There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective To explore the mechanism of action of tanthine in the treatment of allergic rhinitis(AR)complicated with asthma in rats by regulating microRNA-27a-3p(miR-27a-3p)targeting thymic stromal lymphopoietin(TSLP).Methods The AR-asthma rat model was established using ovalbumin(OVA)sensitization and nasal drip attack method.Fifty rats were divided into control group(equal volume 0.9％NaCl),model group(AR-asthma model+equal volume 0.9％NaCl),experimental group(AR-asthma model+100 mg·kg-1 xanthortin)and miR-27a-3p inhibitor group(caudal vein injection of 0.5 nmol·μL-1 miR-27a-3p inhibitor 10 μL on the basis of the experimental group),si-TSLP group(0.5 nmol·μL-1 si-TSLP 10 μL intravenously injected on the basis of miR-27a-3p inhibitor group),10 rats in each group.Serum immunoglobulin E(IgE),interleukin-2(IL-2),IL-13 and tumor necrosis factor-α(TNF-α)levels of rats were detected by enzyme-linked immunosorbent assay.The level of superoxide dismutase(SOD)was detected by xanthoxine oxidase method.The level of malonaldehyde(MDA)was detected by thiobarbituric acid method(TBA).Results The levels of IgE in control group,model group,experimental group,miR-27a-3p inhibitor group and si-TSLP group were(18.33±3.53),(89.95±17.62),(55.70±10.08),(78.43±15.30)and(47.87±9.44)ng·mL-1,respectively;IL-2 levels were(8.01±1.36),(19.61±3.94),(14.12±2.51),(17.33±3.18)and(11.89±2.03)pg·mL-1,respectively;IL-13 levels were(6.79±1.33),(34.15±7.02),(24.70±5.13),(35.97±7.24)and(20.53±4.26)pg·mL-1,respectively;TNF-α levels were(94.08±19.07),(312.47±58.61),(209.78±41.49),(296.42±55.99)and(187.45±37.28)pg·mL-1,respectively;SOD levels were(29.14±5.04),(13.25±2.63),(24.19±4.89),(17.28±3.16)and(33.94±5.87)U·mg prot-1,respectively;MDA levels were(2.26±0.51),(4.43±0.72),(3.17±0.58),(3.94±0.69)and(2.62±0.45)nmol·m gprot-1,respectively.The above indicators were compared between control group and model group,model group and experimental group,experimental group and miR-27a-3p inhibitor group,miR-27a-3p inhibitor group and si-TSLP group.The differences were statistically significant(all P＜0.05).Conclusion Xanthine can improve oxidative stress and reduce inflammation of AR complicated with asthma in rats,and its mechanism may be related to the regulation of miR-27 a-3p targeting TSLP.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

Objective:To discuss the effect of exosomes(Exos)loaded with microRNA-520a-5p(miR-520a-5p)on the pregnancy outcomes in fetal mice with intrauterine growth restriction(FGR),and to clarify its mechanism.Methods:The mouse placental mesenchymal stem cells(MSCs)were cultured in vitro and transfected with miR-520a-5p adenovirus vector(Ad-miR-520a-5p)to obtain the Exos with high miR-520a-5p load(miR-520a-5p-MSCs-Exos),which were then identified.The C57BL/6 mice were mated in cages at a female∶male ratio of 2∶1 to achieve successful pregnancy.Forty pregnant mice were divided into control group,FGR group,NC-MSCs-Exos group,and miR-520a-5p-MSCs-Exos group,with 10 mice in each group.Except for control group,the mice in other groups were exposed to excessive dexamethasone(DEX)during pregnancy to induce FGR models in the pregnant mice.The body weights of the fetal mice at birth and at 1,2,3,and 4 weeks after birth were detected;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-520a-5p,DNA methyltransferase 3b(DNMT3b),and vascular endothelial growth factor(VEGF)mRNA in placenta tissue of the mice in various groups;Western blotting method was used to detect the expression levels of DNMT3b and VEGF proteins in placenta tissue of the mice in various groups;methylation-specific PCR(MSP)was used to analyze the methylation rates of VEGF promoter in placenta tissue of the mice in various groups;dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-520a-5p and DNMT3b.Results:The results of transmission electron microscope(TEM)and nanoparticle tracking analysis(NTA)showed that the Exos were spherical with particle size concentrated near 100 nm;the Western blotting method results showed that the surface biomarkers CD63 and CD81 of Exos were positively expressed.The RT-qPCR results showed that compared with NC-MSCs-Exos and Ad-NC-MSCs-Exos,the expression level of miR-520a-5p in Ad-miR-520a-5p-MSCs-Exos was increased(P＜0.001).The differences in birth body weight and the body weights at 1,2,and 3 weeks after birth of the fetal mice among four groups were statistically significant(F=36.084,F=19.851,F=77.755,F=103.223;P＜0.001).Compared with control group,the birth body weight and the body weights at 1,2,and 3 weeks after birth of the fetal mice in FGR group were decreased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the birth body weight and the body weights at 1,2,and 3 weeks after birth of the fetal mice in miR-520a-5p-MSCs-Exos group were increased(P＜0.05).The One-way ANOVA results showed that the differences in the expression levels of miR-520a-5p,DNMT3b,and VEGF mRNA in placenta tissue of the mice among four groups were statistically significant(F=103.224,F=856.460,F=214.563;P＜0.001).The pairwise comparison between groups showed that compared with control group,the expression levels of miR-520a-5p and VEGF mRNA in placenta tissue of the mice in FGR group were decreased(P＜0.05),and the expression level of DNMT3b mRNA was increased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the expression levels of miR-520a-5p and VEGF mRNA in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group were increased(P＜0.05),and the expression level of DNMT3b mRNA was decreased(P＜0.05).The One-way ANOVA results showed that the differences in the expression levels of DNMT3b and VEGF proteins in placenta tissue of the mice among four groups were statistically significant(F=245.601,F=149.360;P＜0.001).The pairwise comparison between groups showed that compared with control group,the expression level of DNMT3b protein in placenta tissue of the mice in FGR group was increased(P＜0.05),and the expression level of VEGF protein was decreased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the expression level of DNMT3b protein in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group was decreased(P＜0.05),and the expression level of VEGF protein was increased(P＜0.05).The One-way ANOVA results showed that the difference in the methylation rate of VEGF promoter in placenta tissue of the mice among four groups was statistically significant(F=687.096,P＜0.001).The pairwise comparison between groups showed that compared with control group,the methylation rate of VEGF promoter in placenta tissue of the mice in FGR group was increased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the methylation rate of VEGF promoter in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group was decreased(P＜0.05).Dual-luciferase reporter gene assay results showed that compared with miR-NC group,the luciferase activity in the cells containing DNMT3b-WT reporter vector in miR-520a-5p group was decreased(P＜0.05);compared with miR-NC group,the luciferase activity in the cells containing DNMT3b-MUT reporter vector in miR-520a-5p group had no change,no significant difference was observed(P＞0.05).Conclusion:The MSCs-derived Exos highly loaded with miR-520a-5p may improve the pregnancy outcomes of FGR fetal mice by targeting and down-regulating the expression of DNMT3b,inhibiting VEGF methylation,and promoting VEGF expression.