OBJECTIVE To investigate the effects of Brassica rapa polysaccharide （BRP） on the Toll-like receptor 4 （TLR4）/ myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1c （SREBP-1c） pathways， intestinal microbiota and liver metabolism of mice with alcoholic liver injury， and preliminarily elucidate its mechanism for improving alcoholic liver injury. METHODS Seventy-two mice were randomly divided into blank group （normal saline）， model group （normal saline）， bifendate group （positive control， 300 mg/kg） and BRP low-， medium- and high-dose groups （75， 150 and 300 mg/kg）. They were given relevant medicine intragastrically， once a day， for consecutive 9 d. After the last administration， mice in all groups except the blank group were gavaged with white liquor to establish an alcoholic liver injury model. The levels of alanine aminotransferase and aspartate aminotransferase in serum， total cholesterol， triglycerides， low-density lipoprotein cholesterol， interleukin-6， interleukin-1β， tumor necrosis factor- α and lipopolysaccharide， as well as protein expressions of TLR4， MyD88， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， AMPK， phosphorylated AMPK （p-AMPK）， and SREBP-1c were all detected； pathological morphological changes of liver tissue and colon were observed. 16S rRNA was used to detect the changes of intestinal microbiota in mice， and metabolomics 2022B02058） technology was used to detect the changes of liver metabolites. RESULTS Compared with model group， the above biochemical indicators and the protein expressions of TLR4， MyD88， p-NF-κB p65， and SREBP-1c in liver tissues were all significantly decreased （P＜0.05 or P＜0.01）， while the protein expression of p-AMPK was significantly increased （P＜0.05 or P＜0.01）. Pathological damage to liver and colon tissues was significantly improved. Medium dose of BRP could increase the relative abundance of Akkermansia， norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group in the intestinal contents of mice to a certain extent， and decrease the relative abundance of Lactobacillus and Escherichia-Shigella. A total of 9 differential metabolites were identified by metabolomics， including homogentisic acid， myristyl lysophosphatidylcholine， which were involved in pathways such as tyrosine metabolism. CONCLUSIONS BRP can regulate the relative abundance of beneficial flora， reduce the relative abundance of harmful flora， improve the structure of intestinal colonies， reduce the entry of pro-inflammatory mediator lipopolysaccharides into liver tissue， affect metabolic pathways such as tyrosine metabolism and the expression of TLR4/MyD88/NF- κB and AMPK/SREBP-1c signaling pathways in the liver， and ultimately improve alcoholic liver injury.

Excavating the quantitative trait locus (QTL) associated with rice cooking quality, analyzing candidate genes, and improving cooking quality-associated traits of rice varieties by genetic breeding can effectively improve the taste of rice. In this study, we used the indica rice HZ, the japonica rice Nekken2 and 120 recombinant inbred lines (RILs) populations constructed from them as experimental materials to measure the gelatinization temperature (GT), gel consistency (GC) and amylose content (AC) of rice at the maturity stage. We combined the high-density genetic map for QTL mapping. A total of 26 QTLs associated with rice cooking quality (1 QTL associated with GT, 13 QTLs associated with GC, and 12 QTLs associated with AC) were detected, among which the highest likelihood of odd (LOD) value reached 30.24. The expression levels of candidate genes in the localization interval were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), and it was found that the expression levels of six genes were significantly different from that in parents. It was speculated that the high expression of LOC_Os04g20270 and LOC_Os11g40100 may greatly increase the GC of rice, while the high expression of LOC_Os01g04920 and LOC_Os02g17500 and the low expression of LOC_Os03g02650 and LOC_Os05g25840 may reduce the AC. The results lay a molecular foundation for the cultivation of new high-quality rice varieties, and provide important genetic resources for revealing the molecular regulation mechanism of rice cooking quality.
Quantitative Trait Loci ; Oryza/genetics* ; Plant Breeding ; Cooking ; Genetic Association Studies

