OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Objective:To clarify the natural course of renal angiomyolipoma and the risk factors for its progression.Methods:This was a retrospective case-control study that included 401 patients diagnosed several times by ultrasound examination in the hospital physical examination system from January 2012 to June 2024. All patients were untreated. There were 128 male cases (31.90%) and 273 female cases (68.10%). The average age at initial diagnosis was (44.04 ± 10.24) years (range 22-78 years). The median longest diameter of the tumor at initial diagnosis was 9.0 (7.0, 11.5) mm. There were 359 cases (89.50%) with single tumors and 42 cases (10.50%) with multiple tumors. The patients were divided into the progression group(≥1 mm/year) and the non-progression group (<1 mm/year)based on the average growth rate of tumor. The differences in gender, age at initial diagnosis, initial tumor size, number of lesions and lesion site between the two groups were compared. Univariate logistic regression analysis was used to explore the relationship between the above factors and the progression of renal angiomyolipoma. Multivariate logistic regression analysis was conducted to identify the risk factors for progression.Results:A total of 401 cases were followed up for an average of (88.15 ± 21.09) months (range 48-140 months). The median maximum diameter of the tumors at the initial diagnosis was 9.0 (7.0, 11.5) mm, and at the end of the follow-up, it was 11 (8, 14) mm. The average growth rate was 0.38 mm/year, and the median growth rate was 0.25 (0, 0.60) mm/year. Among them, 341 cases (85.04%) were in the non-progression group with an average growth rate of 0.14 mm/year, and 60 cases (14.96%) were in the progression group with an average growth rate of 1.74 mm/year. The age of the progression group was lower than that of the non-progression group [(41.43 ± 9.64) years vs. (44.50±10.29) years], the initial maximum diameter of the tumors in the progression group was larger than that in the non-progression group [11.0 (8.0, 16.0) mm vs. 9.0 (7.0, 11.0) mm], and the proportion of multiple tumors in the progression group was higher than that in the non-progression group [14 cases (23.30%) vs. 28 cases (8.20%)], and the differences were all statistically significant ( P<0.05). Age at initial diagnosis( OR=0.96, 95% CI 0.93-0.99), initial tumor size ( OR=1.08, 95% CI 1.04-1.12) and number of lesions ( OR=2.96, 95% CI 1.38-6.34) were the risk factors for the growth of renal angiomyolipoma ( P<0.05), according to the results of multivariate logistic regression analysis. Conclusions:The natural history of most renal angiomyolipoma shows slow growth or relative quiescence, with a small number showing a significant increasing trend. Age at initial diagnosis, initial tumor size and number of lesions were independent risk factors for the growth of renal angiomyolipoma.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

Objective:This study aims to investigate the expression of uridine diphosphate-glucose[]pyrophos-phorylase 2(UGP2)in breast cancer(BC)tissues and its oncogenic mechanism,assessing its potential value as a diag-nostic and prognostic biomarker for breast cancer.Methods:(1)Online database analysis was conducted to assess UGP2 mRNA and protein expression levels in breast cancer and explore their correlation with clinical characteristics.Im-munohistochemistry(IHC)was used to verify UGP2 expression in human breast cancer tumor tissues and evaluate its relationship with clinicopathological features.(2)Kaplan-Meier survival analysis and COX regression models were used to analyze the impact of UGP2 expression on breast cancer patient prognosis.(3)Bioinformatics methods were em-ployed to investigate the correlation between UGP2 and tumor immune cell infiltration,and to predict the biological func-tions and associated signaling pathways of UGP2 in breast cancer.Results:(1)The mRNA and protein expression levels of UGP2 were upregulated in breast cancer tissues(both P<0.05),and were negatively correlated with ER-positive and PR-positive status(OR<1,P<0.05),while positively correlated with Ki-67 levels and the triple-negative breast cancer(TNBC)subtype(OR>1,P<0.05).(2)Elevated expression levels of UGP2 were associated with poorer survival rates in breast cancer patients(both P<0.05)and were identified as an independent adverse prognostic factor for breast cancer(HR=1.40,P<0.05).(3)Functional analysis results suggested that UGP2 may promote tumor progression by regulating metabolism,hormone signaling,and the immune microenvironment.Additionally,UGP2 expression was negatively cor-related with NK cell activation status and positively correlated with the inhibitory state.Conclusion:UGP2 expression is elevated in breast cancer tissues and is closely associated with poor patient prognosis.It may promote cancer pro-gression through mechanisms such as metabolic reprogramming and immune suppression.UGP2 shows promise as a potential biomarker and therapeutic target in breast cancer,providing a basis for personalized treatment.

Objective:To construct a predictive model for benign and malignant colorectal lesions based on modal ultrasound parameters and clinical indicators,and evaluate the effectiveness of the predictive model.Methods:Clinical data of 198 patients with colorectal lesions treated in Hebei Petro China Central Hospital from March 2020 to March 2024 were recorded.According to pathological diagnosis,they were grouped into a benign lesion group of 102 cases and a malignant lesion group of 96 cases.All patients underwent multimodal ultrasound examination.Multivariate Logistic re-gression analysis was applied to screen the influencing factors of colorectal cancer progression.R software package was applied to build a nomogram prediction model.Hosmer-Lemeshow test,calibration curve,ROC curve,and clinical deci-sion curve were used for validation.Results:There were statistically obvious differences in internal echo,morphology,blood flow signal,rise time(RT),contrast agent of"fast in and fast out",mean Young's modulus(Emean),age,positive fecal occult blood,and polyps between the benign and malignant lesion groups(P＜0.05).Uneven internal echoes,irregu-lar shapes,abundant blood flow signals,contrast agent of"fast in and fast out",age ≥ 60 years,positive fecal occult blood,and polyps ≥ 2 were independent risk factors for colorectal cancer(P＜0.05),while RT is a protective factor for colorectal cancer(P＜0.05).The internal validation results of the nomogram prediction model showed that the Hosmer-Lemeshow test showed x2=3.661 and P=0.886.The calibration curve showed that the actual probability was basically consistent with the predicted probability,and the AUC of the ROC curve was 0.802(95％CI:0.732-0.871),indicating that the calibration and discrimination of the column chart prediction model were good.Within the high-risk threshold range of 0.28-0.98,the decision curve was above the All line and None line,indicating a high net benefit and clinical practicality.Conclusion:Internal echo,morphology,blood flow signal,contrast agent of"fast in and fast out",age,positive fecal occult blood,polyps,and RT are influencing factors for the occurrence of colorectal cancer.The column chart prediction model constructed based on this has good predictive performance and provides reference for early inter-vention by clinical physicians.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.