One and five-year efficacy of tension-free vaginal tape (TVT) abbrevo and TVT-obturator in the treatment of stress urinary incontinence: a retrospective study.

BACKGROUND: Surgical interventions are more effective than nonsurgical approaches in providing a cure for stress urinary incontinence (SUI). In this study, we aimed to assess the benefits of tension-free vaginal tape (TVT) abbrevo by comparing its efficacy and complications to those of TVT obturator. METHODS AND RESULTS: 49 and 47 patients at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University between January 2013 and December 2016 were included in the TVT-O and TVT-A groups, respectively. We evaluate the success rate and perioperative complications associated with TVT-O and TVT-A. A questionnaire that utilized the Patient Global Impression of Improvement (PGI-I) Scale was employed to assess the impact of surgery. Patients were followed up at 1 year, and 5 years after surgery. There were no statistically significant differences found in the efficacy of the TVT-A group and TVT-O group during both the one-year (p = 0.4) and five-year (p = 0.32) follow-up periods. In the period of one-year follow-up, 95.9% (n = 47) of patients in the TVT-O group and 95.8% (n = 45) of patients in the TVT-A group demonstrated improvement. During the period of five-year follow-up, 87.8% (n = 43) of patients in the TVT-O group and 93.6% (n = 44) of patients in the TVT-A group demonstrated improvement. CONCLUSIONS: Based on our findings, TVT-A and TVT-O procedures exhibited similarly high success rates and low frequencies of complications.

Development and validation of a Radiopathomics model based on CT scans and whole slide images for discriminating between Stage I-II and Stage III gastric cancer.

OBJECTIVE: This study aimed to develop and validate an artificial intelligence radiopathological model using preoperative CT scans and postoperative hematoxylin and eosin (HE) stained slides to predict the pathological staging of gastric cancer (stage I-II and stage III). METHODS: This study included a total of 202 gastric cancer patients with confirmed pathological staging (training cohort: n = 141; validation cohort: n = 61). Pathological histological features were extracted from HE slides, and pathological models were constructed using logistic regression (LR), support vector machine (SVM), and NaiveBayes. The optimal pathological model was selected through receiver operating characteristic (ROC) curve analysis. Machine learnin algorithms were employed to construct radiomic models and radiopathological models using the optimal pathological model. Model performance was evaluated using ROC curve analysis, and clinical utility was estimated using decision curve analysis (DCA). RESULTS: A total of 311 pathological histological features were extracted from the HE images, including 101 Term Frequency-Inverse Document Frequency (TF-IDF) features and 210 deep learning features. A pathological model was constructed using 19 selected pathological features through dimension reduction, with the SVM model demonstrating superior predictive performance (AUC, training cohort: 0.949; validation cohort: 0.777). Radiomic features were constructed using 6 selected features from 1834 radiomic features extracted from CT scans via SVM machine algorithm. Simultaneously, a radiopathomics model was built using 17 non-zero coefficient features obtained through dimension reduction from a total of 2145 features (combining both radiomics and pathomics features). The best discriminative ability was observed in the SVM_radiopathomics model (AUC, training cohort: 0.953; validation cohort: 0.851), and clinical decision curve analysis (DCA) demonstrated excellent clinical utility. CONCLUSION: The radiopathomics model, combining pathological and radiomic features, exhibited superior performance in distinguishing between stage I-II and stage III gastric cancer. This study is based on the prediction of pathological staging using pathological tissue slides from surgical specimens after gastric cancer curative surgery and preoperative CT images, highlighting the feasibility of conducting research on pathological staging using pathological slides and CT images.

PDGFBB facilitates tumorigenesis and malignancy of lung adenocarcinoma associated with PI3K-AKT/MAPK signaling.

Lung adenocarcinoma (LUAD) remains one of the most aggressive tumors and the efficacy of conventional treatment has been bleak. Nowadays, gene-targeted therapy has become a new favorite in tumor therapy. Herein, we investigated the effect of platelet derived growth factor BB (PDGFBB) on LUAD. Firstly, PDGFBB was upregulated in LUAD patients and closely linked with poor survival. Furthermore, the expression of PDGFBB and PDGFRα/ß in LUAD cells was higher than that in normal lung cells. By loss-of-function with herpes simplex virus (HSV)-PDGFi-shRNA, we found that PDGFBB knockdown caused a significant decrease in proliferation and migration, but evoked apoptosis of LUAD cells in vitro. Conversely, exogenous PDGFBB held adverse effect. Additionally, A549 cells with PDGFBB knockdown had a low probability of tumorigenesis in vivo. Moreover, PDGFBB knockdown restrained the growth of xenografts derived from normal A549 cells. Mechanistically, PDGFBB knockdown suppressed PI3K/AKT and Ras/MAPK signaling, while PDGFBB was the opposite. Therefore, we concluded that PDGFBB might facilitate the tumorigenesis and malignancy of LUAD through its functional downstream nodes-PI3K/AKT and Ras/MAPK signaling, which supported that PDGFBB could serve as a rational therapeutic target for LUAD.

