Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.
Animals ; Humans ; Mice ; Lymphatic Metastasis/pathology* ; Disease Models, Animal ; Cell Line, Tumor

Objective: To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health. Methods: From 2024 to 2018, a total of 1 588 mother child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height for age Z score(HAZ), weight for age Z score(WAZ), weight for length/height Z score(WHZ), and head circumference for age Z score(HCAZ) at 1 and 3 years of age. Results: After adjusting for confounders, GEE analysis revealed that each natural log unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62 %, 5.04 %, and 8.33%, respectively, at 1 and 3 years of age (FDR- P <0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR- P <0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%). Conclusions Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the therapeutic effect and mechanisms of live combined bifidobacterium and lactobacillus tablets on slow transit constipation(STC)rats.Methods A total of 30 SPF grade Wistar adult female rats were blinded and divided into control group,model group,live combined bifidobacterium and lactobacillus tablets low-dose(0.270g/kg),live combined bifidobacterium and lactobacillus tablets medium dose group(0.540g/kg),live combined bifidobacterium and lactobacillus tablets high-dose group(1.080g/kg),and positive drug group(prucalopride succinate tablet)(0.180mg/kg),with 5 rats in each group.A rat model of STC was established by gavage of loperamide hydrochloride.After successful modeling,medication was administered by gavage for 14 consecutive days on the basis of continued modeling.Observe the changes in general physical signs,fecal water content,and calculate intestinal motility in each group of rats.Using HE staining to observe pathological changes in colon tissue,immunohistochemical methods were used to detect the protein expression of receptor tyrosine kinase(c-Kit),5-hydroxytryptamine(5-HT),5-hydroxytryptamine 3 receptor(5-HT3R),and 5-hydroxytryptamine 4 receptor(5-HT4R)in rat colon tissue.Results Compared with control group,frequency of defecation,fecal water content and intestinal propulsion speed of STC model rats were significantly decreased.The expression levels of proteins such as c-Kit,5-HT,5-HT3R,and 5-HT4R in intestinal tissues were significantly reduced in STC model rats.Compared with STC model group,rats treated with low,medium and high doses of live combined bifidobacterium and lactobacillus tablets and positive drug groups showed a significant increase in bowel frequency,fecal water content,and intestinal motility after intervention.Compared with STC model group,frequency of defecation,fecal water content,intestinal propulsion rate and protein expression of c-Kit,5-HT,5-HT3R and 5-HT4R in rat intestinal tissues were significantly increased after intervention of live combined bifidobacterium and lactobacillus tablets low,medium and high dose groups.Conclusion This study confirms that probiotic preparation live combined bifidobacterium and lactobacillus tablets effectively improves slow transit constipation by promoting the proliferation of Cajal interstitial cells in the colon,increasing the expression of 5-HT,5-HT3R,and 5-HT4R,enhancing intestinal peristalsis,and achieving the therapeutic effect on STC rats.

