Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Acute lung injury （ALI） is a common and highly lethal clinical syndrome characterized by acute progressive respiratory failure. Currently， the treatment of ALI primarily involves respiratory support therapy and symptomatic pharmacotherapy， yet there is still a lack of specific and effective pharmacological treatments. Qingwen Baidu decoction is a traditional Chinese medicine formula that has the effects of clearing heat， removing toxin， cooling blood， and purging fire. Its pharmacological effects include anti-inflammatory， antipyretic， antibacterial， antiviral， sedative， and so on. The flavonoids， phenols， terpenes， and other components contained in this formula have strong pharmacological activity， which can regulate the inflammatory response caused and oxidative stress in ALI and maintain the integrity of alveolar-capillary barrier （ACB） by anti-apoptosis， anti-pathogen infection， and anti-pulmonary fibrosis， thereby improving the pathological changes of lung tissue. Among them， flavonoids have been reported more， and their mechanism of action is complex and diverse. For example， quercetin， luteolin， and baicalin act on multiple important targets， such as signal transducer and activator of transcription 3 （STAT3）， mitogen-activated protein kinase 3 （MAPK3）， etc. and participate in the regulation of Toll-like receptor 4 （TLR4）/myeloid differentiation primary response 88 （MyD88）/nuclear factor kappa B （NF-κB）， nuclear factor erythroid 2-related factor 2（Nrf2）/Kelch-like ECH-associated protein 1 （Keap1）， and silent information regulator 1 （SIRT1）/forkhead box protein O1 （FoxO1） signaling pathways， thereby intervening in pathological events such as inflammation， oxidative stress， cell apoptosis， and fibrosis. This paper aims to review the research progress on Qingwen Baidu decoction and its active ingredients in the prevention and treatment of lung injury in the expectation of providing reference for its subsequent pharmacological mechanism research and theoretical support for its clinical application and drug development in the treatment of ALI.

Background: Isoliquiritigenin, a key pharmacologically active compound derived from the traditional Chinese medicine Glycyrrhizae Radix et Rhizoma, can be further modified into various high-value 5-deoxyflavones, demonstrating significant potential for pharmaceutical development. Currently, the supply of isoliquiritigenin primarily depends on plant extraction. However, heterologous synthesis using microbial cell factories presents a promising alternative, offering a solution to resource limitations caused by the dwindling availability of Glycyrrhiza uralensis. Objective: This study aimed to employ heterologous synthesis in yeast strains for the stable and high-efficiency production of isoliquiritigenin. Methods: First, a stable chassis strain for isoliquiritigenin production was constructed by integrating optimized biosynthetic pathway enzyme genes. A type IV noncatalytic chalcone isomerase-like protein and a synthetic protein scaffold system were employed to enhance the metabolic channeling of key pathway enzymes. Subsequently, yeast metabolism was fine-tuned to balance precursor supply, and cofactor engineering strategies were implemented to increase nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) availability, thereby ensuring the catalytic efficiency of the key enzyme chalcone reductase. Results: The engineered strain Y21-2 achieved a 24.4-fold increase in isoliquiritigenin titer compared to the original strain. Additionally, the proportion of the by-product naringenin chalcone was reduced by 67.8%, marking the first instance in which the ratio of C-5 hydroxylated by-products was minimized to 10.4% during the microbial synthesis of 5-deoxyflavones. Conclusion: This work provides a valuable reference for the efficient and sustainable production of isoliquiritigenin, laying a solid foundation for further pathway optimization and the biotechnological synthesis of other high-value natural 5-deoxyflavones.

The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly di-vided into five groups:the control group(Control group),model 1 group(ACLT group),adminis-tration 1 group(ACLT+GC group),model 2 group(MIA group),and administration 2 group(MIA+GC group.)The rats were euthanized after 4 weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemis-try was used to detect the expression levels of collagen Ⅱ and MMP-13 in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-α in the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural dam-age to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13 in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory me-diators COX-2,IL-1β,and TNF-α were significantly lower in the ACLT group than in the MIA group(P＜0.0l).GC intervention reduced the OARSI score(P＜0.05 or P＜0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-11,COMP),and inflammatory mediators(COX-2,INOS,IL-1β and TNF-α)ex-pression,and promoted collagen Ⅱ synthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint dam-age,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the rat OA model in both groups,thus exerting a cartilage-protective effect.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

