ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

In recent years, the spread of clubroot disease caused by Plasmodiophora brassicae infection has seriously affected the yield and quality of Brassica juncea (L.) Czern.. The cascade of mitogen-activated protein kinases (MAPKs), a highly conserved signaling pathway, plays an important role in plant responses to both biotic and abiotic stress conditions. To mine the MAPK genes related to clubroot disease resistance in B. juncea, we conducted a genome-wide analysis on this vegetable, and we analyzed the phylogenetic evolution and gene structure of the MAPK gene family in mustard. The 66 BjuMAPK genes identified by screening the whole genome sequence of B. juncea were unevenly distributed on 17 chromosomes. At the genomic scale, tandem repeats led to an increase in the number of MAPK genes in B. juncea. It was found that members of the same subfamily had similar gene structures, and there were great differences among different subfamilies. These predicted cis-acting elements were related to plant hormones, stress resistance, and plant growth and development. The expression of BjuMAPK02, BjuMAPK15, BjuMAPK17, and BjuMAPK19 were down-regulated or up-regulated in response to P. brassicae infection. The above results lay a theoretical foundation for further studying the functions of BjuMAPK genes in B. juncea in response to the biotic stress caused by clubroot disease.
Mustard Plant/parasitology* ; Plasmodiophorida/pathogenicity* ; Plant Diseases/genetics* ; Mitogen-Activated Protein Kinases/metabolism* ; Phylogeny ; Disease Resistance/genetics* ; Gene Expression Regulation, Plant ; Genome, Plant ; Plant Proteins/genetics*

ObjectiveTo evaluate the clinical effectiveness and safety of Modified Zhigancao Granules （炙甘草汤加味颗粒） for preventing the early recurrence following radiofrequency ablation in patients with atrial fibrillation （AF） of qi-yin deficiency syndrome. MethodsA multi-center， randomized， double-blind， placebo-controlled trial was designed. A total of 116 patients with atrial fibrillation of qi-yin deficiency syndrome who underwent radiofrequency ablation for the first time were enrolled from 3 centers， and they were randomly divided into a treatment group （59 cases） and a control group （57 cases）. Both groups received basic western medicine treatment after surgery. In addition， the treatment group was given oral Modified Zhigancao Granules， while the control group was given oral placebo granules. The dosage for both groups was 20 g each time， twice a day， with continuous treatment for 12 weeks. The recurrence of atrial fibrillation in both groups was recorded at 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery. The serum levels of B-type natriuretic peptide （BNP）， interleukin-6 （IL-6）， high-sensitivity C-reactive protein （hs-CRP）， and tumor necrosis factor-α （TNF-α） were detected before treatment and 12 weeks after treatment in both groups. The scores of Atrial Fibrillation Effect on QualiTy-of-life （AFEQT） Questionnaire （including scores of the daily life dimension， symptom dimension， treatment worry dimension， treatment satisfaction dimension， and total score） and traditional Chinese medicine （TCM） syndrome scores were compared before treatment and at 4 weeks， 8 weeks， and 12 weeks between groups. Safety indicators such as blood routine， urine routine， liver function， and renal function were monitored before and after treatment. ResultsNine of the treatment group and seven of the control group dropped out. Finally， 50 patients in each group were included in the statistical analysis. At 24 hours， 4 weeks， 8 weeks， and 12 weeks after surgery， the recurrence rates of AF in the treatment group were 2.0% （1/50）， 2.0% （1/50）， 4.0% （2/50）， and 10.0% （5/50）， respectively； while those in the control group were 2.0% （1/50）， 26.0% （13/50）， 28.0% （14/50）， and 34.0% （17/50）， respectively. Compared with the control group at the same time points， the early recurrence rates of AF in the treatment group were significantly lower at 4 weeks， 8 weeks， and 12 weeks after surgery （P＜0.01）. Compared with the baseline within group， BNP， hs-CRP， IL-6， and TNF-α in the treatment group all decreased after 12 weeks of treatment （P＜0.05）； the difference in hs-CRP levels （before vs. after treatment） in the treatment group was higher than that in the control group （P＜0.01）. Compared with the baseline within group， both groups showed decreases in the total score of AFEQT Questionnaire， scores of the daily life dimension， treatment worry dimension， symptom dimension， and TCM syndrome scores at 4 weeks， 8 weeks， and 12 weeks after treatment. Meanwhile， the score of the treatment satisfaction dimension of AFEQT increased in both groups （P＜0.01）， and the improvements in all the above scores in the treatment group were superior to those in the control group at all time points （P＜0.05 or P＜0.01）. All safety indicators of patients in both groups were within the normal range before treatment and at 12 weeks after treatment， and no adverse reactions or adverse events occurred in either group. ConclusionModified Zhigancao Granules can reduce the early recurrence rate following radiofrequency ablation in AF patients with qi-yin deficiency syndrome， improve clinical symptoms and quality of life， suppress inflammatory response， and show good safety.

Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

Leukemia is a malignant proliferative tumor that seriously endangers the quality of life of patients. In recent years, new research achievements have been made on the pathogenesis of leukemia, and some progresses of various drugs targeting the hypoxic microenvironment of leukemia have been made. This article reviews the progress of drugs targeting hypoxia microenvironment to treat leukemia from the aspects such as reactive oxygen species associated with anoxic microenvironment, hypoxia inducible factor, CXC chemokine receptor and vascular endothelial growth factor.

Objective To investigate the early predictive value of combined detection of serum sodium,heparin-binding protein-to-albumin ratio(HBP/ALB)and interleukin-10(IL-10)in Ka-wasaki disease shock syndrome(KDSS)caused by Kawasaki disease in children.Methods A total of 105 children with KDSS caused by Kawasaki disease(KDSS group)and 105 children with Kawasa-ki disease(control group)were selected as study subjects.Clinical data,serum sodium levels,HBP/ALB and IL-10 levels were compared between the two groups.Multivariate logistic regression a-nalysis was used to screen the influencing factors of KDSS caused by Kawasaki disease in children a-mong serum sodium,HBP/ALB and IL-10.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the predictive value of traditional prediction schemes(coronary artery dam-age and IVIG resistance)and new prediction schemes(serum sodium and HBP/ALB,IL-10)for KDSS caused by Kawasaki disease in children.Results The proportion of patients with coronary ar-tery damage and IVIG resistance was significantly higher in the KDSS group than those in the control group(P＜0.05).Serum sodium levels were lower,while HBP/ALB and IL-10 levels were higher in the KDSS group compared to the control group(P＜0.05).Multivariate logistic regression analysis showed that serum sodium,BP/ALB and IL-10 were influencing factors of KDSS caused by Kawasaki diseasein children(P＜0.05).For traditional prediction schemes,the areas under the curves(AUCs)for coronary artery damage,IVIG resistance and their combination in predicting KDSS caused by Kawasaki disease were 0.795,0.676 and 0.873,respectively(P＜0.05);for new prediction schemes,the AUCs for serum sodium,HBP/ALB,IL-10 and their combination in predicting KDSS were 0.767,0.824,0.760 and 0.945,respectively(P＜0.05).The AUC for the combination of serum sodium,HBP/ALB and IL-10 was greater than that for the combination of coronary artery dam-age and IVIG resistance(P＜0.05).Conclusion Decreased serum sodium,elevated HBP/ALB and elevated IL-10 are associated with KDSS caused by Kawasaki disease in children.Combined prediction using serum sodium,HBP/ALB and IL-10 has a high predictive value for KDSS caused by Kawasaki disease in children.

Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Objective To construct the triple pre-rehabilitation program for the patients undergoing pancreaticoduodenectomy to provide a theoretical basis for the preoperative management of this operation mode.Methods The raft plan was formed by the literature research and group discussion,then the experts were invited to conduct the two rounds of expert consultation,and the final draft of the plan was finally formed.Results The draft plan included the 3 first-level items,9 second-level items and 28 third-level items.The questionnaire recovery rate of the two rounds of expert correspondence was 100%,and the authority coef-ficients were 0.88 and 0.93,respectively.The mean importance and feasibility scores of each item in the two rounds of expert consultation were ≥3.5,and the coefficient of variation was<0.25.The first draft of the final formation plan included the 3 first-level items,9 second-level items and 31 third-level items.Conclusion This program has ne-cessity,scientificity and feasibility.Clarifying the specific contents and scope of preoperative management of this operation mode could provide a theoretical basis for medical staff to carry out pre-rehabilitation.