Objective To understand the current situation and influencing factors of delirium in lung transplant patients in the early postoperative period,and to construct and verify a risk prediction model.Methods The convenience sampling method was used to select patients who were admitted to a tertiary general hospital in Jiangsu Province for lung transplantation from June 2023 to November 2024.Lasso regression was used to screen variables,and logistic regression analysis was used to explore the influencing factors of early postoperative delirium in lung transplantation patients,and the risk prediction model was constructed and nomogram was drawn.The area under the working curve(AUC)of the subjects and the Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Internal validation of the model was performed by repeated sampling 1000 times using Bootstrap method.Results A total of 228 lung transplant patients were included in this study,of which 76 developed delirium in the early postoperative period,with an incidence of 33.33％.Age≥51.5 years,hypertension combined with diabetes mellitus,the Lung Allocation System(LAS)score ≥ 75.63,the duration of mean arterial pressure less than 70 mmHg≥ 12.50 min,intraoperative red blood cell transfusion≥750 ml,and midazolam dosage≥102.50 mg were the independent risk factors for early postoperative delirium in lung transplantation(P＜0.05).The AUC of the model was 0.771;the optimal cut-off value was 0.334;the sensitivity and specificity were both 0.724.The results of Hosmer-Lemeshow test showed that x2=5.677,P=0.683;the internal verification showed that the AUC of the model was 0.737,and the absolute error of the actual and predicted values of the calibration curve was 0.023,and the calibration curve was close to the ideal curve.Conclusion Age,hypertension combined with diabetes mellitus,LAS score,duration of mean arterial pressure less than 70 mmHg,amount of intraoperative red blood cell transfusion,and midazolam dosage are the influencing factors for early postoperative delirium in lung transplant patients.The risk prediction model constructed in this study has good predictive performance and can be used as a risk prediction tool for early postoperative delirium in lung transplant patients,helping to timely and accurately identify high-risk groups of delirium,helping to reduce the incidence of early postoperative delirium,and improve patient prognosis.

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

Objective:To observe the effect of high-intensity interval training (HIIT) on diabetic rats with non-alcoholic fatty liver disease (NAFLD), and to explore the role of miR-122 in it.Methods:Forty Wistar rats were randomly divided into a healthy control group, a sedentary group, a high-intensity interval training (HIIT) group and a moderate-intensity continuous training (MICT) group using a random number table. All except the healthy control group had type 2 diabetes with NAFLD induced using a high-fat and high-fructose diet. The healthy control and sedentary groups were kept quiet in their cages, while the HIIT and MICT groups performed treadmill exercise of the corresponding intensity for 8 consecutive weeks. At 48h after the last training, plasma was collected to measure biochemical markers, and the livers were resected for histological observation using hematoxylin and eosin staining. miR-122 expression was measured using real-time fluorescent quantitative polymerase chain reactions, while the protein expressions of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), sterol regulatory element binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor γ (PPARγ) were detected using western blotting.Results:Compared with the healthy control group, the average fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin and insulin resistance index (HOMA-IR) had increased significantly in the sedentary group. Compared with the sedentary group, the average FBG, TG, TC, insulin and HOMA-IR had decreased significantly in both the HIIT and MICT groups, and the average ALT and AST in the HIIT group had also decreased significantly. The average TG, TC, ALT and AST levels in the HIIT group were then significantly lower than in the MICT group. Compared with the sedentary group, the average liver steatosis score had decreased significantly in both the HIIT and MICT groups, with that of the HIIT group significantly lower than in the MICT group, on average. Compared with the healthy control group, the expression of miR-122 had decreased significantly, but that of SREBP1c, PPARγ, FAS and ACC had increased significantly in the sedentary group. And compared with the sedentary group, the expression of miR-122 had increased significantly in both the HIIT and MICT groups, on average, but that of SREBP1c, PPARγ, FAS and ACC had decreased significantly. Average miR-122 levels in the HIIT group were then significantly higher, and those of SREBP1c, PPARγ, FAS and ACC were significantly lower than in the MICT group.Conclusions:Either MICT or HIIT training can relieve NAFLD in rats modeling diabetes, but HIIT has a better therapeutic effect. Its therapeutic mechanism may be related to the upregulation of miR-122 in the liver.

