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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

The high incidence of bleeding after peripherally inserted central catheter (PICC) catheterization increases the risk of puncture site infection and unplanned extubation. Hemostatic dressings should be used in the early stages of catheterization to reduce blood infiltration. However, new hemostatic dressings have various types and advantages, which makes them difficult to choose dressings for medical staff. This paper introduces the types and hemostatic characteristics of novel functional hemostatic dressings, reviews the hemostatic mechanism and hemostatic effect of chitosan, cyanoacrylate gum, alginate, gelatin sponge and oxycellulose dressings in PICC puncture respectively, and prospects the development of new functional hemostatic dressings. It is expected that future hemostatic dressings will move towards multifunctionality and compositeness.
Humans ; Bandages ; Catheterization, Peripheral/instrumentation* ; Hemorrhage/prevention & control* ; Hemostatics/therapeutic use*

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*

Purpose To develop and validate a radiomics-clinical model that could accurately predict the recurrence of hepatocellular carcinoma(HCC)after undergoing tumor resection.Materials and Methods A total of 311 HCC patients underwent tumor resection in the Affiliated Hospital of North Sichuan Medical College from January 2015 to June 2022 were retrospectively collected,and they were randomly divided into a training cohort(n=217)and a validation cohort(n=94)in the ratio of 7∶3.Tumor and peritumoral 5 mm regions of interest were outlined on arterial and portal venous phase images and radiomics features were extracted to establish an arterio-portal radiomics model.Independent clinical risk factors associated with postoperative recurrence were explored by univariate and multivariate Cox analysis,then clinical model was established.A combined radiomics-clinical model was established by combining clinical independent risk factors and radiomics features.The area under the curve,specificity,sensitivity,net reclassification improvement and integrated discrimination improvement were used to assess the discrimination of all models.The calibration curve assessed the calibration of the model and decision curve analysis assessed the clinical utility of the model.Validation was performed by validation cohort data.Results The Rad-A5V5-clinical model had the best predictive performance for postoperative recurrence of HCC,the area under the curve,specificity and sensitivity of the validation cohort were 0.743(95%CI 0.640-0.846),0.647 and 0.717,respectively.The results of net reclassification improvement and integrated discrimination improvement showed that compared with clinical model and radiomics model,the prediction ability of Rad-A5V5-clinical model was improved the best one.The calibration curves showed that the predicted values of the Rad-A5V5-clinical model conformed the most favorably to the true values.The results of the decision curve analysis curve analyses showed that,among all models,the Rad-A5V5-clinical model would obtain the largest net benefit within a certain threshold range.Conclusion The predictive efficacy for post-tumor resection recurrence in HCC is significantly improved by incorporating tumor-peritumor radiomics features along with clinically independent risk factors.This finding offers a crucial reference point for identifying at-risk patients and tailoring individualized treatment plans.

Objective:To explore the mechanism of long non-coding RNA(lncRNA)HOXA transcript at the distal tip(HOT-TIP)in promoting the proliferation,migration and invasion of oral cancer cells via the mitogen activated protein kinase/extracellu-lar regulated protein kinase(MAPK/ERK)pathway.Methods:Human oral cancer KB cells were cultured in vitro and divided into control(without any treatment),pcDNA(transfected with pcDNA-NC,A group),pcDNA-HOTTIP(transfected with pcDNA-HOT-TIP,B group),MAPK/ERK pathway inhibitor PD98059(PD98059 group,50 μmol/L PD98059,C group)and pcDNA-HOTTIP+PD98059 groups(transfected with pcDNA-HOTTIP+50 μmol/L PD98059,D group).qRT-PCR was applied to detect HOTTIP mRNA expression,scratch test was applied to detect KB cell migration,Transwell assay was applied to detect cell invasion,flow cytometry was applied to detect cell apoptosis,CCK-8 was used to detect cell proliferation,Western blot was applied to detect the MAPK/ERK signaling pathway and epithelial mesenchymal transition(EMT)related protein expression levels in KB cells.Results:Compared with the control group,the KB cell scratch healing rate,cell invasion number,A450 value,p-MEK1/2,p-ERK1/2,and N-cadherin expression in pcDNA-HOTTIP group increased,the apoptosis rate and E-cadherin expression reduced(P＜0.05);scratch healing rate,cell invasion number,A450 value,p-MEK1/2,p-ERK1/2,and N-cadherin expression in PD98059 group reduced,the apoptosis rate and E-cadherin expression increased(P＜0.05).PD98059 weakened the role of HOT-TIP in promoting proliferation,migration and invasion of KB cells.Conclusion:LncRNA HOTTIP promotes proliferation,migra-tion,and invasion of KB cells by activating the MAPK/ERK pathway.

