BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

The traditional experimental teaching mode of forensic science and biological evidence is mostly confined to experimental operation, which is not capable of cultivating students' comprehensive quality and post competency. Therefore, it is urgent to seek an innovative teaching and training mode. At present, the experimental teaching of forensic science and biological evidence is dominated by teachers. There are some problems, such as insufficient training of students' scientific thinking and innovation ability, single teaching and evaluation model, and disconnection from the practical application. This paper proposes an experimental teaching design scheme of forensic science and biological evidence based on post competency training. The course is implanted in the framework of simulated cases, and the virtual simulation experiment platform and group discussion learning method are used to achieve a training model oriented by social needs and centered on students. In the preliminary study on the students who were trained in this mode of selected sections, we found that, compared with traditional teaching, the time for students to complete the prescribed experimental operation in this teaching mode was shortened by 4 minutes on average, and the average score of theoretical course test case analysis questions was increased by 1.5 points. In conclusion, the instructional design of the experiment teaching forensic science and biological evidence can effectively improve students' post-competency, and it deserves further exploration and application.

In recent years,the use of bioprosthetic mitral valves has been increasing,leading to a growing number of patients experiencing bioprosthesis degeneration,significantly impacting their quality of life.The high risk of reoperation has deprived many patients with mitral bioprosthesis degeneration of the opportunity for a second surgery.With the rapid development of interventional procedures in our country,transcatheter mitral valve-in-valve replacement is gradually being accepted by a large number of patients with bioprosthesis degeneration.We report a case of transcatheter mitral valve-in-valve replacement via transseptal puncture.The surgical plan was carefully formulated based on preoperative CT evaluation,and the patient underwent the procedure smoothly with no significant adverse events postoperatively.Transcatheter mitral valve-in-valve replacement may be a better alternative for patients at high risk of mitral bioprosthesis degeneration.

This study was aimed at analyzing the changes in the cell proteome of HTR-8/Svneo human villous trophoblasts during infection with Listeria monocytogenes,to explore the mechanisms involved in L.monocytogenes infection of the placenta at the molecular level in host cells.Tandem Mass Tag(TMT)proteomics was used to compare the quantitative proteome be-tween the HTR-8/Svneo infection group and control group.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used to analyze enrichment in the molecular functions,biological processes,and metabolic pathways of differentially expressed proteins.A total of 76 285 peptides and 6 979 quantifiable proteins were identified.A total of 356 proteins showed significant differential expression:153 up-regulated and 203 down-regulated.The protein with the high-est fold change was microtubule motor protein(B4DYE2),and the protein with the lowest fold change was translation initia-tion factor 1(Q6IAV3).GO functional enrichment and KEGG metabolic pathway enrichment analyses indicated that the up-regulated proteins were involved primarily in biological processes and metabolic pathways such as the movement of microtubules and microfilament as well as autophagy,whereas the down-regulated proteins were involved mainly in primary metabolic pathways,such as carbon metabolism,nitrogen metabolism,amino acid biosynthesis,and nucleic acid metabolism,as well as ubiquitin mediated protein hydrolysis.In the process of infection of HTR-8/Svneo by L.monocytogenes,the basal metabolism of host cells may be significantly diminished,and the autophagy level may be high.The significant up-regulation of cell migration-inducing and hyaluronan-binding protein CEMIP(Q8WUJ3)suggested an important role of this protein in regulating the migration and invasion of trophoblast cells,thus causing adverse pregnancy outcomes.Our findings may provide new ideas for the study of the molecular mechanism of L.monocytogenes infection of the placenta.