Research progress of neuronal injury mediated by microglial activation and depression / 中国药理学通报

Depression is a common neurological disorder with high incidence, high recurrence and high disability, but its pathogenesis is unclear. In recent years, the protective and attacking effects of glial cells on neurons have become the frontier of neurological disease research. Neuronal injury caused by abnormal activation of microglia (MG) plays an important role in the pathogenesis of depression. In this paper, through literature retrieval by GeenMedical and CNKI, the relevant pathways and key targets of MG activation in depression are summarized so as to provide a theoretical basis for further clinical research.

A comprehensive radiopathological nomogram for the prediction of pathological staging in gastric cancer using CT-derived and WSI-based features.

OBJECTIVE: This study aims to develop and validate an innovative radiopathomics model that combines radiomics and pathomics features to effectively differentiate between stages I-II and stage III gastric cancer (pathological staging). METHODS: Our study included 200 patients with well-defined stages of gastric cancer divided into a training cohort (n = 140) and a test cohort (n = 60). Radiomics features were extracted from contrast-enhanced CT images using PyRadiomics, while pathomics features were obtained from whole slide images of pathological specimens through a fine-tuned deep learning model (ResNet-18). After rigorous feature dimensionality reduction and selection, we constructed radiomics models (SVM_rad, LR_rad, and MLP_rad) and pathomics models (SVM_path, LR_path, and MLP_path) utilizing support vector machine (SVM), logistic regression (LR), and multilayer perceptron (MLP) algorithms. The optimal radiomics and pathomics models were chosen based on comprehensive evaluation criteria such as ROC curves, Hosmer‒Lemeshow tests, and calibration curve tests. Feature patterns extracted from the best-performing radiomics model (MLP_rad) and pathomics model (SVM_rad) were integrated to create a powerful radiopathomics nomogram. RESULTS: From a pool of 1834 radiomics features extracted from CT images, 14 were selected to construct radiomics models. Among these, the MLP_rad model exhibited the most robust predictive performance (AUC, training cohort: 0.843; test cohort: 0.797). Likewise, 10 pathomics features were chosen from 512 extracted from whole slide images to build pathomics models, with the SVM_path model demonstrating the highest predictive efficiency (AUC, training cohort: 0.937; test cohort: 0.792). The combined radiopathomics nomogram model exhibited optimal discriminative ability (AUC, training cohort: 0.951; test cohort: 0.837), as confirmed by decision curve analysis (DCA), which indicated superior clinical effectiveness. CONCLUSION: This study presents a cutting-edge radiopathomics nomogram model designed to predict pathological staging in gastric cancer, distinguishing between stages I-II and stage III. Our research leverages preoperative CT images and histopathological slides to forecast gastric cancer staging accurately, potentially facilitating the estimation of staging before radical gastric cancer surgery in the future.

Clinicopathological features and prognostic significance of pulmonary adenocarcinoma with signet ring cell components: meta-analysis and SEER analysis.

Pulmonary adenocarcinoma is a common type of lung cancer that has been on the rise in recent years. Signet ring cell components (SRCC) can be present in various patterns of pulmonary adenocarcinoma, including papillary, acinar, and solid patterns. "Signet ring cell carcinoma" is a distinct subtype in the 2014 WHO classification of lung neoplasms, subsequent WHO classifications in 2015 and 2021 have deemed signet ring cells as accompanying morphological features with no clinical significance. The prognostic and clinical implications of SRCC in pulmonary adenocarcinoma remain controversial. Therefore, we conducted a meta-analysis to investigate the clinicopathological features and prognostic factors of SRCC in pulmonary adenocarcinoma. We conducted a comprehensive search in PubMed, EMBASE, and Web of Science to identify studies that examined the clinicopathological features and prognostic implications of pulmonary adenocarcinoma with SRCC. We used both fixed- and random-effects models to analyze the data and calculate the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). Additionally, we explored the prognostic significance of SRCC in pulmonary adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database. Our meta-analysis included 29 studies with pulmonary adenocarcinoma and SRCC components. The results showed that pulmonary adenocarcinoma with SRCC was associated with larger tumor size (OR = 1.99; 95% CI, 1.62-2.44, p < 0.001), advanced overall stage (OR = 5.18, 95% CI, 3.28-8.17, p < 0.00001) and lymph node stage (OR = 5.79, 95% CI, 1.96-17.09, p = 0.001), and worse overall survival (OS) compared to those without SRCC (HR = 1.80, 95% CI, 1.50-2.16, p < 0.00001). Analysis using the SEER dataset confirmed these findings. Our meta-analysis provides evidence that pulmonary adenocarcinoma with SRCC is associated with distinct clinicopathological features and a poorer prognosis. These findings have important implications for the management and treatment of patients. However, further studies are needed to validate these findings and explore the significance of SRCC in various subtypes of pulmonary adenocarcinoma.

