1/2 to ERK1/2 in the colonic tissue， were all significantly increased （P＜0.05 or P＜0.01）. Additionally， there was marked repair of the morphological structure of ICC and SMC， with closer gap junctions observed. Compared with the Shaoyao gancao decoction group， the combined inhibition group exhibited a diminished improvement in intestinal motility of rats， with statistically significant differences in the levels of some indicators （P＜0.05 or P＜0.01）； the repairing of the morphological structure of ICC and SMC was notably attenuated. CONCLUSIONS Shaoyao gancao decoction can effectively improve the intestinal transmission function and promote intestinal repair in STC rats， and its mechanism may be related to regulating the balance of the ENS-ICC-SMC network mediated by the ASIC3/ERK signaling pathway， thus promoting intestinal motility and reducing visceral sensitivity.

Objective: To explore the bidirectional associations among body mass index Z scores (BMI Z scores) and weight stigma with depressive symptoms in adolescents, thereby providing evidence for targeted intervention strategies. Methods: A stratified cluster random sampling method was employed to select 18 301 adolescents aged 12-18 years from all 12 prefectures (103 counties) in the Inner Mongolia Autonomous Region, and two waves of longitudinal surveys were conducted in September 2023 (T1) and September 2024 (T2) among the adolescents. Weight stigma was assessed by using a self developed questionnaire, depressive symptom was measured with the Center for Epidemiologic Studies Depression Scale (CES-D), and BMI Z scores were calculated according to the World Health Organization standards. Pearson correlation analysis was used to examine associations among variables, and cross lagged panel models were constructed to investigate the dynamic bidirectional relationships among the three variables. Results: Adolescents BMI Z scores and weight stigma with depressive symptoms all exhibited autoregressive stability across the two time points (autoregressive paths, all P <0.01). Cross lagged model comparisons indicated that the bidirectional path model achieved the best fit ( χ 2=12.65, RMSEA =0.017, CFI =1.000; △ χ 2=193.39, P <0.01), supporting dynamic bidirectional associations among the three variables. After adjusting for gender, age, subjective social status and only child status, T1 BMI Z scores among adolescents positively predicted T2 weight stigma ( β =0.061), and T1 weight stigma positively predicted T2 depressive symptoms ( β =0.608); in the reverse direction, T1 depressive symptoms predicted T2 weight stigma ( β =0.003), and T1 weight stigma predicted T2 BMI Z scores ( β =0.081) (all P <0.01). Conclusions There is a bidirectional cross lagged relationship among adolescents BMI Z scores and weight stigma with depressive symptoms, suggesting that weight stigma may serve as a key psychological variable linking obesity and depressive symptoms. Greater attention should be paid to the potential threat of weight stigma to adolescents mental health, with intervention strategies expanded from a solely physiological focus to encompass psychosocial dimensions.