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.

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*

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.

The main lysosomal protease cathepsin D (cathD) is essential for maintaining tissue homeostasis via its degradative function, and its loss leads to ceroid accumulation in the mammalian nervous system, which results in progressive neurodegeneration. Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis, cell proliferation, and migration. Along these lines, we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function. Upon cathD depletion, class I and class III arborization (da) neurons in Drosophila larvae exhibited aberrant dendritic morphology, including over-branching, aberrant turning, and elongation defects. Re-introduction of wild-type cathD or its proteolytically-inactive mutant dramatically abolished these morphological defects. Moreover, cathD knockdown also led to dendritic defects in the adult mushroom bodies, suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems. Taken together, our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.

Talaromyces marneffei is the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuD gene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffei by RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuD knockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffei yeast cells. After co-incubated at 28°C, the increasing T. marneffei inoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffei-zebrafish infection. Moreover, the results demonstrated that the virulence of the ΔAcuD was significantly attenuated in this Zebrafish infection model.
Gene Knockout Techniques ; Hyphae ; Isocitrate Lyase ; Microinjections ; Mortality ; Rhombencephalon ; RNA Interference ; Talaromyces ; Virulence ; Yeasts ; Zebrafish

Objective To investigate the association of serum ghrelin level with cognition, hippocampal volume, and proton magnetic resonance spectrum ( [ 1 H ]-MRS ) in patients with type 2 diabetes mellitus ( T2DM) . Methods The T2DM patients cared at the Wuhan Fourth Hospital were recruited. Data on demographic characteristics and clinical parameters were collected. Ghrelin was measured by ELISA assay. Cognitive performance was assessed by the Montreal Cognitive Assessment ( MoCA ) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The changes of metabolites in hippocampus were detected by [1 H]-MRS, including N-acetyl asparate ( NAA) , choline ( Cho) , myo-inositol ( MI) , creatine ( Cr) . All patients were divided into 2 groups[cognitive impairment (CI) and non-cognitive impairment (NCI) groups] by MoCA. Results (1) Compared with patients in NCI group, the serum ghrelin level, bilateral hippocampal volume, and NAA/Cr ratio of [1H]-MRS metabolites in CI group were decreased, but MI/Cr and Cho/Cr ratios were increased(all P<0.05). (2) Serum ghrelin was positively correlated with a variety of RBANS scores ( including immediate memory, attention, delayed memory, and total scores) , bilateral hippocampal volume, and NAA/Cr ratio of [ 1 H]-MRS metabolites in T2DM patients, but it was negatively correlated with MI/Cr ratio and Cho/Cr ratio ( all P<0. 05 ) . ( 3 ) Logistic regression analysis showed that ghrelin was a protective factor of cognition in T2DM patients. Conclusions T2DM patients with cognitive impairment had lower levels of ghrelin, and serum ghrelin was postively correlated with their cognitive performance, hippocampal volume, and [1 H]-MRS metabolites, suggesting that serum ghrelin may be involved in the occurrence and development of cognitive dysfunction in patients with T2DM.

Objective To establish the theoretical basis of the probiotic application among very low birth weight(VLBW) infants,the efficacy of probiotics on the gut microbiota of VLBW infants on the 14th postnatal day was studied.Method The VLBW infants admitted to BaoAn Maternal and Child Care Hospital from January 2015 to December 2015 were randomly assigned into probiotics group and placebo group.From the first feeding to corrected gestational age of 36 weeks,probiotics group was treated with a combination of Bifidobacterium and Lactobacillus while placebo group with placebo.Fecal samples were collected on the 1st and 14th postnatal day.Total bacterial DNA was extracted and sequenced using high-throughput 16S rRNA gene sequencing on MiSeq sequencing platform.Result A total of 21 VLBW infants were enrolled,9 in probiotics group and other 12 placebo group.No significant differences of clinical data existed between the two group (P ＞ 0.05),The abundance and diversity of microflora (P ＞ 0.05) on the first day between the two group were similar.Compared with placebo group,the relative abundance of Bifidobacterium and Lactobacillales in stool samples on the 14th day was significantly increased,while the Halomonas was significantly decreased.The relative abundance of the Shannon-index was increased,but without significant difference (P =0.16).Conclusion Enteral supplementation of probiotics in VLBW infants may increase probiotic bacterium and microflora diversity.

