BACKGROUND:The long-term patency rate of synthetic blood vessels remains a significant challenge that requires urgent attention.Enhancing the anticoagulant performance of small-caliber artificial blood vessels is crucial in ensuring their long-term efficacy.OBJECTIVE:To investigate the anticoagulation activity of polycaprolactone/low molecular weight fucoidan nanofibers with shell core structure and determine the effect on the activity of human umbilical vein endothelial cells.METHODS:Polycaprolactone nanofiber membranes and polycaprolactone/low molecular weight fucoidan nanofiber membranes with polycaprolactone as shell layer and low molecular weight fucoidan as core layer were prepared by emulsion electrospinning method(the mass ratio of low molecular weight fucoidan to polycaprolactone was 10％,25％,40％,and 55％,respectively).The morphology and structure of the fibers were characterized by scanning electron microscopy,fluorescence microscopy,and infrared spectroscopy.The mechanical strength of the fiber membranes was detected by tensile test.The loading rate and sustained release rate of low molecular weight fucoidan in the nanofibers were detected by 1,9-dimethylmethylene blue dye.The anticoagulant properties of the fiber membranes were verified by hemolysis test,dynamic coagulation test,plasma recalcification test,and platelet adhesion test.The five fiber membranes were co-cultured with human umbilical vein endothelial cells.The cell proliferation was detected by CCK-8 assay and the cell morphology was observed by fluorescence microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the surface of polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane was smooth,the fiber diameter was uniform,and there was no obvious beaded structure.With the increase of low molecular weight brown algae polysaccharide content in the fiber membrane,the diameter of the fiber membrane increased and the maximum tensile stress decreased,but it still met the mechanical properties requirements of small-caliber artificial blood vessels.Fluorescence images and infrared spectra confirmed that low molecular weight brown algae polysaccharide was successfully loaded into polycaprolactone nanofiber membrane,and the low molecular weight brown algae polysaccharide loaded in each group of fiber membranes was released suddenly within 12 hours and released at a relatively low rate after 48 hours.(2)Compared with polycaprolactone nanofiber membrane,polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane had better anticoagulant activity,among which the group with a mass ratio of low molecular weight brown algae polysaccharide to polycaprolactone of 25％had the best anticoagulant effect.All five fiber membranes supported the growth and proliferation of human umbilical vein endothelial cells without affecting cell morphology and had no obvious cytotoxicity.(3)The results show that the polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane has good anticoagulant function,blood compatibility,and cell compatibility.

BACKGROUND:The long-term patency rate of synthetic blood vessels remains a significant challenge that requires urgent attention.Enhancing the anticoagulant performance of small-caliber artificial blood vessels is crucial in ensuring their long-term efficacy.OBJECTIVE:To investigate the anticoagulation activity of polycaprolactone/low molecular weight fucoidan nanofibers with shell core structure and determine the effect on the activity of human umbilical vein endothelial cells.METHODS:Polycaprolactone nanofiber membranes and polycaprolactone/low molecular weight fucoidan nanofiber membranes with polycaprolactone as shell layer and low molecular weight fucoidan as core layer were prepared by emulsion electrospinning method(the mass ratio of low molecular weight fucoidan to polycaprolactone was 10％,25％,40％,and 55％,respectively).The morphology and structure of the fibers were characterized by scanning electron microscopy,fluorescence microscopy,and infrared spectroscopy.The mechanical strength of the fiber membranes was detected by tensile test.The loading rate and sustained release rate of low molecular weight fucoidan in the nanofibers were detected by 1,9-dimethylmethylene blue dye.The anticoagulant properties of the fiber membranes were verified by hemolysis test,dynamic coagulation test,plasma recalcification test,and platelet adhesion test.The five fiber membranes were co-cultured with human umbilical vein endothelial cells.The cell proliferation was detected by CCK-8 assay and the cell morphology was observed by fluorescence microscopy.RESULTS AND CONCLUSION:(1)Scanning electron microscope showed that the surface of polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane was smooth,the fiber diameter was uniform,and there was no obvious beaded structure.With the increase of low molecular weight brown algae polysaccharide content in the fiber membrane,the diameter of the fiber membrane increased and the maximum tensile stress decreased,but it still met the mechanical properties requirements of small-caliber artificial blood vessels.Fluorescence images and infrared spectra confirmed that low molecular weight brown algae polysaccharide was successfully loaded into polycaprolactone nanofiber membrane,and the low molecular weight brown algae polysaccharide loaded in each group of fiber membranes was released suddenly within 12 hours and released at a relatively low rate after 48 hours.(2)Compared with polycaprolactone nanofiber membrane,polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane had better anticoagulant activity,among which the group with a mass ratio of low molecular weight brown algae polysaccharide to polycaprolactone of 25％had the best anticoagulant effect.All five fiber membranes supported the growth and proliferation of human umbilical vein endothelial cells without affecting cell morphology and had no obvious cytotoxicity.(3)The results show that the polycaprolactone/low molecular weight brown algae polysaccharide nanofiber membrane has good anticoagulant function,blood compatibility,and cell compatibility.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective To explore the application of linaclotide combined with compound polyethylene glycol electrolyte powder(PEG)in bowel preparation for colonoscopy of patients with chronic constipation.Methods A toltal of 190 patients with chronic constipation who underwent electronic colonoscopy in Beijing NO.6 Hospital from January to October 2023 were selected as the objects.The patients were divide into linaclotide group(n=63),3L PEG group(n=64),and 4L PEG group(n=63)by random number table method.The application effects of three groups were compared.Results Boston bowel preparation scale score was higher than 3L PEG and 4L PEG groups,there were significant difference among groups(P＜0.05).The qualified rate of patients in linaclotide group was better than that of 3L PEG group and 4L PEG group,and the qualified rate of patients in 4L PEG group was better than that of 3L PEG group,there were significant difference among groups(P＜0.05).Conclusion Linaclotide combined with PEG can not only improve the intestinal cleaning quality of patients with constipation,but also do not increase the adverse reactions of patients.