Effects of different fertilization treatments on soil microbial functional diversity of dry tableland wheat field in south Shanxi Province.

Understanding the effects of different fertilization treatments on microbial functional diversity in loess tableland wheat soil in south Shanxi Province can provide the theoretical basis from the perspective of microbial functional diversity for chemical fertilizer reduction, wheat yield increase, and soil fertility improvement in dryland soil. We conducted a long-term field experiment with seven fertilization treatments in winter wheat cultivation area of loess tableland in south Shanxi Province, including straw charcoal fertilizer (SF), bacterial fertilizer (BF), organic fertilizer (OF), humic acid fertilizer (HF), monitoring fertilizer (MF), farmer fertilizer (FF) and no fertilizer (CK). We employed Biolog-ECO microplate technique to investigate the differences of carbon source utilization capacity and functional diversity of soil microorganisms. The results showed that all the fertilization treatments could improve the metabolic activity and functional diversity of soil microbial community. Carbon source utilization was the most efficient in SF, with the overall soil microbial utilization ability of the 31 carbon sources and the utilization ability of different guilds of carbon sources being improved. Functional diversity, richness, and dominance based on microbial carbon sources utilization were significantly higher in SF treatment than that under other five treatments, and the evenness was higher than BF. Results of principal component analysis (PCA) and biclustering heatmap analysis showed that different fertilization treatments had significant effects on the metabolic function of microbial community. SF treatment could promote the functional diversity of soil microbial community, especially for the utilization of carbohydrates, carboxylic acids and amino acids. In conclusion, straw charcoal fertilizer had positive effects on soil microbial activity in wheat soil of loess tableland in south Shanxi Province.

Nur77 Serves as a Potential Prognostic Biomarker That Correlates with Immune Infiltration and May Act as a Good Target for Prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD) is the most frequent malignancy, and is the second leading cause of death due to cancer in men. Thus, new prognostic biomarkers and drug targets for PRAD are urgently needed. As we know, nuclear receptor Nur77 is important in cancer development and changes in the tumor microenvironment; whereas, the function of Nur77 in PRAD remains to be elucidated. The TCGA database was used to explore the Nur77 expression and its role in the prognosis of PRAD. It was shown that Nur77 was down regulated in PRAD, and low Nur77 expression was correlated with advanced clinical pathologic characteristics (high grade, histological type, age) and poor prognosis. Furthermore, key genes screening was examined by univariate Cox analysis and Kaplan-Meier survival. Additionally, Nur77 was closely related to immune infiltration and some anti-tumor immune functions. The differentially expressed genes (DEGs) were presented by protein-protein interaction (PPI) network analysis. Therefore, the expression level of Nur77 might help predict the survival of PRAD cases, which presents a new insight and a new target for the treatment of PRAD. In vitro experiments verified that natural product malayoside targeting Nur77 exhibited significant therapeutic effects on PRAD and largely induced cell apoptosis by up-regulating the expression of Nur77 and its mitochondrial localization. Taken together, Nur77 is a prognostic biomarker for patients with PRAD, which may refresh the profound understanding of PRAD individualized treatment.

Comparison of immunization strategies for human rabies pre-exposure prophylaxis in laboratory animals / 中华微生物学和免疫学杂志

