OBJECTIVE To establish a clinical comprehensive evaluation framework for direct oral anticoagulants （DOACs） in the prevention of cancer-associated venous thromboembolism （CAVTE）， providing a methodological reference for the rational prevention and treatment of CAVTE as well as for the formulation and adjustment of macro-management strategies for anticoagulant drugs. METHODS Through literature retrieval， evaluation indicators were collected and organized to establish a preliminary indicator pool. The selection of evaluation indicators was carried out through two rounds of Delphi surveys using average score of indicator importance≥3.5 and a coefficient of variation （CV） ＜0.25 as the screening criteria. Analytic hierarchy process （AHP） was employed to finalize the indicator weights. RESULTS The authority levels （C）r of the two rounds of expert consultations were 0.877 and 0.943， with CV of 0.24 and 0.18， respectively. The Kendall concordance coefficients were 0.331 and 0.535 （P＜0.05）. After expert validation， six primary indicators and forty-six secondary indicators were finalized for inclusion in the evaluation framework. The primary indicators and their weightings， ranked in descending order， were as follows：“ effectiveness” （38.86%）， “safety” （38.86%），“ cost-effectiveness” （10.67%），“ accessibility” （5.51%），“ suitability” （3.48%）， and “innovation” （2.64%）. The secondary indicators exhibited a weight range from 0.02% to 20.25%， with the top five secondary indicators being：“ incidence of intracranial hemorrhage” （20.25%）， “reduction in all-cause mortality” （15.29%）， “decrease in the incidence of pulmonary embolism” （8.82%）， “reduction in the incidence of deep vein thrombosis” （7.25%）， and “drug contraindications” （4.74%）. CONCLUSIONS This study has established an authoritative， scientific， and reliable comprehensive clinical evaluation framework for the use of DOACs in the prevention of CAVTE.

Objective To identify and analyze risk factors for acute renal failure (ARF) following lung transplantation and to develop a predictive model. Methods Data for this study were obtained from the United Network for Organ Sharing (UNOS) database, encompassing patients who underwent unilateral or bilateral lung transplantation between 2015 and 2022. We analyzed both preoperative and postoperative clinical characteristics of the patients. A combined approach utilizing random forest and least absolute shrinkage and selection operator (LASSO) regression was employed to identify key factors associated with the incidence of ARF post-transplantation, based on which a nomogram model was developed. The predictive performance of the constructed model was evaluated in both training and validation sets, using receiver operating characteristic (ROC) curves and area under the curve (AUC) metrics to verify and compare model effectiveness. Results A total of 15 110 lung transplantation patients were included in the study, consisting of6 041 males and 9 069 females, with a median age of 62.00 years (interquartile range: 54.00 to 67.00). The analysis revealed statistically significant differences between postoperative renal dialysis and non-dialysis patients regarding preoperative lung diagnosis, estimated glomerular filtration rate (eGFR), mechanical ventilation, preoperative ICU treatment, extracorporeal membrane oxygenation (ECMO) support, infections occurring within two weeks prior to transplantation, Karnofsky Performance Status (KPS) score, waitlist duration, double-lung transplantation, and ischemia time (P<0.05). Five key variables associated with ARF after lung transplantation were identified through random forest and LASSO regression: recipients’ eGFR, preoperative ICU treatment, ECMO support, bilateral lung transplantation, and ischemia time. A nomogram model was subsequently established. Model evaluation demonstrated that the constructed predictive model achieved high accuracy in both training and validation sets, with favorable AUC values, confirming its validity and reliability. Conclusion This study identifies common risk factors for ARF following lung transplantation and introduces an effective predictive model with potential clinical applications.