Under the influence of long-term space flights and the confined space environment,it is very easy to induce space depression syndrome,mainly manifested as decreased emotional stability,sleep disorders,mental fatigue,etc.,which seriously affect the living conditions and working abilities of astronauts.The current treatment methods mainly focus on psychological support and drug intervention.Acupuncture has a good effect in treating depression.Therefore,starting from the TCM pathogenesis and modern medical pathogenesis of aerospace depression syndrome,we conducted literature retrieval from databases such as the Chinese Medical Classic,China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of science.For the included literature,we adopted the stratified evidence scoring method and combined the TCM mechanism and modern medical mechanism of the effect of acupuncture.A prescription for acupuncture points was constructed to provide a basis for selecting acupuncture points for the prevention of aerospace depression syndrome through acupuncture.

Objective To study the dynamic regulatory role of early growth response 4(EGR4)in mouse neurodevelopment.Methods Data on single-cell chromatin accessibility(single-cell assay for transposase-accessible chromatin by sequencing,scATAC-seq)and transcriptome(single-cell RNA sequencing,scRNA-seq)from seven key stages spanning from the embryonic period to adulthood was collected and analyzed.The transcription factor binding site network was inferred,a quantitative analysis from a temporal perspective was conducted,its functional modules were parsed,and the results were visualized.Results egr4 was significantly highly expressed from the late embryonic stage to adulthood,and specifically activated during the maturation of inhibitory neurons[parvalbumin(PV)and somatostatin(SST)subtypes].Moreover,its transcription was not directly regulated by changes in chromatin accessibility.Temporal network analysis indicated that EGR4 became a regulatory hub in the late embryonic stage and drove neuron differentiation and subtype specification.Functional enrichment analysis showed that EGR4 regulated the"cell differentiation"pathway through dynamic interacting factors,and there were subtype-specific interaction modules in PV/SST neurons respectively.Conclusion EGR4 can participate in the late-stage maturation of cortical neurons through a stage-specific regulatory network.This study provides a new perspective on mechanisms underlying the temporal logic of neural development.