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

Objective To retrieve the academic documents concerning vein of Marshall(VOM)published in the years of 2000-2023 from Web of Science database,to summarize the literature,to make visualization analysis,and to judge the development status of this field.Methods The core collection expansion database in Web of Science database was used as the data source,the VOM-related literature published in 2000-2023 was collected.the R software was used to make descriptive bibliometric analysis,and software tools such as CiteSpace,VOSviewer,etc.were used to make interpretation of the visualization results.Results A total of 145 documents were retrieved,which were published in 34 journals and were written by 816 researchers from 227 research institutions in 17 countries.The number of publications continued to increase since 2000,especially,the number of publications presented an explosive growth since 2019.The United States dominated in the number of published literature and the number of documents cited,besides,the University of California,Los Angeles was considered the most active research institution with the largest total number of citations(n=587).The《JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY》had the highest number of annual publications and the most total local citations.Duchateau was one of the most active researchers in this field in recent years,and Hwang was one of the earliest and most influential researchers in this field.The timeline analysis indicated that"mitral isthmus ablation"was the most important area of VOM research.In recent years,persistent atrial fibrillation and absolute ethanol perfusion ablation were the hottest research directions.Conclusion In this study,bibliometric analysis is used to analyze VOM-related literature,comprehensively and intuitively expounds the research hotspots and research directions in this field,providing effective reference information for further studies.

This paper reported a case of 77-year-old male patient who developed generalized ery-thematous macules,bullae and erosion,accompanied by genital mucosa involvement five days after taking compound sulfamethoxazole tablets.Based on patient's clinical manifestations and auxiliary ex-amination results,the diagnosis of generalized bullous fixed drug eruption was confirmed.Clinicians should be vigilant about generalized bullous fixed drug eruption with genital mucosa involvement and strive for early detection,diagnosis,and treatment.

Objective To explore the effect of project-based learning on the training of sharp injury prevention skills in the pre-job training for nursing interns and its impact on the incidence of sharp injuries during internship.Methods Two classes(class A and B),majoring in nursing at Medical College of Nanchang Institute of Technology in March 2023 were selected as the research subjects by convenience sampling method.Coin flipping method was used to designate class A as the routine group and class B as the intervention group.The routine group received rou-tine pre-job training which mainly focused on retrospective intensive training on nursing operation skills.On this ba-sis,the intervention group integrated project-based learning as compensation education on sharp injury prevention skills.Kirkpatrick's four level training evaluation model was adopted to comprehensively evaluate the educational effectiveness at the four progressive levels of"reaction,learning,behavior,and outcome"at corresponding stages.Results 56 nursing interns were included in the class A routine group and class B intervention group,respectively.The course evaluation score(128.67±4.39 vs 117.28±6.55),needlestick protection knowledge cognition score(109.11±4.38 vs 96.44±6.72),safe injection behavior score(38.45±4.91 vs 32.30±5.62),occupational iden-tity score(58.02±8.55 vs 51.77±15.86),and job competency score(82.59±13.35 vs 75.61±15.09)of nursing interns in the intervention group were all higher than those in the routine group,differences were all statistically sig-nificant(all P＜0.05).The incidence of sharp injuries(19.64％ vs 57.14％)and the average frequency of occu-rrence(1.45 vs 2.13)in nursing interns in the intervention group were both lower than those in the control group.The case intervention rate(87.50％ vs 45.59％)and case reporting rate(93.75％vs 32.35％)after sharp injury were both higher than those in the routine group,and the differences were both statistically significant(both P＜0.05).Conclusion Introducing project-based learning in pre-job training for nursing interns can effectively improve their mastery of protection skills,reduce the incidence of sharp injuries during internships,and have important prac-tical value in cultivating their occupational protection abilities.

This study was aimed at evaluating the characteristics of H9N2 subtype avian influenza viruses(AIVs)origina-ting from wild birds in major wetlands in Fujian.Five H9N2 subtype AIVs isolated from fecal samples from wild birds in wet-lands of the Minjiang River,Jiulong River,Sandu Bay,Xinghua Bay,and Quanzhou Bay in Fujian were sequenced.Sequence a-nalysis of the HA genes of the five H9N2 subtype AIVs indicated that the five isolates shared 89.8％-99.4％nucleotide se-quence identity.All five isolates belonged to the same h9.4.2.5c evolutionary branch.The cleavage site motifs of HA were all PSRSSR ↓ GLF,thus indicating molecular characteristics of AIVs with low pathogenicity.The HA proteins of the viruses orig-inating from wild birds bore eight identical potential glycosylation sites,among which the glycosylation site at position 313 was located near the HA protein cleavage site.The 226th amino acid of HA in the receptor binding site was leucine in each virus,thus indicating that HAs of the five H9N2 subtype AIVs had mammalian sialic acid α-2,6 receptor binding affinity.In conclu-sion,the five H9N2 subtype AIVs originating from wild birds in Fujian had low pathogenicity,and the HAs had mammalian sialic acid α-2,6 receptor binding affinity.