OBJECTIVE To explore the characteristics and influential factors of pharmaceutical clinic service demands， providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted， and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services， while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender， age， educational attainment， and economic burdens， to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%， yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware （P＜0.001）. The demand for pharmaceutical clinic services exhibited a hierarchical characteristic： twelve items were identified as attractive attributes （e. g.， providing suggestions for more affordable treatment options， offering online consultation services， etc.）， five items as expected attributes （e.g.， having a good attitude and being able to patiently answer your questions， etc.）， three items as must-have attributes （e.g.， providing guidance on medication dosage and usage， providing guidance on medication precautions， etc.）， five items as indifferent attributes （e.g.， providing treatment plan recommendations based on the patient’s condition）. There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients （P＜0.001）； patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above （P＝0.016）； those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above （P＝0.011）； patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” （P＝0.002）. CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low； however， those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover， the study also revealed that factors such as gender， age， educational level， and economic burdens exert significant influences on patients’ service demands.

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Objective:To explore the mechanism of long non-coding RNA(lncRNA)HOXA transcript at the distal tip(HOT-TIP)in promoting the proliferation,migration and invasion of oral cancer cells via the mitogen activated protein kinase/extracellu-lar regulated protein kinase(MAPK/ERK)pathway.Methods:Human oral cancer KB cells were cultured in vitro and divided into control(without any treatment),pcDNA(transfected with pcDNA-NC,A group),pcDNA-HOTTIP(transfected with pcDNA-HOT-TIP,B group),MAPK/ERK pathway inhibitor PD98059(PD98059 group,50 μmol/L PD98059,C group)and pcDNA-HOTTIP+PD98059 groups(transfected with pcDNA-HOTTIP+50 μmol/L PD98059,D group).qRT-PCR was applied to detect HOTTIP mRNA expression,scratch test was applied to detect KB cell migration,Transwell assay was applied to detect cell invasion,flow cytometry was applied to detect cell apoptosis,CCK-8 was used to detect cell proliferation,Western blot was applied to detect the MAPK/ERK signaling pathway and epithelial mesenchymal transition(EMT)related protein expression levels in KB cells.Results:Compared with the control group,the KB cell scratch healing rate,cell invasion number,A450 value,p-MEK1/2,p-ERK1/2,and N-cadherin expression in pcDNA-HOTTIP group increased,the apoptosis rate and E-cadherin expression reduced(P＜0.05);scratch healing rate,cell invasion number,A450 value,p-MEK1/2,p-ERK1/2,and N-cadherin expression in PD98059 group reduced,the apoptosis rate and E-cadherin expression increased(P＜0.05).PD98059 weakened the role of HOT-TIP in promoting proliferation,migration and invasion of KB cells.Conclusion:LncRNA HOTTIP promotes proliferation,migra-tion,and invasion of KB cells by activating the MAPK/ERK pathway.

Objective:To investigate the correlation between lung ultrasound score(LUS)and oxygenation index(OI),and between it and the ratio of arterial oxygen partial pressure(PaO2)to fraction of inspired oxygen(PaO2/FiO2)in patients with acute respiratory distress syndrome(ARDS)in intensive care unit(ICU).Methods:The documents of 168 ARDS patients who admitted to ICU of People's Hospital of Ningxia Hui Autonomous Region from June 2023 to June 2024 were retrospectively selected.According to the patients'prognosis,they were divided into survival group(114 cases)and death group(54 cases).The clinical documents,laboratory indexes including PaO2/FiO2 and LUS results of patients in the surviving group and the death group were collected and compared,and the effects of LUS and PaO2/FiO2 on the prognosis of ARDS patients were analyzed by logistic regression.The predictive value of LUS and PaO2/FiO2 on the prognosis of ARDS patients was analyzed by the receiver operating characteristics(ROC)curve.Finally,the correlation between LUS and PaO2/FiO2 of patients was analyzed by using Pearson analysis.Results:There were significant differences in age,Acute Physiology and Chronic Health Evaluation II(APACHE II)score,mean arterial pressure(MAP),ratio of E peak to A peak of mitral valve velocity,positive end expiratory pressure(PEEP),tidal volume(VT),PaO2/FiO2,and LUS between the death group and the survival group,and the differences were statistically significant(t=8.456,2.073,6.780,3.361,3.204,2.925,7.801,12.210,P<0.05),respectively,in which the PaO2/FiO2 level[(180.67±25.61)mmHg]of the death group was significantly lower than that[(217.87±34.70)mmHg]of the survival group,and the LUS score[(21.00±3.97)point]was higher than that[(13.63±3.50)point]of the survival group.The PaO2/FiO2 was a protective factor for the prognosis of ARDS patients(OR=0.943,P<0.05),while LUS was a risk factor(OR=2.729,P<0.05).The area under curve(AUC)values of PaO2/FiO2 and LUS were respectively 0.802 and 0.919 in predicting the prognosis of ARDS patients.LUS and PaO2/FiO2 levels showed a negative correlation(R=-0.707,P<0.001).Conclusion:Both LUS and PaO2/FiO2 have better predictive effect for the prognosis of ARDS patients,and LUS can be used in the early prediction for the oxygenation status and the assessment about prognosis of ARDS patients,and the subsequent guideline for formulating therapeutic measures in clinical practice.