Objective To investigate the relationship between serum Rho-associated coiled coil containing protein kinase 2(ROCK2),syndecan-1(SDC-1),Apelin-13 and renal function and prognosis in patients with diabetes nephropathy.Methods From November 2019 to November 2021,153 patients with diabetic nephrop-athy admitted to the hospital were selected as the study group,and 153 patients with simple diabetes were se-lected as the simple diabetes group.Another 153 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group.The levels of serum ROCK2,SDC-1 and Apelin-13 were determined by enzyme-linked immunosorbent assay.Pearson correlation analysis was used to analyze the correlations between the levels of serum ROCK2,SDC-1,and Apelin-13 and the clinical data of pa-tients with urinary nephropathy.Univariate and multivariate Logistic regression analyses were conducted to analyze the influencing factors of poor prognosis in patients with diabetic nephropathy.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of serum ROCK2,SDC-1 and Apelin-13 for poor prognosis of patients with diabetes nephropathy.Results Compared with the healthy control group,the levels of serum ROCK2 and SDC-1 in the simple diabetes group and the study group increased,the level of Apelin-13 decreased,the estimated glomerular filtration rate(eGFR)decreased,and the ratio of urinary albu-min to creatinine(UACR)increased,and the differences were statistically significant(P＜0.05).The levels of serum ROCK2,SDC-1,Apelin-13 and UACR in the study group were higher than those in the simple diabe-tes group,while eGFR was lower than that in the simple diabetes group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis indicated that the levels of serum ROCK2,SDC-1,and Apelin-13 in the study group were negatively correlated with eGFR(P＜0.05),and positively correlated with renal disease stage,creatinine,24-hour proteinuria,and UACR index(P＜0.05).Compared with the good prognosis group,the levels of serum ROCK2,DCC-1,Apelin-13 and UACR in the poor prognosis group in-creased(P＜0.05),and eGFR decreased(P＜0.05).Univariate and multivariate Logistic regression analyses indicated that the levels of serum ROCK2,SDC-1,and Apelin-13 were all influencing factors for the prognosis of patients(P＜0.05).ROC curve analysis indicated that the area under the curve(AUC)for the combined prediction of poor prognosis in patients by serum ROCK2,DCC-1,and Apelin-13 levels was significantly grea-ter than that by ROCK2(Z=2.854,P=0.004)and DCC-1(Z=2.426,P=0.015)and Apelin-13(Z=2.172,P=0.030)were predicted separately.Conclusion The serum ROCK2,DCC-1 and Apelin-13 levels in patients with diabetic nephropathy increase and are related to renal function.The combination of the three has a relatively high predictive efficacy for the prognosis of patients.

Background and aims:Studies indicate that the gut microbiota and its metabolites are involved in the progression of cardiovascular diseases,and enterohepatic circulation plays an important role in this progression.This study aims to identify potential probiotics for the treatment of unstable angina(UA)and elucidate their mechanisms of action.Methods:Initially,the gut microbiota from patients with UA and control was analyzed.To directly assess the effects of Bifidobacterium supplementation,10 patients with UA were enrolled and administered Bifidobacterium(630 mg per intake twice a day for 1 month).The fecal metagenome,serum trimethyl-amine N-oxide(TMAO)levels,and other laboratory parameters were evaluated before and after Bifido-bacterium supplementation.Results:After supplementing with Bifidobacterium for 1 month,there were statistically significant dif-ferences(P＜0.05)in TMAO,aspartate aminotransferase,total cholesterol,and low-density lipoprotein compared to before.Additionally,the abundance of Bifidobacterium longum increased significantly,although the overall abundance of Bifidobacterium did not reach statistical significance.The gut micro-biota,metabolites,and gut-liver axis are involved in the progression of UA,and potential mechanisms should be further studied.Conclusions:Metagenomic analysis demonstrated a reduced abundance of Bifidobacterium in patients with UA.Supplementation with Bifidobacterium restored gut dysbiosis and decreased circulating TMAO levels in patients with UA.This study provides evidence that Bifidobacterium may exert cardiovascular-protective effects through the gut-liver-heart axis.