Objective:To observe the protective effect of deproteinized extract of calf blood (DECB)on the ethanol-induced liver injury of the mice,and to preliminaryly discuss its mechanism. Methods:Sixty healthy ICR mice were divided into control group,model group,positive drug group,low,medium and high doses of DECB groups (n=10).By intragastric administration,the mice in control group were given 20 mL·kg-1 saline solution, the mice in low,medium and high doses of DECB groups were administrated with 0.125,0.250,0.500 g·kg -1 DECB,and the mice in positive drug group were administrated with 0.63 g·kg -1 Hugan Tablets;once a day for 30 d. 1 h after the last administration,except control group,the mice in other groups were administrated with one-time grant of 50% ethanol 14 mL·kg -1 ,and fasted for 16 h to establish the models of acute alcohol liver injury.The endurance alcohol time and drunk time of the mice were determined,the activities of aspartate aminotransferase (ALT)and alanine transaminase (AST)activity in serum of the mice were detected,the levels of triglyceride (TG),glutathione (GSH)and malonic dialdehyde (MDA)in liver tissue were determined,and the pathological changes of liver tissue were detected.Results:Compared with model group,the drunk symptoms of the mice in different doses of DECB groups were obviously reduced,the endurance time of the mice in high dose of DECB group and positive drug group was prolonged (P <0.05),and the drinking time was shortened (P <0.05);the ALT and AST activities in serum in mediun and high doses of DECB groups were significantly lower than those in model group (P <0.05).Compared with model group,the MDA and TG levels in liver tissue of the mice in medium and high doses of DECB groups and positive drug group were obviously reduced,and the GSH levels were increased (P <0.05);compared with model group,the pathological damages of liver tissue of the mice in high dose of DECB group caused by ethanol were significantly reduced.Conclusion:DECB can improve ethanol-induced liver injury which may be related to the inhibition of hepatic oxidative stress response.

Objective To analyze the growth phenotype and blood biochemical parameters of chromosome 1 substi-tution mouse strain(CSS1), and investigate their potential of QTL mapping .Methods Body weight, body length, tail length, organ weight of the CCS1 mice were measured at different days to create a growth curve while blood biochemical in -dexes were measured at about the 80th day.Results The CCS1 mice were different from C57BL/6 mice in several inde-xes.Compared with the C57BL/6 mice during different developmental stages , six strains including B6-Chr1KM mice were significantly different in body weight .There were five strains including B6-Chr1CM mice significantly different with C57BL/6 mice in body length, and all of the CSS1 mice were significantly different from C57BL/6 mice in tail length.Part of CCS1 mice were significantly different from C57BL/6 mice in the weight of liver, spleen, kidney and brain.The ALT of female B6-Chr1CM mice was significantly higher than that in the C 57BL/6 mice.The ALP of female B6-Chr1HZ mice was signifi-cantly higher than that in the male C57BL/6 and B6-Chr1KM mice, and was significantly lower than that in the C57BL/6 mice.The TB of male B6-Chr1CM, B6-Chr1SMX and B6-Chr1HZ mice was significantly higher than that of the C 57BL/6 mice.The TG of male B6-Chr1SMX mice and male B6-Chr1TW mice was significantly higher than that in the C 57BL/6 mice. Conclusions The phenotype of Chr1 CSS mice is quite different from commonly used inbred strain C 57BL/6 mice.CCS1 mice show great potential in QTL mapping for their characteristic growth phenotype and blood biochemical indexes .