BACKGROUND:Mechanical factors can affect the angiogenic ability of vascular endothelial cells.How the vessel number affects the hydrodynamic properties of microvessels remains to be clarified. OBJECTIVE:To investigate the influence of vessel number on the hydrodynamics of vascular networks based on computational fluid dynamics. METHODS:Three three-dimensional models of vascular network with different vessel numbers were constructed using the Geometry module of ANSYS 19.0 software,and then the vascular network was meshed to tetrahedral elements in Mesh module.The vascular network was assumed to rigid wall without slip,and the blood was assumed to laminar,viscous,and incompressible Newtonian fluid.Blood density,velocity,and a series of blood viscosity coefficients were also established.The Navier-Stokes equation was used for calculation.Hydrodynamic properties of different parts of vascular network with different vessel numbers were analyzed and compared. RESULTS AND CONCLUSION:The streamline,velocity,and mass flow all had the same trend in the vascular network,that is,the outlet and inlet were higher and the middle junction of vascular network was lower.The more the number of vessels,the thinner the blood flow lines in each part of the vascular network.Also,the velocity,mass flow,and wall shear decreased with the increase of the number of blood vessels.Therefore,the changes in vessel number could influence the hydrodynamic environment in the vascular network.Computational fluid dynamics indicates that the changes in vessel numbers can influence the hydrodynamic properties of blood,and provides a new idea for treating bone hypoperfusion-induced diseases(fracture nonunion,bone defect,osteoporosis,etc.)through tonifying kidney and activating blood circulation based on the coupling between angiogenesis and osteogenesis.

Objective To investigate the antigen presentation characteristics of dendritic cells(DC)and B cells in cardiac grafts.Methods The heart of BALB/c mice was transplanted into the abdominal cavity of C57BL/6J mice.CD45+cells in the heart graft were extracted and sorted by flow cytometry at postoperative 5 d,and single cell RNA sequencing was performed.Taking DC and B cell subsets in cardiac grafts as the main study cells,the changing trend,antigen presenting ability and intercellular communication with T cells after heart transplantation were analyzed by bioinformatics analysis and flow cytometry.Gene ontology(GO)function enrichment difference analysis was adopted to prove the specific function and the reliability annotation of cell subsets.Results Germinal center-like B cell(GC-L B)was the B cell subset with the largest increase in quantity during the acute rejection phase,accounting for 87％.Classical DC(cDC)2 was the only DC subset with a significant increase in quantity during acute rejection of heart transplantation,accounting for 44％of DC subset,and it occupied the highest communication intensity with T cells after heart transplantation.Mononucleated DC(moDC)and memory B cell(MBC)were the main transmitters of T cell input signals in non-transplanted hearts,whereas transformed into cDC2 and GC-L B during the acute rejection phase.Among them,MBC and GC-L B were the main sources of T cell input signals in non-transplanted hearts and heart grafts.Conclusions Compared with DC,B cells occupy a higher number and weight in the intercellular communication with T cells in non-transplanted hearts and heart grafts,prompting that the antigen presenting activity of B cells is more active and stronger than DC in the early stage of acute rejection of heart transplantation.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Vascular remodeling is a physiological and pathological process in which abnormal changes in vas-cular cells and non-cellular components lead to the remodeling of inward and outward blood vessel wall or changes in lu-men diameter.As the channels for blood flow,blood vessels are continuously affected by hemodynamic forces.When sens-ing the abnormal blood flow forces,the mechanically sensitive cell membrane structures such as G protein-coupled recep-tors,ion channels,cell surface glycocalyx,and integrins,as well as the extracellular matrix will induce the process of vas-cular endothelial dysfunction,endothelial-mesenchymal transition,smooth muscle cell phenotypic switching,pericyte morphological changes and extracellular matrix remodeling to participate in vascular remodeling.As shown by research,abnormal hemodynamics caused abnormal changes in vascular structure and function,which was the basic process for the occurrence and development of pan-vascular diseases such as atherosclerosis,hypertension,diabetes,non-alcoholic fatty liver disease,pulmonary hypertension and COVID-19.This paper reviewed the interaction and molecular mechanism be-tween abnormal hemodynamics and vascular remodeling,and analyzed its influence on the pathogenesis of pan-vascular diseases,which could provide reference for formulating prevention and treatment strategies for pan-vascular diseases.