Objective To explore the effect of project-based learning on the training of sharp injury prevention skills in the pre-job training for nursing interns and its impact on the incidence of sharp injuries during internship.Methods Two classes(class A and B),majoring in nursing at Medical College of Nanchang Institute of Technology in March 2023 were selected as the research subjects by convenience sampling method.Coin flipping method was used to designate class A as the routine group and class B as the intervention group.The routine group received rou-tine pre-job training which mainly focused on retrospective intensive training on nursing operation skills.On this ba-sis,the intervention group integrated project-based learning as compensation education on sharp injury prevention skills.Kirkpatrick's four level training evaluation model was adopted to comprehensively evaluate the educational effectiveness at the four progressive levels of"reaction,learning,behavior,and outcome"at corresponding stages.Results 56 nursing interns were included in the class A routine group and class B intervention group,respectively.The course evaluation score(128.67±4.39 vs 117.28±6.55),needlestick protection knowledge cognition score(109.11±4.38 vs 96.44±6.72),safe injection behavior score(38.45±4.91 vs 32.30±5.62),occupational iden-tity score(58.02±8.55 vs 51.77±15.86),and job competency score(82.59±13.35 vs 75.61±15.09)of nursing interns in the intervention group were all higher than those in the routine group,differences were all statistically sig-nificant(all P＜0.05).The incidence of sharp injuries(19.64％ vs 57.14％)and the average frequency of occu-rrence(1.45 vs 2.13)in nursing interns in the intervention group were both lower than those in the control group.The case intervention rate(87.50％ vs 45.59％)and case reporting rate(93.75％vs 32.35％)after sharp injury were both higher than those in the routine group,and the differences were both statistically significant(both P＜0.05).Conclusion Introducing project-based learning in pre-job training for nursing interns can effectively improve their mastery of protection skills,reduce the incidence of sharp injuries during internships,and have important prac-tical value in cultivating their occupational protection abilities.

Objective To understand the current situation and influencing factors of delirium in lung transplant patients in the early postoperative period,and to construct and verify a risk prediction model.Methods The convenience sampling method was used to select patients who were admitted to a tertiary general hospital in Jiangsu Province for lung transplantation from June 2023 to November 2024.Lasso regression was used to screen variables,and logistic regression analysis was used to explore the influencing factors of early postoperative delirium in lung transplantation patients,and the risk prediction model was constructed and nomogram was drawn.The area under the working curve(AUC)of the subjects and the Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Internal validation of the model was performed by repeated sampling 1000 times using Bootstrap method.Results A total of 228 lung transplant patients were included in this study,of which 76 developed delirium in the early postoperative period,with an incidence of 33.33％.Age≥51.5 years,hypertension combined with diabetes mellitus,the Lung Allocation System(LAS)score ≥ 75.63,the duration of mean arterial pressure less than 70 mmHg≥ 12.50 min,intraoperative red blood cell transfusion≥750 ml,and midazolam dosage≥102.50 mg were the independent risk factors for early postoperative delirium in lung transplantation(P＜0.05).The AUC of the model was 0.771;the optimal cut-off value was 0.334;the sensitivity and specificity were both 0.724.The results of Hosmer-Lemeshow test showed that x2=5.677,P=0.683;the internal verification showed that the AUC of the model was 0.737,and the absolute error of the actual and predicted values of the calibration curve was 0.023,and the calibration curve was close to the ideal curve.Conclusion Age,hypertension combined with diabetes mellitus,LAS score,duration of mean arterial pressure less than 70 mmHg,amount of intraoperative red blood cell transfusion,and midazolam dosage are the influencing factors for early postoperative delirium in lung transplant patients.The risk prediction model constructed in this study has good predictive performance and can be used as a risk prediction tool for early postoperative delirium in lung transplant patients,helping to timely and accurately identify high-risk groups of delirium,helping to reduce the incidence of early postoperative delirium,and improve patient prognosis.