Objective:To search, evaluate and summarize the best evidence summary of perioperative accelerated rehabilitation nursing for patients undergoing hip and knee arthroplasty, so as to provide reference for clinical perioperative nursing.Methods:Evidence-based nursing methods were used to search for relevant databases such as BMJ Best Practice, UpToDate, PubMed, CINAHL, and CNKI, etc.. The search period was from December 2010 to December 2022. Four researchers independently evaluated the quality of the guidelines, and two researchers independently evaluated the quality of expert consensus and system evaluation. Finally, the included literature was summarized.Results:A total of 12 pieces of literature, 3 guidelines, 5 expert consensus and 4 systematic reviews were included. From 13 aspects of preoperative education, preoperative optimization, anesthesia management, perioperative blood management, perioperative pain management, perioperative fluid management, perioperative temperature protection, infection prevention, thrombus prevention, postoperative nausea and vomiting, postoperative drainage, functional exercise, and perioperative rehabilitation promotion, 35 pieces of the best evidence for hip and knee replacement patients to accelerate rehabilitation nursing in the perioperative period was summarized.Conclusions:This study summarizes the best evidence of accelerated rehabilitation nursing in the perioperative period of hip and knee arthroplasty, aiming to build and standardize the accelerated rehabilitation nursing scheme in the perioperative period of hip and knee arthroplasty, so as to provide reference for clinical perioperative nursing.

The health effects associated with environmental pollutants remain one of the major public health issues at present. The research method focusing on the population as the research subjects is limited by reliable cohorts, and the research method targeting individual molecules cannot fully reflect the biological health effects under environmental pollutant stress. Using high-throughput multi-omics, machine learning, and epigenetic detection to conduct targeted research and joint analysis on cells, organoids, organs, animals, and humans in different biological dimensions will help provide data support for the study of potential targets and biological effects of environmental pollutants, providing a theoretical basis for the risk assessment and safety evaluation of environmental pollutants.

Objective:To investigate the association between exposure to ambient air pollutants and pregnancy outcomes in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and to clarify the susceptible windows of exposure. Methods:A retrospective cohort study was conducted on 2 071 infertile women aged ≤40 years who underwent the first fresh cleavage stage embryo transfer in the Department of Reproductive Medicine of the First Affiliated Hospital of Harbin Medical University from January 2014 to December 2021. Patients were divided into heating season group and non-heating season group based on whether the start date of gonadotropin (Gn) was during the heating season or not, and baseline data and pregnancy outcomes were compared between the two groups. Daily average levels of six criteria air pollutants [fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), sulfur dioxide (SO 2), carbon monoxide (CO), ozone (O 3) max-8 h] in four discrete periods were obtained. The four discrete periods included period 1, 75 d prior to Gn start to Gn start; period 2, Gn start to oocyte retrieval; period 3, oocyte retrieval to day 3 embryo transfer; period 4, embryo transfer to serum human chorionic gonadotropin test. The primary outcome was ongoing pregnancy. A multiple logistic regression model was used to investigate the association between air pollutant exposure and pregnancy outcomes, adjusted for important confounders. Results:The biochemical pregnancy rate [51.7% (465/900)], the clinical pregnancy rate [45.2% (407/900)], the ongoing pregnancy rate [38.2% (344/900)], and the live birth rate [36.1% (325/900)] in the heating season group were significantly lower than those in the non-heating season group [56.3% (659/1 171), P=0.037; 51.2% (599/1 171), P=0.007; 44.3% (519/1 171), P=0.005; 41.3% (484/1 171), P=0.016]. A significant negative correlation was observed between SO 2 and NO 2 exposure and ongoing pregnancy in all four time windows. SO 2 increased by one interquartile range (IQR), corresponding to adjusted OR (a OR) and 95% CI were 0.92 (0.85-0.99), 0.92 (0.87-0.99), 0.93 (0.87-0.99) and 0.93 (0.87-0.99), respectively. An IQR increase in NO 2 was also significantly associated with decreased odds of ongoing pregnancy (a OR=0.83, 95% CI: 0.72-0.95; a OR=0.87, 95% CI: 0.77-0.97; a OR=0.90, 95% CI: 0.81-1.00; a OR=0.85, 95% CI: 0.77-0.95, respectively). During period 1 and period 4, we observed adverse effects of PM 10 exposure on ongoing pregnancy (a OR=0.86, 95% CI: 0.75-0.98; a OR=0.89, 95% CI: 0.80-1.00, respectively). In Period 1, PM 2.5 exposure was significantly associated with reduced odds for ongoing pregnancy with a OR=0.86, 95% CI: 0.75-0.99. In addition, NO 2 exposure was associated with a decreased likelihood of achieving clinical pregnancy across all exposure windows except for period 3. However, no associations were noted with CO and O 3. Conclusion:Ambient air pollution has detrimental effects on pregnancy outcomes in patients undergoing fresh embryo transfer. Notably, the adverse impacts were also observed during preantral-antral follicle transition stage before IVF/ICSI treatment. A significant negative association between NO 2 exposure and pregnancy outcomes was observed in almost all exposure windows, indicating that NO 2 may be the main air pollutant associated with adverse pregnancy outcomes.