Objective To investigate the effect of WNK2 on the ERK1/2/ROS/SHP2 signaling pathway in hepatocellular carcinoma(HCC)and to explore its role in cell proliferation and migration in HCC.Methods HepG2 cells were transfected with WNK2-mimic,sh-RNA WNK2,and corresponding negative control.The effect of WNK2 on the proliferation of HCC was examined by subcutaneous tumorigenesis assay in BALB/c nude mice.The expressions of WNK2,p40,gp90,p-SHP2,p-AKT,and p-ERK1/2 in tumor tissues were detected by Western Blot.After treatment with SHP2 inhibitor PHPS1,the expressions of WNK2,P40,gp90,p-SHP2,p-AKT,and p-ERK1/2 in HepG2 cells were detected by Western Blot.The migration ability and invasion ability of HepG2 cells were detected by cell scratch assay and Transwell.The proliferation ability of HepG2 cells was detected by monoclonal proliferation assay.Results Compared with the sh-NC group,the tumor volume of nude mice in the sh-RNA WNK2 group was significantly increased(P＜0.01);Compared with the NC-mimic group,the tumor volume of nude mice in the WNK2-mimic group was significantly reduced(P＜0.01).Western Blot result showed that compared with the sh-NC group,the expression of WNK2 in the sh-RNA WNK2 group was significantly decreased(P＜0.01),while the expressions of p40,gp90,p-SHP2,p-AKT and p-ERK1/2 were significantly increased(P＜0.01).Compared with the NC-mimic group,the expression of WNK2 was significantly increased in the WNK2-mimic group(P＜0.01),and the expressions of p40,gp90,p-SHP2,p-AKT,and p-ERK1/2 were significantly decreased(P＜0.01).In vitro experiment,compared with the sh-NC group,the expression of WNK2 was significantly decreased in the sh-RNA WNK2 group(P＜0.01),while the expressions of p40,gp90,p-SHP2,p-AKT and p-ERK1/2 were significantly increased in the sh-RNA WNK2 group(P＜0.01).Compared with the sh-NC+PHPS1 group,the expression of WNK2 was significantly decreased in the sh-RNA WNK2+PHPS1 group(P＜0.01),while the expressions of p40,gp90,p-SHP2,p-AKT,and p-ERK1/2 were reversed and had no significant differences compared with the sh-NC+PHPS1 group(P＞0.05).The cell scratch assay and Transwell result showed that the migration and invasion ability of HepG2 cells in the sh-RNA WNK2 group was significantly increased compared with the sh-NC group(P＜0.01).The migration and invasion ability of HepG2 cells in the sh-NC+PHPS1 group and sh-RNA WNK2+PHPS1 group were significantly decreased with no significant difference(P＞0.05).The result of the monoclonal proliferation experiment showed that the proliferation capacity of HepG2 cells in the sh-RNA WNK2 group was significantly increased compared with the sh-NC group(P＜0.01),while the proliferation ability of HepG2 cells in the sh-NC+PHPS1 group and sh-RNA WNK2+PHPS1 group was significantly decreased with no significant difference(P＞0.05).Conclusions WNK2 can inhibit the ERK1/2/ROS/SHP2 signaling pathway,thereby inhibiting ERK1/2/Akt signaling and delaying the proliferation and migration of HCC.

The healing process of skin wounds caused by severe mechanical trauma and chronic diseases(e.g.,diabetic foot ulcers)is often accompanied by tissue injury,microbial infection,intense inflammatory reactions,hypertrophic scars,and other complications.Microneedles have been widely used to facilitate wound healing in recent years.According to their different modes of action,microneedle formulation can be categorized into five types:solid microneedles,hollow microneedles,coated microneedles,soluble microneedles,and hydrogel microneedles.This paper reviews the preparation methods and characteristics of microneedles,and summarizes their roles in hemostasis,bacteriostasis,anti-inflammation,enhancement of collagen deposition,and angiogenesis,in the hope of providing some reference for future research and development.