OBJECTIVE To investigate the intervention effects and potential mechanism of Miao medicine Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis （CIA） based on vitamin D （VD） and neutrophil extracellular traps （NETs）. METHODS SD rats were randomly divided into the normal group （9 rats） and the modeling group （61 rats）. CIA model was prepared by multi-point injection of type Ⅱ bovine collagen+Fisher’s incomplete adjuvant； the model rats were randomly divided into the model group， methotrexate group （positive control， 1.5 mg/kg， twice a week）， vitamin D group [pathway validation， 1 000 IU/（kg·d）， once a day]， T. asiatica low-dose， medium-dose and high-dose groups [0.54， 1.08， 2.16 g/（kg·d）， calculated by crude drug， once a day]， with 9 rats in each group； they were given relevant medicine intragastrically for 4 consecutive weeks. Arthritis index scoring was performed after modeling and before administration， and plantar thickness was measured before and after the last administration； the histopathological changes of ankle joint， heart and abdominal aorta were observed in rats； the serum contents of myeloperoxidase （MPO）， interleukin-6 （IL-6） and 25-hydroxyvitamin D3 [25（OH）D3] were detected； the expressions of peptidylarginine deiminase 4 （PAD4）， NETs markers [citrullinated histone H3（CitH3）， MPO]， VD-related indicators [vitamin D receptor （VDR）， 25-hydroxyvitamin D-1α-hydroxylase （CYP27B1）] and IL-6 were determined in cardiac tissue. RESULTS Compared with the normal group， the plantar thickness of the arthritis index increased significantly in the model group （P＜0.01）. The obvious inflammatory cell infiltration and fibrous tissue hyperplasia were found in the ankle joint， the obvious myocardial fiber （No.2019YFC171250101） vacuoles and thickening of some surrounding blood vessel walls were found in the heart tissue， and the endothelial detachment was found in the abdominal aorta. The contents of MPO and IL-6 in serum increased significantly（P＜0.01），while the level of 25（OH）D3 decreased significantly （P＜0.01）； the protein expressions of PAD4， CitH3， MPO and IL-6 in myocardial tissue up-regulated significantly （P＜0.01）， while protein expression of VDR and CYP27B1 changed to acertain extent without significance （P＞0.05）. Compared with the model group， the pathological changes of ankle joints and cardiac tissue in rats were significantly improved in administration groups， and the above indicators were generally reversed （P＜0.05 or P＜0.01）. CONCLUSIONS T. asiatica can improve rheumatoid arthritis symptoms and cardiovascular damage by inhibiting the formation of NETs and inflammatory response， the mechanism of which may be associated with the regulation of VD expression.

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA_1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA_1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.
Aged ; Blood Pressure ; China/epidemiology* ; Cholesterol, LDL/therapeutic use* ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/drug therapy* ; Glycated Hemoglobin A/analysis* ; Humans ; Male ; Middle Aged

Objective:To investigate the clinical, endoscopic and pathological characteristics of synchronous multiple early gastric cancer (SMEGC), and to reduce the rate of missed diagnosis.Methods:Clinical data of 227 early gastric cancer patients treated by endoscopic submucosal dissection (ESD) and/or surgery in Songjiang Hospital, Shanghai Jiaotong University School of Medicine from January 2017 to December 2019 were retrospectively analyzed. The differences of clinical, endoscopic and pathological characteristics between solitary early gastric cancer (SEGC) group (200 cases) and SMEGC group (27 cases) were compared. The relevance of endoscopic and pathological features of major and minor lesions of SMEGC was also analyzed.Results:Among the 227 early gastric cancer patients, 27 (11.9%) were SMEGC (58 lesions), of which 25 cases were detected preoperatively, and 2 cases were reexamined within 6 months after surgery with another lesion found at a different site from the previous lesion. In the SMEGC group, the percentages of male and atrophy and intestinal metaplasia in surrounding mucosa were significantly higher than those of the SEGC group [85.2% (23/27) VS 61.5% (123/200), χ2=5.815, P=0.016; 96.3% (26/27) VS 81.0% (162/200), χ2=3.912, P=0.048]. The mean age of the SMEGC group was significantly higher than that of the SEGC group (68.7±6.7 years VS 63.8±9.8 years, t=-2.561, P=0.011). The correlation analysis showed a significant correlation between the major and minor lesions of SMEGC in the size of lesion ( r=0.640, P<0.001), vertical location ( r=0.518, P=0.006), macroscopic type ( r=0.904, P<0.001) and depth of invasion ( r=0.470, P=0.013). Conclusion:SMEGC is prevalent in elderly males with atrophic gastritis and intestinal metaplasia. It is necessary to be alert to the possibility of multiple cancer lesions, if an early cancer lesion is found under endoscopy, especially those that may have the same or similar shape and invasion depth in the same vertical distribution range.