Objective:To investigate the role of the angiopoietin (Ang)/tyrosine kinase receptor 2 (Tie2) pathway in mediating histone-induced coagulation activation in mice with acute lung injury, and the protective mechanism of unfractionated heparin (UFH).Methods:Twenty-four mice were randomly divided into three groups ( n=8 per group): Control group, Histone group, and Histone + UFH group using the random number table method. The Histone group and Histone + UFH group were administered 50 mg/kg histone via the tail vein. One hour later, UFH was given at a dosage of 400 U/kg by the same way. The Control group was administered an equivalent volume of sterile saline solution. Four hours after modeling, tissue samples were collected. HE staining was performed to observe the pathology of lung tissue. Lung lobe wet and dry weights were measured to assess the degree of pulmonary edema. Immunohistochemistry was used to observe the expression of fibrinogen (FIB) in lung tissue. ELISA was used to detect the levels of thrombin-antithrombin complex (TAT), plasminogen activator inhibitor type-1 (PAI-1), and D-dimer (D-D) in plasma. The qRT-PCR was used to measure the mRNA expression levels of tissue factor (TF), FIB, PAI-1, angiopoietin (Ang)-1, Ang-2, and Tie2 in lung tissue. Western blot was used to measure the protein expression levels of TF, FIB, Ang-1, Ang-2, and pTie2 in lung tissue. Results:The HE staining results revealed that, compared to the Control group, the Histone group exhibited thickened alveolar walls, significant neutrophil infiltration, and alveolar congestion with edema, indicating histone-induced ALI ( P<0.001). In contrast, the Histone + UFH group exhibited milder lung injury ( P<0.001), suggesting that UFH mitigated the lung damage induced by histones. The lung wet/dry weight ratio and lung water content percentage were significantly higher in the Histone group than in the Control group ( P<0.001), while UFH reduced the severity of pulmonary edema ( P<0.01). Immunohistochemistry revealed intravascular thrombus formation and fibrin deposition in the Histone group, which were reduced by UFH. ELISA results showed significantly elevated levels of TAT, PAI-1, and D-D in the Histone group ( P<0.001), and UFH decreased the levels of these parameters stimulated by histone ( P<0.05). The qRT-PCR showed increased mRNA expression of TF, FIB, PAI-1, and Ang-2, and decreased expression of Ang-1 and Tie2 in lung tissues in the Histone group, while UFH mitigated the effects of histones on mRNA expression of these parameters. Western blot analysis indicated increased protein expression of TF, FIB, and Ang-2 ( P<0.01), and decreased expression of Ang-1 and Tie2 in lung tissues in the Histone group ( P<0.01), and UFH reduced the impact of histones on the protein expression of these parameters ( P<0.05). Conclusions:Histones can cause lung injury, pulmonary edema, and coagulation activation in mice lung tissue. UFH can effectively alleviate histone induced lung injury, and coagulation activation in by histones via the Ang/Tie2 signaling pathway.

Objective:To investigate the temporal expression of Growth Differentiation Factor-15 (GDF15) in the serum of patients with Acute Coronary Syndrome (ACS) and explore the clinical significance of GDF15 in protecting cardiomyocytes in ACS.Methods:A retrospective study was conducted on 289 ACS patients admitted to the emergency departments from February to October 2023. Data on gender, age, troponin T (TnT), creatine kinase isoenzyme (CK-MB), GDF15, and B-type natriuretic peptide (BNP) within 30 minutes of admission were recorded. Differences in these indicators among different groups were compared. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the diagnostic value of GDF15, TnT, and BNP for ACS. Among the patients, 15 exhibited a temporal expression pattern of GDF15, and their blood samples were re-measured using a GDF15 fluorescent quantitative immunochromatographic assay kit. Fifteen patients without temporal expression were randomly selected as controls, and their samples were also re-measured to exclude detection errors. Fifteen patients with temporal expression were included in the temporal expression group, and 15 without temporal expression were included in the non-temporal expression group. Laboratory indicators such as fasting blood glucose, glycated hemoglobin, triglycerides, creatinine, and uric acid were compared between the groups. Additionally, patient age, gender, body mass index (BMI), coronary angiography results, echocardiography, Gensini score, left ventricular ejection fraction (LVEF), and GRACE risk score were recorded to assess their correlation with GDF15 temporal expression. Statistical analysis was performed using SPSS 27 software, with continuous data expressed as mean ± standard deviation (Mean ± SD) and compared using t-tests and χ2 tests. Results:The overall trend in ACS patients showed a higher proportion of males than females (73.36% vs. 26.64%). The oldest group was the Unstable Angina (UA) group, with a mean age of (63.98 ± 15.19) years, while the youngest group was the non-ACS chest pain group, with a mean age of (54.29 ± 16.39) years. A higher proportion of patients in the UA, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) groups had a history of smoking. The combination of GDF15 and TnT showed high diagnostic value for ACS, with an area under the ROC curve (AUC) of 0.843, consistent with previous studies. Among all ACS patients, 15 exhibited a temporal expression pattern of GDF15, where GDF15 levels peaked at 4 hours, gradually decreased, and peaked again at 24 hours. Patients in the temporal expression group had higher LVEF and left ventricular end-systolic diameter compared to the non-temporal expression group. The Gensini score was lower in the temporal expression group, and the GRACE risk score was significantly lower in the temporal expression group (00.7±14.72) compared to the non-temporal expression group (116.1±23.46), with a statistically significant difference ( P = 0.0115). There were no significant differences in general characteristics (age, gender, BMI) or clinical biochemical indicators (fasting blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid) between the temporal and non-temporal expression groups ( P > 0.05). Conclusions:GDF15 demonstrates significant diagnostic and prognostic predictive value in ACS. Patients with temporally dynamic expression of serum GDF15 exhibit milder myocardial injury and a lower probability of mortality. These findings provide novel therapeutic targets and research directions for further exploring the role of GDF15 in ACS management.

