ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

OBJECTIVE To evaluate the effectiveness and safety of warfarin anticoagulation therapy guided by gene test in patients undergoing left ventricular assist device （LVAD） implantation， and to analyze the influencing factors of warfarin anticoagulation efficacy. METHODS Patients who underwent LVAD implantation at the Heart and Vascular Center of Northern Jiangsu People’s Hospital from January 2023 to October 2024 and required warfarin anticoagulant therapy were selected as the study subjects. They were divided into genetic testing group （n＝51） and empirical treatment group （n＝17） based on whether they underwent CYP2C9 and VKORC1 gene test. The gene test group was given warfarin based on the predicted dose calculated by gene test， while the empirical treatment group was given warfarin by clinical doctors based on international normalized ratio （INR） experience， all patients were given warfarin once a day. Follow-up observation was conducted for 6 months to compare the effectiveness [time in therapeutic range（TTR）， the time required to reach INR for the first time， the incidence of embolic events， the incidence of INR＜1.5 events] and safety （the incidence of major and minor bleeding events，the incidence of INR＞3.5 events） of warfarin treatment between two groups of patients. According to whether the patient’s TTR was ≥60%， they were divided into TTR≥60% group （n＝20） and TTR＜60% group （n＝48）. Univariate and multivariate binary Logistic regression analysis were used to determine the factors affecting the anticoagulant effect of warfarin in patients. RESULTS The TTR of patients in the gene test group was significantly higher than that in the empirical treatment group （P＜0.05）. The incidence of INR＜1.5 events in the gene test group was significantly lower than in the empirical treatment group （P＜0.05）. The incidence of minor bleeding events and INR＞3.5 events in the gene test group were lower than in the empirical treatment group， but the difference was not statistically significant （P＞0.05）. The results of multivariate binary Logistic regression analysis showed that gene test was an independent protective factor for warfarin anticoagulant therapy [odds ratio （OR）＝10.842， 95% confidence interval （CI）： 1.211-27.037， P＝0.033]， and the combination of statins was an independent risk factor for warfarin anticoagulant therapy [OR＝0.196， 95%CI： 0.045-0.861， P＝0.031]. CONCLUSIONS Under the guidance of gene test， warfarin anticoagulation therapy for LVAD patients after implantation can improve TTR， shorten the anticoagulation target time， and has good safety； meanwhile， it should be noted that the combination of statins may enhance the anticoagulant effect of warfarin， thereby increasing the risk of bleeding in patients.

OBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens. METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity. RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine. CONCLUSION Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

Objective: To investigate the incidence and influencing factors of falls among the elderly in Ningbo City, Zhejiang Province, so as to provide the basis for developing effective prevention strategies. Methods: The residents aged 60 years and above in Haishu District and Yuyao City of Ningbo City were selected by the multi-stage cluster random sampling method from June to October 2022. Demographic information, fall incidence in the past year, history of disease and self-rated health were collected through questionnaire surveys. Incidence of falls was descriptively analyzed, and factors affecting falls were identified using a multivariable logistic regression model stratified by gender and age. Results: A total of 1 275 elderly people were surveyed, including 635 men and 640 women. The median age was 72.00 (interquartile range, 13.00) years. In the past year, 158 residents fell, accounting for 12.39%. Additionally, 14 individuals experienced two or more falls, accounting for 8.86%. The incidence of falls was 14.69% in women, which was higher than the 10.08% in men (P<0.05). The incidence of falls was 14.86% in the elderly over 70 years, which was higher than the 9.39% in those aged 60 to 70 years (P<0.05). Multivariable logistic regression showed that the educational level (primary school and above, OR=0.501, 95%CI: 0.301-0.836), heart disease (present, OR=1.996, 95%CI: 1.076-3.703), and self-rated health status (good, OR=0.529, 95%CI: 0.319-0.875) were factors affecting falls in women; educational level (primary school and above, OR=0.514, 95%CI: 0.285-0.928) and self-rated health status (good, OR=0.456, 95%CI: 0.253-0.824) were factors affecting falls in residents aged 60 to 70 years. Conclusion Fall risk among the elderly is associated with gender, age, heart disease, educational level and self-rated health status, and the influencing factors for falls vary in different genders and ages.

