Background Large-for-gestational-age (LGA) births are associated with adverse perinatal outcomes and increased risks of offspring obesity, metabolic syndrome, and cardiovascular diseases later in life. Beyond traditional risk factors, exposure to environmental factors, especially fine particulate matter (PM_2.5), before and during pregnancy may contribute to excessive fetal growth; however, the roles of specific chemical constituents and critical exposure windows remain unclear. Objective To examine the associations between maternal exposures to PM_2.5 and its chemical constituents before and during pregnancy and the risk of delivering LGA infants. Methods Singleton pregnancies from the National Free Preconception Health Examination Project between 2010 and 2014 were included. Individual exposures to PM_2.5 and its constituents were estimated for preconception and pregnancy windows using geocoded residential addresses. The associations of single and mixed exposures with LGA risk were analyzed using generalized linear models (GLMs) and qg-computation. Results Exposures to PM_2.5 and its major chemical constituents were significantly associated with an increased LGA risk, with differences in effect magnitude across components. Secondary inorganic aerosols showed the strongest associations. For full-pregnancy exposure, nitrate (OR=1.330, 95%CI: 1.313, 1.347), ammonium (OR=1.279, 95%CI: 1.263, 1.295), and sulfate (OR=1.242, 95%CI: 1.227, 1.257) had larger effects on LGA risk than black carbon and organic matter. Analysis by exposure window indicated that the month preceding conception and the third trimester of pregnancy were critical exposure windows for susceptibility, while the strongest effect was observed for full-pregnancy exposure, suggesting a cumulative effect over time. Mixed exposure analysis further showed that nitrate and sulfate consistently accounted for the main positive contributions across different time windows. Conclusion Maternal exposures to PM_2.5 and its chemical components before and during pregnancy are associated with an elevated LGA risk. Nitrate and sulfate show consistent and strong associations across pregnancy stages, underscoring the importance of component composition and exposure timing in fetal overgrowth.

Objective To explore the characteristics of the inhibitory effect of Evodiamine on the proliferation of activated T cells. Methods Mononuclear cells from peripheral blood (PBMCs) were obtained from healthy donors through density gradient centrifugation, and T cells were subsequently purified by using immunomagnetic bead separation. T cell activation was induced by employing anti-human CD3 and anti-human CD28 antibodies. T cells were treated with different concentrations of EVO (0.37, 1.11, 3.33, and 10)μmol/L. Flow cytometry was applied to evaluate the proliferation index, apoptosis rate, viability, CD25 expression levels, and cell cycle distribution of T cells. The expression levels of cytokines IL-2, IL-17A, IL-4, and IL-10 were quantified by using ELISA. Results 1.11, 3.33 and 10 μmol/L EVO effectively inhibited the proliferation of activated T cells, with an IC₅₀ of (1.5±0.3)μmol/L. EVO did not induce apoptosis in activated T cells and affect the survival rate of resting T cells. EVO did not affect the expression of CD25 and the secretion of IL-2 in activated T cells. EVO arrested the T cell cycle at the G2/M phase, resulting in an increase in G2/M phase cells, and exhibited a concentration-dependent effect. EVO did not affect the secretion of IL-4, IL-10 by activated T cells, but significantly inhibited the secretion of IL-17A. Conclusion EVO did not significantly affect the activation process of T cells but inhibited T cell proliferation by arresting the cell cycle at the G2/M phase and significantly suppressed the secretion of the pro-inflammatory cytokine IL-17A, which suggests that EVO has the potential to serve as a lead compound for the development of low-toxicity and high-efficiency immunosuppressants and elucidates the mechanisms underlying the anti-inflammatory and immunomodulatory effects of the traditional Chinese medicine Evodia rutaecarpa.
Humans ; Cell Proliferation/drug effects* ; Quinazolines/pharmacology* ; T-Lymphocytes/metabolism* ; Lymphocyte Activation/drug effects* ; Apoptosis/drug effects* ; Interleukin-4/metabolism* ; Interleukin-10/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-17/metabolism* ; Interleukin-2/metabolism* ; Cell Cycle/drug effects* ; Cells, Cultured

Objective:To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS).Method:A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ2 test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result:Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation ( P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×10 9/L vs. 3.5×10 9/L, P<0.001; mean before and after treatment in the membrane group: 3.5×10 9/L vs. 3.3×10 9/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×10 9/L vs. 119.6×10 9/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×10 9/L vs. 97.3 ×10 9/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion:Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.

Objective:To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS).Method:A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ2 test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result:Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation ( P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×10 9/L vs. 3.5×10 9/L, P<0.001; mean before and after treatment in the membrane group: 3.5×10 9/L vs. 3.3×10 9/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×10 9/L vs. 119.6×10 9/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×10 9/L vs. 97.3 ×10 9/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion:Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

Objective:To establish the biology reference interval (RI) of peripheral blood procalcitonin (PCT) for children between 3 days and 6 years old in China.Methods:Totally 3 353 reference individuals with apparent health or no specific diseases were recruited in 18 hospitals throughout the country during October 2020 to May 2021. Reference individuals were divided into four groups: 3-28 days, 29 days - 1 year, 1-3 years and 4-6 years. Vein blood or capillary blood were collected by percutaneous puncture from every reference individual. The PCT level in serum and the capillary whole blood were assayed by Roche Cobas e601 and Norman NRM411-S7 immunoanalyzer. Outliers were deleted and 95th percentiles of every group were provided as RIs. Man-Whitney U test or Kruskal-Wallis test were used performed to assess the difference among different gender, age or method groups. Results:The difference of PCT distribution between male and female is not statistically significant, but the difference between serum and capillary whole blood is statistically significant. The differences between age groups are significant too. For Roche e601, serum PCT RI of 3-28 days group is <0.23 μg/L, 29 days - 6 years are <0.11 μg/L. For NRM411, Serum PCT RI of 3-28 days group is <0.21 μg/L, 29 days - 1 year: <0.09 μg/L, 1 - 6 years: <0.10 μg/L. For whole blood PCT, RI of 3-28 days group is <0.26 μg/L, 29 days - 6 years is <0.15 μg/L.Conclusions:Serum and capillary whole blood PCT have different RIs, however, capillary whole blood PCT testing is valuable in pediatric application. Children in 3-28 days show higher PCT levels than other age group. To establish the RIs and understand the differences among different groups are essential for the interpretation and clinical application of peripheral blood PCT testing results.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,

Objective To study the inhibitory effects ofberberine on human organic cation transporter (OCTs) including OCT1,OCT2,OCT3,OCTN1 and OCTN2.Methods Using animal cell transgenic method mediated by transporter Lipo 3000,the drug transporters over expression cell lines S2-OCT1,S2-OCT2,S2-OCT3,S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture.The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro.Wild type (WT) cells were used as control group,activity of OCTs was verified by adding its inhibitor.The inhibition of berberine on the transporters was investigated in vitro.The IC50 of inhibitory effect of berberine on various drug transporters was also calculated.Result The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively,what's more,their transport activity decreased significantly by their corresponding inhibitor.The ICs0 of berberine to OCT1,OCT2,OCT3,OCTN1 and OCTN2 were respectively 7.63,6.80,2.25,4.66 and 210.34 μmol/L.Conclusion Berberine significant inhibition to OCT1,OCT2,OCT3,OCTN1 and OCTN2.The inhibition on OCT1,OCT2,OCT3,OCTN1 is stronger compared to OCTN2.

Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)％,(69.13±1.28)％,(72.12±3.28)％,(79.77±6.49)％,(69.51 ±5.99)％ and (38.4 ± 2.67)％ respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.