Objective:To investigate the relationship between cerebrovascular variation and the occurrence and recurrence of cerebral infarction, and provide a theoretical basis for the precise prevention and treatment of cerebral infarction.Methods:Totally 13 939 patients who underwent magnetic resonance imaging(MRI) and magnetic resonance angiography(MRA) examination at the Second Affiliated Hospital of Shandong First Medical University from January 2020 to December 2021 were grouped according to clinical symptoms combined with the imaging report, including 4 412 cases in the cerebral infarction group and 9 527 cases in the control group.2 048 patients in the cerebral infarction group were eventually enrolled in the study according to the inclusion and exclusion criteria, including 1 479 cases of initial cerebral infarction and 569 cases of recurrent cerebral infarction.SPSS 25.0 statistical software was used for data analysis.The χ2 test was used to compare the incidence of cerebral infarction with different cerebrovascular variations.Univariate analysis of suspected risk factors for recurrent cerebral infarction was performed with χ2 test, nonparametric test and t test.The binary logistic regression was used to analyze independent risk factors of recurrent cerebral infarction. Results:The incidence of cerebral infarction in the dual-system cerebrovascular variant patients, the single-system cerebrovascular variant patients, and the non-cerebrovascular variant patients were 40.9%, 30.7% and 31.8% respectively.The incidence of cerebral infarction in the dual-system cerebrovascular variant patients was the highest compared with those in the single-system cerebrovascular variant patients and the non-cerebrovascular variant patients (both P<0.05). The incidence rates of embryonic posterior cerebral artery, vertebral artery dominance, and bilateral common origin anterior cerebral arteries were 14.09%, 10.76% and 5.32%, respectively.The incidence of bilateral common origin anterior cerebral arteries in the cerebral infarction group was significantly higher than that in the control group and the difference was statistically significant.Patients with cerebral infarction who were familial aggregation ( OR=2.207, 95% CI=1.591-3.062), hyperhomocysteinemia ( OR=1.262, 95% CI=1.014-1.570), hypertension ( OR=1.461, 95% CI=1.114-1.918), diabetes mellitus ( OR=1.348, 95% CI=1.072-1.694), coronary heart disease ( OR=1.491, 95% CI=1.196-1.858) were more likely to recurrent cerebral infarction ( P<0.05), and patients with cerebral infarction had a significantly increased risk of recurrent cerebral infarction with age ( OR=1.031, 95% CI=1.020-1.042, P<0.05). Conclusion:Dual-system cerebrovascular variation and bilateral common origin anterior cerebral arteries are risk factors for cerebral infarction.

Course paper grading often involves subjective factors. Teachers may introduce biases into the grading due to their preferences for certain topics, resulting in inaccurate grading results that fail to reflect the true abilities of students. Taking the grading results of the "Clinical Pharmacology" course as an example, this article investigates the analytical method for detecting topic bias in the course paper grading. A comparative analysis was performed on the differences in the scores between different topics graded by the same teacher and between the same topic graded by different teachers by calculating the vertical bias factor and the horizontal bias factor, and a scientific and feasible analytical method was established. This method can help teachers quickly discover biases in their course paper grading, thereby making the grading more objective and accurate.

Objective:To explore the application effect of BOPPPS teaching model and "Internet + WeChat" platform in the teaching of Clinical Pharmacology.Methods:Undergraduate students from two consecutive batches of clinical medicine in Wuhan University were selected as the control group and the experimental group. The control group adopted the traditional teaching method, and the experimental group adopted the BOPPPS teaching model combined with the "Internet + WeChat" platform. SPSS 12.0 was used for t test. Results:The scores of the final test in the experimental group and the control group were (86.34±7.36) and (80.77±9.21), respectively, with statistical significance ( P<0.05). For the questions of clinical case analysis, with a total score of 20 points, the scores of the experimental group students (13.31±2.25) were significantly higher than those of the control group (10.58±3.04), with significant difference ( P<0.001). Conclusion:The application of BOPPPS model and "Internet + WeChat" platform in the undergraduate teaching of Clinical Pharmacology could improve students' examination performance, and especially the ability of solving clinical problems comprehensively.