Objective: To assess the current situation and related factors of the knowledge, attitude and behavior toward sexual abuse prevention among primary school students in Luzhou City, Sichuan Province, so as to provide a reference basis for the development of sexual abuse prevention education for primary school students. Methods: A total of 4 563 primary school students in Luzhou City were sampled from December 2023 to January 2024 by stratified cluster sampling, and self administered questionnaires were conducted. The binary Logistic regression analysis was used to analyze related factors of the knowledge, attitude and behavior toward sexual abuse prevention. Results: The qualified rates of knowledge, behavior and attitude among primary school students towards sexual abuse prevention in Luzhou were 76.2%, 21.3%, and 90.2 %, respectively. The binary Logistic regression showed that males ( OR=0.66, 95%CI =0.56-0.78), attending rural schools ( OR=0.77, 95%CI =0.64-0.92), left behind status ( OR=0.66, 95%CI =0.53-0.81), and household registration in Lu County ( OR=0.57, 95%CI =0.46-0.70) and Gulin County ( OR=0.70, 95%CI =0.57-0.86) had lower qualified rates of the knowledge of sexual abuse prevention among primary school students ( P < 0.05 ); while qualified knowledge of sexual abuse prevention was positively associated with grade ( OR =3.05-18.81); attending rural schools ( OR=0.82, 95%CI =0.70-0.95) and not having received education on prevention of sexual abuse ( OR=0.55, 95%CI = 0.47-0.64) had lower qualified rates of the behavior of sexual abuse prevention among primary school students ( P <0.05); household registration in Lu County ( OR=0.73, 95%CI =0.58-0.92) and not having received education on prevention of sexual abuse ( OR=0.33, 95%CI =0.26-0.40) had lower qualified rates of the educational attitudes of sexual abuse prevention among primary school students ( P <0.05). Conclusions The qualified rates of knowledge and behavior of sexual abuse prevention among primary school students in Luzhou City needs to be improved. Health education regarding sexual abuse prevention might help enhance primary school students awareness and skills of sexual abuse prevention.

OBJECTIVE To establish the HPLC fingerprint and content determination of five components in Ranunculus sceleratus L.. METHODS The separation was developed on an Agilent ZORBAX SB C18 chromatographic (4.6 mm×250 mm, 5 μm)column by gradient elution with methanol(A)-0.1 % phosphoric acid aqueous solution(B) as mobile phase to establish HPLC fingerprint of Ranunculus sceleratus L.. Combined with similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis, the quality of 13 batches of Ranunculus sceleratus L. was evaluated. RESULTS Thirteen batches of Ranunculus sceleratus L. samples were calibrated with 20 common peaks, of which 5 common peaks were identified, and the similarity ranged from 0.874 to 0.984. The results of cluster analysis and principal component analysis were basically the same, indicating that there might be differences in the content of chemical components of Ranunculus sceleratus L. in different regions. Protocatechuic aldehyde, caffeic acid, ferulic acid, hyperoside and isoquercitrin were determined in thirteen batches of Ranunculus sceleratus L., and their contents were 0.016−0.035, 0.010−0.070, 0.010−0.029, 0.016−0.051, 0.028−0.086 mg·g–1, respectively. CONCLUSION The established HPLC fingerprint and content determination method is simple, stable, and reliable, which can be used for qualitative analysis and provide reference to quality evaluation and resource utilization of Ranunculus sceleratus L..

Objective To explore the establishment of a prognostic model based on machine learning algorithm to predict primary graft dysfunction(PGD)in patients with idiopathic pulmonary fibrosis(IPF)after lung transplantation.Methods Clinical data of 226 IPF patients who underwent lung transplantation were retrospectively analyzed.All patients were randomly divided into the training and test sets at a ratio of 7∶3.Using regularized logistic regression,random forest,support vector machine and artificial neural network,the prognostic model was established through variable screening,model establishment and model optimization.The performance of this prognostic model was assessed by the area under the receiver operating characteristic curve(AUC),positive predictive value,negative predictive value and accuracy.Results Sixteen key features were selected for model establishment.The AUC of the four prognostic models all exceeded 0.7.DeLong and McNemar tests found no significant difference in the performance among different models(both P＞0.05).Conclusions Based on four machine learning algorithms,the prognostic model for grade 3 PGD after lung transplantation is preliminarily established.The overall prediction performance of each model is similar,which may predict the risk of grade 3 PGD in IPF patients after lung transplantation.

