As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

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: 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 investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

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*

Objective:To study the influencing factors of postpartum post-traumatic stress disorder(PTSD)in pregnant women in the third trimester of pregnancy based on propensity score matching(PSM).Methods:A retrospective analysis was conducted on clinical data of 220 pregnant women in the third trimester who visited our hospital from October 2022 to October 2024,they were divided into PTSD group(n=52)and non-PTSD group(n=168)based on whether PTSD occurred.PSM was adopted to match the age,body mass index(BMI),educational level,average monthly income per capita,natural conception,premature birth,pregnancy complications,first delivery,insomnia,the progress of labor,parenting methods,infant health status and postpartum depression of the two groups at a 1∶1 ratio.After matching,Logistic regression was used to analyze the influencing factors of postpartum PTSD in pregnant women in the third trimester of pregnancy.Result:When comparing the educational level,natural conception,premature birth,pregnancy complications,progress of labor and postpartum depression of the two groups before matching,the differences were statistically significant(P＜0.05).When comparing the comparisons of educational level,natural conception,premature birth,pregnancy complications,progress of labor and postpartum depression of the two groups after matching,the differences were statistically significant(P＜0.05).Logistic regression analysis showed that junior high school education level or below,non-natural conception,premature birth,pregnancy complications,abnormal labor process and postpartum depression were risk factors for PTSD(P＜0.05).Conclusion:Based on PCM,it was found that low educational level,non-natural conception,premature birth,pregnancy complications,abnormal labor process and postpartum depression are risk factors for postpartum PTSD in pregnant women in the third trimester of pregnancy,and reasonable preventive interventions could be taken as early as possible in pregnant women with high risk of PTSD.

Objective:To study the influencing factors of postpartum post-traumatic stress disorder(PTSD)in pregnant women in the third trimester of pregnancy based on propensity score matching(PSM).Methods:A retrospective analysis was conducted on clinical data of 220 pregnant women in the third trimester who visited our hospital from October 2022 to October 2024,they were divided into PTSD group(n=52)and non-PTSD group(n=168)based on whether PTSD occurred.PSM was adopted to match the age,body mass index(BMI),educational level,average monthly income per capita,natural conception,premature birth,pregnancy complications,first delivery,insomnia,the progress of labor,parenting methods,infant health status and postpartum depression of the two groups at a 1∶1 ratio.After matching,Logistic regression was used to analyze the influencing factors of postpartum PTSD in pregnant women in the third trimester of pregnancy.Result:When comparing the educational level,natural conception,premature birth,pregnancy complications,progress of labor and postpartum depression of the two groups before matching,the differences were statistically significant(P＜0.05).When comparing the comparisons of educational level,natural conception,premature birth,pregnancy complications,progress of labor and postpartum depression of the two groups after matching,the differences were statistically significant(P＜0.05).Logistic regression analysis showed that junior high school education level or below,non-natural conception,premature birth,pregnancy complications,abnormal labor process and postpartum depression were risk factors for PTSD(P＜0.05).Conclusion:Based on PCM,it was found that low educational level,non-natural conception,premature birth,pregnancy complications,abnormal labor process and postpartum depression are risk factors for postpartum PTSD in pregnant women in the third trimester of pregnancy,and reasonable preventive interventions could be taken as early as possible in pregnant women with high risk of PTSD.

As a long-standing research focus in electroanalytic chemistry,electrochemical biosensors have attracted immense interest in detection of biological targets such as small molecules,proteins,enzymes,nucleic acids,exosomes,circulating tumor cells (CTCs),bacteria,and viruses. etc. The highly sensitive and selective electrochemical detection of biological targets relies on the use of the specific biorecognition elements (BREs) and efficient signal amplification strategies. In this review,the typically used BREs and amplification strategies in electrochemical biosensing were summarized. On the basis of the interactions between BREs and targets,the enzyme/substrate-based and receptor/ligand-based electrochemical biosensors were first introduced,focusing on the BREs used in the electrochemical detection of nucleic acid targets and non-nucleic acid targets. Then,the representative use of various isothermal nucleic acid amplification technologies,catalytic reactions,functionalized nanocarriers,and polymer materials in amplified electrochemical detection of biological targets were introduced. The challenges with respect to the practical use of electrochemical biosensors and the prospect of electrochemical biosensing were discussed.

Polysaccharides are the important material basis of traditional Chinese medicine（TCM）， and have various pharmacological activities such as immunomodulation， antitumor and anti-aging. Due to the large molecular weight of TCM polysaccharides， their structural analysis and oral absorption mechanism are facing technical challenges， and the current research on their structure-activity relationships has made some breakthroughs， while the research on their oral absorption mechanisms is relatively slow. In-depth study of the oral absorption mechanism of TCM polysaccharides is not only crucial for the interpretation of their action pathways and efficacy in vivo， but also helpful for the interpretation of their pharmacological effects， rational clinical applications and the discovery of new targets. In recent years， the application of fluorescent labeling and isotopic labeling methods has provided new technical means for the oral absorption studies of polysaccharides， which has promoted the development of oral absorption studies of TCM polysaccharides. In this paper， we reviewed the oral absorption pathways and labeling techniques of TCM polysaccharides， and concluded that they can be absorbed orally through transmembrane， cellular bypass， and M-cell-mediated transport， of which transmembrane pathway is the main absorption pathway， and summarized the labeling reactions of four fluorescent labeling and isotopic labeling methods with TCM polysaccharides， which can provide references for evaluating the absorption pathways of TCM polysaccharides， screening active TCM polysaccharides， establishing pharmacodynamic models and comprehensively elucidating the mechanism of TCM polysaccharides.