Objectives:To compare the diagnostic efficacy of non-ST-segment elevation myocardial infarction (NSTEMI) and the predictive value for major adverse cardiovascular events (MACE) of the 0/3-hour algorithm for high-sensitivity cardiac troponin (hs-cTn) recommended by the 2015 European Society of Cardiology (ESC) guidelines for the management of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and the 2021 "Chinese Expert Consensus on Laboratory Testing and Clinical Application of Cardiac Troponin" in suspected acute coronary syndrome (ACS) patients in the Chinese population. Methods:This is a multicenter prospective observational study,including 1527 patients with suspected ACS from three clinical centers from January 2017 to September 2020.Plasma hs-cTnI levels were measured using the ARCHITECT assay at the time of presentation and 3 hours later in patients with suspected ACS (test determination).Clinical judgment (independent clinical judgment by cardiac experts,independent of the test results) was used as the gold standard to compare the sensitivity,specificity,and consistency of the two diagnostic algorithms,and to analyze their predictive value for MACE at 30 days and 180 days.MACE in this study was defined as a composite event of cardiovascular death,myocardial infarction,and unplanned coronary revascularization. Results:According to clinical judgment,there were 400 patients with NSTEMI and 1127 patients without NSTEMI.The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus showed higher sensitivity in diagnosing NSTEMI than the 2015 ESC guidelines (91.50％[95％ CI:88.32％-94.04％]vs.87.75％[95％ CI:84.13％-90.80％]),but slightly lower specificity (93.88％[95％ CI:92.32％-95.21％]vs.95.56％[95％ CI:94.19％-96.69％]),with both differences being statistically significant (both P<0.001).In the follow-up at 30 days and 180 days,the incidence of MACE in patients diagnosed with NSTEMI by both algorithms was higher than in those without NSTEMI (P<0.001).The incidence of MACE at 30 days and 180 days for the group excluded from the diagnosis of NSTEMI by 2015 ESC guidelines was 0.19％ and 1.120％,respectively,and for the NSTEMI group was 2.89％ and 3.68％,respectively;for the group excluded from NSTEMI by the 2021 Chinese Expert Consensus,the incidence was 0.096％ and 0.770％,respectively,and for the NSTEMI group was 2.91％ and 4.36％,respectively.Cox analysis showed that the HR ratio for MACE at 180 days in the NSTEMI group diagnosed by both algorithms was 3.418 and 5.892,respectively,significantly higher than the group excluded from NSTEMI. Conclusions:The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus has superior diagnostic sensitivity compared to the 2015 ESC NSTE-ACS guidelines,at the cost of slightly lower specificity.Both algorithms can effectively predict MACE within 180 days,but based on the data from this study,the algorithm recommended by the 2021 Chinese Expert Consensus is more sensitive in predicting the risk of MACE,and patients excluded from the diagnosis of NSTEMI by this method have a lower incidence of MACE,suggesting that its application in clinical practice may be more helpful in terms of long-term safe management of patients.

Objective To explore the efficacy and safety of ultrasound-guided radiofrequency ablation combined with foam sclerotherapy in the treatment of primary small saphenous vein varicosities.Methods A total of 46 patients with primary small saphenous vein varicosities in our department from November 2021 to November 2022 were retrospectively analyzed.Depending on the patient's choice of surgical method,they underwent radiofrequency ablation combined with sclerotherapy(observation group,n=23)or high ligation and stripping of the saphenous vein(control group,n=23).The surgical time,intraoperative blood loss,length of hospital stay,postoperative Venous Clinical Severity Score(VCSS),incidence of postoperative complications,treatment satisfaction,and recurrence were compared between the two groups.Results Compared with the control group,the observation group had shorter surgical time[(56.1±6.0)min vs.(81.7±10.6)min,t=-10.128,P=0.000],less intraoperative blood loss[(27.0±4.1)ml vs.(41.4±4.8)ml,t=-11.016,P=0.000],shorter hospitalization time[(2.0±0.7)dvs.(5.6±0.9)d,t=-14.319,P=0.000],lower VCSS scores at 3,6,and 12 months after surgery[(7.4±2.0)points vs.(8.9±2.5)points,t=-2.165,P=0.036;(5.3±1.8)points vs.(6.5±2.2)points,t=-2.149,P=0.037;(2.6±1.3)points vs.(4.0±1.8)points,t=-2.912,P=0.006],higher satisfaction[satisfied,somewhat satisfied,dissatisfied in 18,4,and 1 cases in the observation group and 8,10,and 5 cases in the control group,respectively,Z=-2.967,P=0.003].There were no statistically significant differences in the complication incidence and recurrence rate between the two groups(P＞0.05).Conclusion Ultrasound-guided radiofrequency ablation combined with foam sclerotherapy in the treatment of primary small saphenous vein varicosities is safe and effective.

Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.

Objective This research aimed to investigate the expression and mechanism of miR-155 and suppressor of cytokine signaling 1(SOCS1)in rheumatoid arthritis(RA).Methods RT-PCR and flow cytometry were applied to detect the expression differences of miR-155,Th17,and Treg cells in peripheral blood of RA patients(RA group)and control group(HC group).Bioinformatics analysis and dual-luciferase reporter assay were conducted to investigate the regulatory relationship between miR-155 and SOCS1.CD4+T cells were isolated from peripheral blood of RA patients and transfected with miR-155 inhibitor,si-SOCS1,and their respective negative control sequences,and divided into four groups:miR-NC group,miR-155 inhibitor group,miR-155 inhibitor+si-NC group,and miR-155 inhibitor+si-SOCS1 group.The cells were treated with Th17-inducing differentiation medium,and flow cytometry was used to determine the ratio of Th17 cells in each group of CD4+T cells.Western blot was used to determine the ratio of p-STAT3/STAT3 in the cells.Results Compared to the HC group,RA patients showed increased expression of miR-155 and Th17 ratio(P<0.01),and decreased Treg cell ratio(P<0.01).MiR-155 could target and inhibit the expression of SOCS1.Compared to the miR-NC group,the miR-155 inhibitor group,miR-155 inhibitor+si-NC group,and miR-155 inhibitor+si-SOCS1 group showed decreased Th17 ratio and p-STAT3/STAT3 ratio(P<0.01).Compared to the miR-155 inhibitor group,the miR-155 inhibitor+si-SOCS1 group exhibited increased Th17 ratio and p-STAT3/STAT3 ratio in CD4+T cells(P<0.05).Conclusion Elevated expression of miR-155 in RA patients may mediate the differentiation of CD4+T cells into Th17 cells through the SOCS1/STAT3 pathway,contributing to the imbalance of Th17/Treg cells in peripheral blood of RA patients.

Objective To investigate the impact of Sca-1 bone marrow derived stem cells on apoptosis in murine cardiac fibroblasts and the molecular mechanisms of young(Y)Sca-1 bone marrow stem cell(BMSC)on old(O)cardiac fibroblast cell(CFC)apoptosis.Methods The apoptosis and survival of Y and O CFC were assessed under hypoxic conditions.Co-cultures of Y and O Sca-1 bone marrow-derived mesenchymal stem cells(BMSC)with O CFC were established to investigate the impact of Sca-1 BMSC on the apoptotic response and viability of O CFC,employing TUNEL staining,qRT-PCR,Western Blot,and CCK8 assays.Furthermore,differential secretion profiles of growth factors by Y and O Sca-1 BMSC were compared using qRT-PCR and ELISA analysis.Results Compared to Y CFC,O CFC exhibited an increased rate of apoptosis and a decreased rate of cell survival.However,when compared to O cells,Y Sca-1 BMC significantly reduced apoptosis in O CFC and enhanced cell survival.Moreover,Y Sca-1 BMSC demonstrated a higher secretion of GDF5(Growth Differentiation Factor 5)than O cells(P<0.05).Importantly,the protective effects of Y Sca-1 BMSC on apoptosis and survival in O CFC were abolished upon neutral-ization of GDF5 expression.Conclusion Y Sca-1 BMSC decreases O CFC apoptosis through GDF5.