Objective To investigate the expression of centromere protein U(CENPU)in the intestinal tissues of patients with colon cancer,and to analyze the effect of CENPU expression level on the prognosis of patients with colon cancer combined with bioinformatics.Methods Firstly,the expression of CENPU in cancer tissues and normal tissues of colon cancer patients was analyzed by the expression of CENPU in tissues was further verified by real-time quantitative real time polymerase chain reaction(qRT-PCR),Western blot(WB)and immunohistochemistry(IHC).Combined with clinical data,univariate and multivariate Cox regression are used to analyze the correlation between CENPU expression and clinical case parameters of colon cancer patients.Then,the predictive effect of CENPU expression on the prognosis of colon cancer patients are explored by drawing receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.Finally,the possible molecular mechanism of the effect of CENPU expression on the progression of colon cancer are analyzed by bioinformatics.Results By qRT-PCR,WB and IHC experiments,we find that compared with normal tissues,the expression of CENPU in cancer tissues of colon cancer patients is significantly increased.Cox regression analysis show that the expression of CENPU is significantly correlated with the age and TNM stage of patients,and is a risk factor affecting the prognosis of patients.Kaplan-Meier survival curve analysis show that colon cancer patients with high CENPU expression has significantly lower survival rates.ROC curve show that the model based on CENPU expression has a high predictive power for the prognosis of colon cancer patients area under the curve(AUC=0.832).Bioinformatics analysis show that CENPI,CENPN,CENPD,CENPK,CENPP,CENPM,CENPQ,CENPH,NDC80 and ITGB3BP have significant interaction with CENPU gene.CENPU is involved in DNA repair,MYC/TARGETS/V1 and PI3K/AKT/MTOR signaling pathways.Conclusion High expression of CENPU in cancer tissues of patients with colon cancer is significantly associated with poor prognosis of patients,suggesting that CENPU is expected to be a potential target for early diagnosis and prognosis prediction of patients with colon cancer.

Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

BACKGROUND:In clinical application,the therapeutic effect of transcranial magnetic stimulation depends on the ability to accurately target the areas of the brain that need to be stimulated.In recent years,with the development of neuronavigation systems,mobile augmented reality technology,and the new methods of processing magnetic resonance imaging(MRI)data,the accuracy of stimulus target localization and the optimization of target selection are expected to improve further. OBJECTIVE:To review the principle of MRI-based image navigation and its application in transcranial magnetic stimulation and summarize the roles of different modal MRI data analyses in guiding the selection of target areas for transcranial magnetic stimulation. METHODS:An online computer search for relevant literature was performed in PubMed,CNKI database and WanFang database,with the keywords"transcranial magnetic stimulation,coil positioning,neuronavigation,augmented reality,magnetic resonance,theory."Finally,63 documents were included for review. RESULTS AND CONCLUSION:Among the traditional methods of positioning transcranial magnetic stimulation coils,the"5 cm rule"and the international electroencephalogram 10-20 positioning method are the most commonly used.These methods have the advantages of simplicity and economy,but they rely too much on the operator's experience and there were technical differences between operators.The neuronavigation system,which is based on stereotactic technology,is the guiding method for positioning transcranial magnetic stimulation coils with the highest visual degree and accuracy.It achieves visual positioning through MRI data acquisition,3D brain reconstruction,head model registration and stereogeometric positioning.It has high application value in clinical treatment and scientific research,but it cannot be promoted in medical institutions due to its high cost.For various medical institutions,mobile augmented reality is a cost-effective and efficient alternative to the neuronavigation system,which achieves visual positioning of brain tissue under the scalp through MRI data acquisition,2D/3D image construction,virtual image and real brain image superposition.It has the advantages of directly visualization and low cost,and is expected to be popularized and applied in primary medical units.Although the superiority of clinical efficacy of visual coil positioning over the electroencephalogram 10-20 localization strategy has not yet been fully demonstrated,with the progress of brain MRI data analysis,visual positioning is expected to further optimize the target selection strategy of transcranial magnetic stimulation therapy and to improve the response rate and individuation degree of transcranial magnetic stimulation treatment.This is a promising and challenging research direction in the future.