Spinal cord injury(SCI)is a structural and functional disruption of the spinal cord caused by various factors,leading to neurological dysfunction.As a common central nervous system disorder in clinical practice,SCI poses significant risks to human life and health.Its pathological mechanism is exceedingly complex,involving multiple pathological processes.Given the irreversibility of primary injury,targeting secondary injury has gradually become the main direction for the clinical treatment of SCI in recent years.Recent studies have highlighted the crucial role of blood-spinal cord barrier damage and microvascular dysfunction in the progression of secondary injury following SCI.Therefore,investigating the pathological mechanisms of microcirculation and exploring targeted therapies could provide valuable insights for clinical SCI treatment.This paper aims to provide an objective review of the role of microcirculation in SCI,identify the critical regulators of microvascular function,and summarize strategies for treating SCI by targeting microcirculation.The findings of this study may offer novel references for the clinical management of SCI.

Spinal cord injury(SCI)is a central nervous system disease with high morbidity and disability rates,bringing serious economic and psychological burdens to families and society worldwide.AMP-activated protein kinase(AMPK)is an important sensor in the energy metabolism process in living organisms,which plays a central role in maintaining energy balance.It is currently considered a key target for the prevention and treatment of multiple diseases.Studies have shown that AMPK signaling can regulate autophagy,neuroinflammation,oxidative stress,mitochondrial function and other processes after SCI,thus affecting the pathological process of SCI.This review summarizes the research progress on AMPK signaling pathway involved in the regulation of SCI,in order to provide new ideas for the treatment and drug development of SCI.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Objective To investigate the diagnostic value of serum bromodomain-containing pro-tein 4(BRD4)combined with gastrin-17(G-17)in Helicobacter pylori(Hp)-positive early gastric cancer.Methods A total of 88 patients with Hp-positive early gastric cancer admitted to our hospital from September 2021 to September 2023 were selected as early gastric cancer group.Meanwhile,92 patients with Hp-positive precancerous lesions and 80 patients with Hp-positive gastritis admitted dur-ing the same period were selected as precancerous lesion group and gastritis group,respectively.En-zyme-linked immunosorbent assay(ELISA)was used to detect the serum levels of BRD4 and G-17.Multivariate logistic regression analysis was performed to screen the influencing factors of Hp-positive early gastric cancer.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic value of serum BRD4 and G-17 in Hp-positive early gastric cancer.Results Compared with the gastritis group,the levels of BRD4 and G-17 in the precancerous lesion group and early gastric cancer group were significantly increased(P＜0.05).Furthermore,compared with the precancerous le-sion group,the levels of BRD4 and G-17 in the early gastric cancer group were also significantly elevated(P＜0.05).The proportion of patients with a family history of gastric cancer,those who preferred hot food,cold food,or high-salt food,as well as the levels of PG Ⅱ,BRD4,and G-17 were signifi-cantly higher in the early gastric cancer group than in the non-gastric cancer group,while the level of pepsinogen(PG)Ⅰ was significantly lower(P＜0.05).Logistic regression analysis revealed that preference for hot food,high-salt food,PG Ⅱ,BRD4,G-17,and PG Ⅰ were all influencing factors for Hp-positive early gastric cancer(P＜0.05).The area under the curve(AUC)values for serum BRD4,G-17,and their combination in diagnosing Hp-positive early gastric cancer were 0.793,0.830,and 0.912,respectively.The diagnostic efficacy of the combined detection was superior to that of single detection(P＜0.05).Conclusion The serum levels of BRD4 and G-17 are elevated in patients with Hp-positive early gastric cancer,and both exhibit certain diagnostic value for Hp-positive early gastric cancer,suggesting their potential as serum biomarkers for the diagnosis of Hp-positive early gastric cancer.