ObjectiveTo understand the uncorrected visual acuity, spherical equivalent and hyperopia reserve of 6‒8-year-old primary school students in Jing’an District of Shanghai, and to provide a scientific basis for further myopia prevention and control. MethodsA total of 619 children aged between 6‒8 years old from three primary schools in Jing’an District were selected by cluster sampling method for uncorrected eye visual acuity examination and diopter examination after cycloplegia (mydriasis). ResultsThe mean uncorrected visual acuity of the619 students aged 6‒8 years old was (4.9±0.2), and the mean spherical equivalent was (0.84±1.11) D. The difference in uncorrected visual acuity was not statistically significant as the age increased (F=0.057, P=0.812), but the spherical equivalent decreased with the increase of age, showing a statistically significant difference (F=26.533, P<0.001). There was no statistically significant difference in uncorrected visual acuity(t=-1.614, P=0.107) and spherical equivalent (t=-1.675, P=0.094) between students of different genders. Finally, among the 619 students, 59.80% of them had abnormal uncorrected visual acuity, 34.90% had insufficient hyperopia reserve, and only 5.30% had sufficient hyperopia reserve. Besides, the proportion of abnormal uncorrected visual acuity in 7-year-old students was 67.50%, higher than that of students with other ages, and the difference was statistically significant (χ²_trend=29.729, P<0.001). While the difference in abnormal uncorrected visual acuity between students of different genders was not statistically significant (χ²=0.068, P=0.967). ConclusionThe deficiency of hyperopia reserve in 6‒8-year-old students in Jing’an District of Shanghai is serious. Attention should be paid to the visual acuity of school-aged children in lower grades, and intervention measures should be actively carried out to slow down the progression of myopia.

Objective To explore the clinical efficacy of dual plasma molecular adsorption(DPMAS)sequential plasma exchange(PE)artificial liver mode in the treatment of liver failure(LF).Methods Eighty-five patients with LF receiving the artificial liver treatment in the Affiliated Hospital of Zunyi Medical Univer-sity from January 2020 to December 2023 were selected as the study subjects and divided into the study group(n=52)and the control group(n=33)according to the different treatment modes.The study group conduc-ted DPMAS sequential PE treatment and the control group underwent the PE treatment.The liver function[total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum albumin(ALB),globulin(GLO),prealbumin(PAB)],Hb,coagulation function[platelet(PLT),plasminogen activity(PTA),international normalized ratio(INR),fibrinogen(FIB)]before treatment and at 24 h after treatment were compared between the two groups.Results Compared with before treatment,the levels of TBIL,ALT,AST,GLO and Hb after the first and second treatment in the two groups were decreased,ALB level in the control group and PAB level after the second time treatment was increased(P＜0.05).Compared with after the first treatment,the levels of TBIL,ALT and GLO after the second treatment in the two groups and the levels of AST and Hb in the study group were decreased,ALB level in the study group and PAB level in the two groups were increased(P＜0.05).Compared with before treatment,the levels of PLT and FIB after the first treatment in the two groups and INR level in the control group were decreased,PTA level in the control group was increased(P＜0.05).Compared with before treatment,the levels of PLT,INR and FIB after the second treatment in the two groups were decreased,PTA level was increased(P＜0.05).Compared with be-fore treatment,the levels of PLT,INR and FIB after the second treatment in the two groups were decreased,and PTA level was increased(P＜0.05).Compared with after the first treatment,PTA level after the second treatment in the study group was increased and INR level was decreased.Conclusion PE and DPMAS sequen-tial PE all could improve the liver function in the patients with LF,moreover the two times treatment has more significant effect.