Objective To investigate the expressions of Toll-like receptors and NOD-like receptor (TLR/NLRP) in septic rats with acute kidney injury (AKI) and influence of Radix notoginseng. Methods One hundred and fifty male Sprague-Dawley (SD) rats were selected, and they were divided into three groups: sham operation group, model group and Radix notoginseng pretreatment group with 50 rats in each group. Sepsis rats with AKI models were established by cecal ligation puncture (CLP); only was laparotomy performed in the sham operation group without ligation. The rats in Radix notoginseng pretreatment group were given Radix notoginseng (3 g/kg) for consecutive 3 days by gastric perfusion before treatment, and the sham operation group and sepsis model group rats were given equal amount of normal saline by gastric perfusion. After their blood was collected, at each following time points 6, 12 and 24 hours after modeling, 10 rats in each group were sacrificed, and the kidney specimens were collected. The endotoxin levels were detected by limulus assay; the levels of serum creatinine (SCr) and urea nitrogen (BUN) were detected by automatic biochemical analyzer; serum levels of interleukins (IL-1β, IL-18, IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA); the expression levels of NLRP1/3 and TLR2/4 mRNA and protein in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western Blot, respectively; the pathological changes of renal tissues were observed by optical microscope. The 4-day and 7-day survival rates were observed in the remaining 20 rats in each group. Results The levels of endotoxin, SCr, BUN, IL-1β, IL-6, IL-18, and TNF-α and the expressions of NLRP1/3, TLR2/4 mRNA and proteins in sepsis model group and Radix notoginseng pretreatment group were significantly higher than those in sham operation group, and the levels of endotoxin, IL-18, and the expressions of NLRP1/3, TLR2/4 mRNA and proteins showed statistically significant differences at 6-hour after operation [endotoxin (kU/L): 61.3±25.7, 56.9±18.6 vs. 0.2±0.1, IL-18 (ng/L): 16.7±5.0, 13.8±2.9 vs. 10.6±2.8, NLRP3 mRNA (2-ΔΔCt): 6.3±1.9, 4.0±1.2 vs. 1.1±0.4, TLR mRNA (2-ΔΔCt): 5.7±1.3, 2.0±0.8 vs. 0.9±0.3, TLR4 mRNA (2-ΔΔCt): 4.4±1.2, 2.3±0.7 vs. 0.6±0.2, NLRP3/β-actin: 38.2±9.3, 26.1±7.2 vs. 18.3±5.1, TLR4/β-actin: 21.9±6.1, 16.2±4.4 vs. 10.9±2.8, TLR4/β-actin: 18.3±6.7, 12.0±3.9 vs. 7.5±2.0, all P < 0.05], the levels of SCr, BUN, IL-1β, TNF-α and IL-6 showed statistically significant differences at 12-hour after operation [SCr (μmol/L): 62.3±21.6, 38.1±13.9 vs. 36.0±11.9, BUN (mmol/L): 16.5±7.2, 6.9±2.6 vs. 6.8±2.5, IL-1β (ng/L): 37.6±10.9, 31.2±9.3 vs. 20.3±6.5, TNF-α (ng/L): 15.6±3.9, 10.2±2.8 vs. 7.3±2.1, IL-6 (ng/L):9.3±2.5, 6.8±1.7 vs. 5.0±1.3, all P < 0.05], the levels of expressions of NLRP3 mRNA and protein were obviously lower than those in sham operation group, and there were statistical significant differences immediately after 6-hour after operation [NLRP1 mRNA (2-ΔΔCt): 0.5±0.1, 0.8±0.2 vs. 1.6±0.5, NLRP3/β-actin: 8.0±2.1, 16.8±5.0 vs. 35.6±10.5, all P < 0.05], and the amplitude changes of the above indexes in Radix notoginseng pretreatment group were obviously smaller than those in sepsis model group (all P < 0.05); the survival rates of 4-day and 7-day in sepsis model group were significantly lower than those in sham operation group [4-day: 25% (5/20) vs. 95% (19/20), 7-day: 15% (3/20) vs. 95% (19/20), both P < 0.05], while the survival rate in Radix notoginseng pretreatment group was significantly higher than that in sepsis model group [respectively 65% (13/20) vs. 25% (5/20), 60% (12/20) vs. 15% (3/20), both P < 0.05]. Conclusions TLR2/4 and NLRP1/3 may be involved in the pathogenesis of AKI of septic rats. Traditional Chinese medicine Radix notoginseng possibly via regulating the expressions of TLR2/4 and NLRP1/3 can reduce the inflammatory response, in turn ameliorate kidney injury in septic rats and improve their renal functions.