Objective To investigate the effect of Tan Ⅰ on SA-AKI in rats by mediating Wnt/β-catenin signaling pathway.Methods Sprague-Dawley rats were randomly divided into the following groups(n=8 per group,including 2 reserve animals per group):Sham,SA-AKI,SA-AKI+5 mg/kg Tan I,SA-AKI+10 mg/kg Tan I,SA-AKI+15 mg/kg Tan I(SA-AKI+Tan I),SA-AKI+salinomycin sodium(SS,Wnt signal inhibitor,SA-AKI+SS),SA-AKI+SS+Tan I,SA-AKI+laduviglusib(LG,Wnt signal activator,SA-AKI+LG),and SA-AKI+LG+Tan I.Rat SA-AKI model was induced by cecal ligation and puncture(CLP),with Tan I,SS,and LG administered via intraperitoneal injection.Hematoxylin-eosin and TUNEL staining were used to observe renal tissue pathological damage.Enzyme-linked immunosorbent assay was used to detect serum concentrations of neutrophil gelatinase-associated lipocalin(NGAL),IL-1β,IL-8,IL-6,and TNF-α.Creatinine(Cre)and blood urea nitrogen(BUN)kit were used to detect serum Cre and BUN concentrations.Western blot and immunofluorescence staining were used to detect the expression and fluorescence intensity of Wnt1,GSK3β,and β-catenin.Results Administration of Tan I at doses of 10 mg/kg and 15 mg/kg significantly attenuated renal injury in rats with SA-AKI(P<0.05),suppressed the levels of SA-AKI biomarkers NGAL,Cre,and BUN and pro-inflammatory cytokines(P<0.05),reduced apoptosis,and downregulated Wnt1 and GSK3β while upregulating β-catenin expression(P<0.05).Although Tan I at 5 mg/kg exhibited a modest protective effect against SA-AKI in rats,no statistically significant difference was observed compared to the sham group(P>0.05).SS weakened CLP-induced kidney injury and the production of inflammatory cytokines in rats(P<0.05),and LG further aggravated CLP-induced kidney injury in rats(P<0.05).Tan Ⅰ reversed the promoting effect of LG on kidney injury in SA-AKI rats(P<0.05).Conclusion Tan Ⅰ provides a protective effect on CLP-induced SA-AKI rat by inhibiting Wnt/β-catenin signaling pathway.

Colorectal cancer(CRC)is a common malignancy of the digestive system,with increasing morbidity and mortality worldwide.The standard treatment for CRC has,in the past,been surgery,chemotherapy,and radiotherapy.However,these treatments have significant side effects and are particularly challenging for patients with advanced metastatic CRC(mCRC).Therefore,it is crucial to explore alternative and more effective treatments.In recent years,with the development of molecular technology,numerous biomarkers have been identified,and targeted therapy and immunotherapy have achieved surprisingly positive results in the treatment of mCRC.Patients receiving targeted ther-apy and immunotherapy have an improved prognosis and quality of life.On this basis,this article reviews the latest research progress in tar-geted therapy and immunotherapy for mCRC,providing a reference for precision treatment of mCRC.

Fear of disease progression(FoP)is a common psychological state among patients with coronary heart dis-ease(CHD),which exists throughout the course of disease and seriously affects the prognosis.High level of FoP not only harms the mental health of patients but also do not benefit their rehabilitation after discharge.This concept was first proposed by foreign researchers studying the psychological state of cancer patients.In recent years,there have been numerous studies on the influencing factors and qualitative aspects of FoP in CHD patients,while related inter-vention studies remain few.This paper reviews the concept,scales and related influencing factors of FoP,providing ideas for medical staff to provide targeted interventions for CHD patients.

″Boundarics in biomedicine″(or″Biomedical boundarics″)is an emerging frontier interdisciplinary subject that focuses on addressing key scientific issues related to the formation,identification,and evolution of biological boundaries within living organisms.In this field,the study of tumor boundaries is of particular importance.Imaging tumor boundaries not only helps to reveal the molecular mechanisms of tumor boundary evolution and interaction with the microenvironment,tumor invasion and metastasis,but is also crucial for clinical tumor diagnosis,treatment decision-making,efficacy monitoring and prognosis evaluation.Molecular probes,as functional substances that enhance imaging signals,play a crucial role in tumor boundary recognition.In this article,the basic concepts and research significance of boundarics in biomedicine and tumor boundarics in biomedicine were summarized firstly.Then a comprehensive review of the research progress in tumor boundary imaging molecular probes was provided,covering areas such as magnetic imaging,optical imaging,acoustic imaging,nuclear imaging,and multimodal imaging.The strategies to regulate the sensitivity,specificity,and safety of molecular probes through chemical structure modifications,conjugation with targeting ligands,and tumor microenvironment-responsive designs were emphasized.Finally,the research trends of molecular probes for tumor boundary imaging were analyzed,and the challenges faced in this field and the future research directions were discussed.