Objective To investigate the therapeutic effect and mechanisms of live combined bifidobacterium and lactobacillus tablets on slow transit constipation(STC)rats.Methods A total of 30 SPF grade Wistar adult female rats were blinded and divided into control group,model group,live combined bifidobacterium and lactobacillus tablets low-dose(0.270g/kg),live combined bifidobacterium and lactobacillus tablets medium dose group(0.540g/kg),live combined bifidobacterium and lactobacillus tablets high-dose group(1.080g/kg),and positive drug group(prucalopride succinate tablet)(0.180mg/kg),with 5 rats in each group.A rat model of STC was established by gavage of loperamide hydrochloride.After successful modeling,medication was administered by gavage for 14 consecutive days on the basis of continued modeling.Observe the changes in general physical signs,fecal water content,and calculate intestinal motility in each group of rats.Using HE staining to observe pathological changes in colon tissue,immunohistochemical methods were used to detect the protein expression of receptor tyrosine kinase(c-Kit),5-hydroxytryptamine(5-HT),5-hydroxytryptamine 3 receptor(5-HT3R),and 5-hydroxytryptamine 4 receptor(5-HT4R)in rat colon tissue.Results Compared with control group,frequency of defecation,fecal water content and intestinal propulsion speed of STC model rats were significantly decreased.The expression levels of proteins such as c-Kit,5-HT,5-HT3R,and 5-HT4R in intestinal tissues were significantly reduced in STC model rats.Compared with STC model group,rats treated with low,medium and high doses of live combined bifidobacterium and lactobacillus tablets and positive drug groups showed a significant increase in bowel frequency,fecal water content,and intestinal motility after intervention.Compared with STC model group,frequency of defecation,fecal water content,intestinal propulsion rate and protein expression of c-Kit,5-HT,5-HT3R and 5-HT4R in rat intestinal tissues were significantly increased after intervention of live combined bifidobacterium and lactobacillus tablets low,medium and high dose groups.Conclusion This study confirms that probiotic preparation live combined bifidobacterium and lactobacillus tablets effectively improves slow transit constipation by promoting the proliferation of Cajal interstitial cells in the colon,increasing the expression of 5-HT,5-HT3R,and 5-HT4R,enhancing intestinal peristalsis,and achieving the therapeutic effect on STC rats.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Diabetic kidney disease(DKD)is a common complication of diabetes mellitus and approximately 1/3 of diabetic patients may progress to DKD.A typical early clinical manifestation of DKD is microalbuminuria and patients may present with macroproteinuria accompanied by a decrease in renal function condition as the disease progresses.It is generally believed that the likelihood of a reversal of the disease is reduced after the development of macroproteinuria in patients with DKD,and that eventually some patients' condition may develop into end-stage renal disease(ESRD).Moreover,the thickening of the glomerular basement membrane,mesangial matrix expansion,Kimmelstiel-Wilson (K-W)nodules,and glomerulosclerosis in end-stage diabetes mellitus are typical pathologic changes of DKD.However,some DKD patients,especially those with type 2 diabetes mellitus(T2DM)combined with chronic kidney disease,may have diverse clinical manifestations,showing variations in disease progression and regression,and manifesting as non-classical types of DKD,such as normoalbuminuric DKD,proteinuria-reduced DKD,and DKD with rapid decline in renal function.In addition,the formation of crescents,a special pathological change,is observed in renal biopsy.However,this issue is currently under-recognized by clinicians and therefore deserves more attention.In order to improve clinicians' understanding of the presentations and pathological changes of non-classical DKD and the level of DKD prevention and treatment in China,we present a preliminary introduction to the clinical phenotypes and pathological changes of non-classical types of DKD in this paper by summarizing the findings of our prior studies as well as domestic and international literature.

Objective:To explore the safety and efficacy of EAC [etoposide+ cytarabine+ cyclophosphamide (CTX)] mobilization scheme for mobilizing stem cells in patients with lymphoma undergoing autologous hematopoietic stem cell transplantation (ASCT).Methods:A total of 36 patients with lymphoma who had collected peripheral blood stem cells through EAC or CTX+ granulocyte colony stimulating factor (G-CSF) mobilization scheme in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to March 2020 were retrospectively analyzed. Among them, 16 patients used EAC mobilization (EAC group), and 20 patients used CTX (CTX group). When white blood cells≤1.0×10 9/L, G-CSF (10 μg/kg per day) was given subcutaneously in two doses. The changes of hematology indexes, the number of collected cells, adverse reactions during mobilization collection and hematopoietic reconstitution after ASCT were observed. Results:The peripheral blood stem cells were collected on 5 d (3-8 d) after EAC+ G-CSF mobilization and 7 d (4-12 d) after CTX+ G-CSF mobilization. The success rates of collection in the EAC group and CTX group were 100% (16/16) and 75.0% (15/20) respectively, the high-quality collection rates were 87.5% (14/16) and 25.0% (5/20) respectively, and there were statistically significant differences ( P=0.041; P<0.001). The median of CD34 + cells of the two groups was 13.67×10 6/kg and 3.45×10 6/kg respectively, the median of mononuclear cells was 7.16×10 8/kg and 5.09×10 8/kg respectively, the median of CD34 + cells/mononuclear cells was 1.44% and 0.67% respectively, and there were statistically significant differences ( Z=-4.219, P<0.001; Z=-2.118, P=0.034; Z=-3.104, P=0.002). In the EAC group and CTX group, the incidences of grade 3 and above granulocytopenia were 100% (16/16) and 90.0% (18/20) respectively, the incidences of grade 3 and above hemoglobin reduction were 43.8% (7/16) and 25.0% (5/20) respectively, the incidences of grade 3 and above thrombocytopenia were 87.5% (14/16) and 65.0% (13/20) respectively, and there were no statistically significant differences ( P=0.492; P=0.298; P=0.245). There were no significant differences in the incidences of infection, adverse reactions of digestive system or other adverse reactions between the two groups (all P>0.05). All patients accepted improved Bucy scheme before ASCT. The median implantation time of neutrophils and platelets was 9.0 d and 10.5 d in the EAC group, which was 12.0 d and 13.5 d in the CTX group, and there were statistically significant differences ( Z=-4.698, P<0.001; Z=-3.757, P<0.001). Conclusion:EAC mobilization scheme can significantly increase the number of hematopoietic stem cell. This scheme has a high success rate of high-quality collection and the adverse reactions are within the controllable range. It provides a high-quality mobilization scheme for hematopoietic stem cell mobilization and collection, which is worthy of clinical promotion and application.