Objective:To investigate the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment. Methods:125I-RSOAds-hTERT/PSA ( 125I-virus complex) oncolytic adenovirus was constructed by PCR amplification and double restriction enzyme ligation. TUNEL staining, flow cytometry and Caspase-3 immunoblotting assay were used to detect the killing effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on prostate cancer cells in vitro and in vivo, respectively. To explore the effect of 125I-virus complex on tumor tissue cytokine secretion levels, interleukin 2 (IL-2), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the culture supernatant of human prostate cancer cell line PC3, mouse prostate adenocarcinoma cell line RM-1, and mice serum were detected by ELISA. We explored the regulation of 125I-virus complex on the expression of CD24, CD44 and prostate stem cell antigen (PSCA) in prostate tumor tissues and tumor cells through immunohistochemistry. Meanwhile, the expression levels of CD32 and vascular endothelial growth factor (VEGF), as well as CD4+ , CD8+ and macrophage infiltration in tumor tissue were detected through immunofluorescence experiments. Results:125I-virus complex oncolytic adenovirus significantly increased tumor cell apoptosis in vitro and in vivo that was significantly higher than that of 125I group and virus complex group. Meanwhile, IL-2 ( t=-183.30, -38.20, P<0.05), IL-10 ( t=113.80, 92.71, P<0.05), TNF-α ( t=-73.20, -73.91, P<0.05), IFN-γ ( t=-65.37, -139.70, P<0.05) increased in vitro and in vivo. 125I-virus complex reduced the expression of CD24, CD44 and PSCA in tumor cells and tumor tissue, reduced the weight of tumor tissue, inhibited angiogenesis of tumor tissue ( t=8.55, P<0.05), and regulated the immune response in tumor tissue. Conclusions:125I-virus complex targeting prostate cancer can significantly kill cancer cells, reduce the weight and angiogenesis of tumor, and improve tumor microenvironment.

Objective To carry out a meta-analysis,in order to evaluate the effectiveness and safety of the duodenum-preserving pancreatic head resection (DPPHR) and pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy(PPPD) for surgical treatment of chronic pancreatitis.Methods Medline,EMBASE,Cochrane library and other medical databases were searched for the clinical trials (randomized controlled trials) of comparing DPPHR Versus PD/PPPD.A total of 5 clinical trials (8 references) met the inclusion criteria.The data were analyzed using the RevMan 5.3 software.Results The two methods don't have statistical differ ence in terms of operation time (P=0.007),postoperative morbidity (P=0.35) and mortality (P=0.18),pain relief(P=0.36),new onset of diabetes(P=0.11),exocrine insufficiency(P=0.18),short-term(P=0.14) and long-term(P=0.16) quality of life score,the length of hospital stay (P=0.69),and pancreatic fistula (P=0.78).Weight gain (P＜0.000 01) and occupational rehabilitation (P=0.03)were significantly improved in the DPPHR group.However,PD/PPPD group was associated with fewer readmission due to pancreatic diseases.Conclusions DPPHR offers more advantages with regard to the quality of life.However,it needs more high-quality clinical trials to verify the results.

Objective To explore the effect and molecular mechanism of CC chemokine ligand 2 (CCL2) on epithelial-mesenchymal transition in human breast cancer cells.Methods Breast cancer Michigan cancer foundation-7 (MCF-7) cells were treated with 50 ng/ml CCL2.The abilities of invasion were detected by Transwell assay.The expression of epithelial-mesenchymal transition (EMT)-associated markers,E-cadherin and vimentin were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).The expressions of Snail,protein kinase B (AKT),phosphorylated protein kinase B (p-AKT),phosphorylated glycogen synthase kinase 3β (p-GSK3β3) and GSK3β were detected by Western blot.Snail nuclear localization was detected by immunoflurescence staining.Results We found that CCL2 treatment could induce morphological alteration of MCF-7 cells from epithelial morphology to mesenchymal morphology.CCL2 significantly increased the migration of MCF-7 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More important,treatment of CCL2 significantly increased the expression of Snail,and promoted the nuclear localization of Snail.Knockdown of Snail significantly reverse the effects of CCL2 on the EMT in MCF-7 cells.Moreover,treatment of CCL2 significantly increased the phosphorylation levels of p-AKT and p-GSK3β,and AKT inhibitor LY294002 significantly inhibited CCL2-induced Snail and p-GSK3β expression.Conclusion CCL2 might induce EMT in MCF-7 cells,by which mechanism is related to activate AKT/GSK3β Snail pathway.