Objective:To investigate the association between exposure to ambient air pollutants and pregnancy outcomes in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and to clarify the susceptible windows of exposure. Methods:A retrospective cohort study was conducted on 2 071 infertile women aged ≤40 years who underwent the first fresh cleavage stage embryo transfer in the Department of Reproductive Medicine of the First Affiliated Hospital of Harbin Medical University from January 2014 to December 2021. Patients were divided into heating season group and non-heating season group based on whether the start date of gonadotropin (Gn) was during the heating season or not, and baseline data and pregnancy outcomes were compared between the two groups. Daily average levels of six criteria air pollutants [fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), sulfur dioxide (SO 2), carbon monoxide (CO), ozone (O 3) max-8 h] in four discrete periods were obtained. The four discrete periods included period 1, 75 d prior to Gn start to Gn start; period 2, Gn start to oocyte retrieval; period 3, oocyte retrieval to day 3 embryo transfer; period 4, embryo transfer to serum human chorionic gonadotropin test. The primary outcome was ongoing pregnancy. A multiple logistic regression model was used to investigate the association between air pollutant exposure and pregnancy outcomes, adjusted for important confounders. Results:The biochemical pregnancy rate [51.7% (465/900)], the clinical pregnancy rate [45.2% (407/900)], the ongoing pregnancy rate [38.2% (344/900)], and the live birth rate [36.1% (325/900)] in the heating season group were significantly lower than those in the non-heating season group [56.3% (659/1 171), P=0.037; 51.2% (599/1 171), P=0.007; 44.3% (519/1 171), P=0.005; 41.3% (484/1 171), P=0.016]. A significant negative correlation was observed between SO 2 and NO 2 exposure and ongoing pregnancy in all four time windows. SO 2 increased by one interquartile range (IQR), corresponding to adjusted OR (a OR) and 95% CI were 0.92 (0.85-0.99), 0.92 (0.87-0.99), 0.93 (0.87-0.99) and 0.93 (0.87-0.99), respectively. An IQR increase in NO 2 was also significantly associated with decreased odds of ongoing pregnancy (a OR=0.83, 95% CI: 0.72-0.95; a OR=0.87, 95% CI: 0.77-0.97; a OR=0.90, 95% CI: 0.81-1.00; a OR=0.85, 95% CI: 0.77-0.95, respectively). During period 1 and period 4, we observed adverse effects of PM 10 exposure on ongoing pregnancy (a OR=0.86, 95% CI: 0.75-0.98; a OR=0.89, 95% CI: 0.80-1.00, respectively). In Period 1, PM 2.5 exposure was significantly associated with reduced odds for ongoing pregnancy with a OR=0.86, 95% CI: 0.75-0.99. In addition, NO 2 exposure was associated with a decreased likelihood of achieving clinical pregnancy across all exposure windows except for period 3. However, no associations were noted with CO and O 3. Conclusion:Ambient air pollution has detrimental effects on pregnancy outcomes in patients undergoing fresh embryo transfer. Notably, the adverse impacts were also observed during preantral-antral follicle transition stage before IVF/ICSI treatment. A significant negative association between NO 2 exposure and pregnancy outcomes was observed in almost all exposure windows, indicating that NO 2 may be the main air pollutant associated with adverse pregnancy outcomes.