Objective:To compare the differences in the safety, efficacy and protective effects of rabies vaccine using the current pre-exposure prophylaxis schedule in China (0-7-21 or 28) and the newly recommended immunization program of WHO (0-7), aiming to provide data support for modifying the related content of Technical Guideline for Human Rabies Prevention and Control. Methods:The mice were randomly divided into five groups, namely 0-7-21 group (3-injection regimen), 0-7 group (2-injection regimen), 0-14 group, 0-21 group and control group, according to the current 3-injection regimen (0-7-21) in China and the 2-injection regimen (0-7) recommended by WHO. The survival status of the mice was observed. The mice were weighed every five days to compare the safety of different immunization procedures. Rabies virus neutralizing antibodies (RVNA) were detected 7, 14, 21, 28 and 35 d after the initial immunization. On day 35, the mice in each group were challenged with lethal dose of CVS-11 rabies virus to evaluate the protective effects of different pre-exposure immunization procedures.Results:There was no significant difference in weight gain of mice after vaccination. The positive rate of RVNA was 100% in all immunized groups from day 14, which could provide complete protection to mice. There was a significant difference in RVNA levels between 0-7-21 and 0-7 groups at 35 d( P<0.05), but there was no statistical difference at other time points ( P>0.05). RVNA level had a significant difference between 0-7 and 0-21 groups at 21 d and 35 d ( P<0.05). There was no statistical difference in RVNA level between other groups at each time point ( P>0.05). In the protective test, the survival rates of mice in all immune groups were 100%. Conclusions:The current 3-injection pre-exposure immunization procedure for rabies vaccine (0-7-21) and the newly recommended 2-injection immunization procedure (0-7) had similar efficacy and protective effects in animal tests. In view of the cost saving and better compliance of the 2-injection immunization procedure, it was recommended that relevant departments should conduct clinical trials as soon as possible to promote the implementation of this program.

Application of preoperative and intraoperative electroneurophysiological examination for persons with hemifacial spasm / 中华物理医学与康复杂志

Objective:To analyze the diagnostic value of preoperative electromyography and spasticity assessment for patients with hemifacial spasm, and to define a relationship between intraoperative electrophysiological examination and prognosis in order to provide help for clinical diagnosis and treatment.Methods:Thirty-one patients with hemifacial spasm were selected for the clinical spasticity scoring and divided into a general spasm group ( n=27) and a severe spasm group ( n=4). All received preoperative neurophysiological examination to record their twitch discharge, facial nerve conduction velocity (MCV), lateral spread (LSR) of the spasm, brainstem auditory evoked potential (BAEP), and blink reflex. Electrophysiological monitoring then recorded intraoperative LSR. According to whether the LSR disappeared or not, the patients were divided into the LSR disappearance group (of 15) and the LSR residual group (of 16), and facial muscle activity was recorded again one, three and six months after the operation. Results:Preoperative EMG examination of both groups showed positive LSR and that facial nerve MCV was within the normal range. There were, though, significant differences between the two groups in the twitching discharge by needle electromyography, blink reflex and preoperative BAEP. One week after the operation, one member of the residual group and 3 from the disappearance patients of the former and latter group had recovered in terms of LSR, with 3 and 7 cases significantly relieved, respectively. Two months later, the corresponding figures were 5 and 7, 3 and 6, respectively. Half of a year after the surgery, 5 from the residual group and 12 from the disappearance group had fully recovered in terms of LSR, while 9 and 2 cases were significantly relieved. Altogether, there were significant differences within the two groups in terms of recovery among all the time points, with significantly better recovery in the LSR disappearance group than the LSR residual group at 1 week after operation, while there were no significant differences between the two groups in recovery 3 and 6 months after their operation.Conclusions:Preoperative electromyography can provide objective assessments of the scope, severity, and facial nerve excitability of patients with hemifacial spasm. Real-time intraoperative electrophysiology monitoring can help surgeons to objectively assess the effect of decompression and to find and avoid nerve traction injury in surrounding areas quickly.

Investigation of anxiety and depression of postgraduates in military medical university under public health emergencies / 中华医学教育探索杂志

Objective:To investigate the characteristics of anxiety and depression of postgraduates in military medical university under public health emergencies.Methods:By means of self-rating anxiety scale (SAS) and self-rating depression scale (SDS), 944 postgraduate students of a military medical university were investigated to analyze their characteristics of anxiety and depression. SPSS 25.0 was used to statistically analyze the collected data.Results:①The positive rates of anxiety and depression were respectively 8.03% and 8.25%. ②The positive rate of anxiety of male postgraduates was significantly higher than that of female postgraduates ( P=0.035). ③The positive rate of anxiety of serviceman students was significantly higher than that of civilian students ( P=0.022). ④There was no statistical difference in the positive rates of anxiety and depression among postgraduates in different areas ( P > 0.05). ⑤The levels of anxiety and depression of left-behind children were significantly higher than those of unleft-behind children ( P=0.000, P=0.018). ⑥The levels of anxiety and depression of postgraduate students were lower than those of undergraduate students ( P=0.000, P=0.002). Conclusion:Under the outbreak of public health emergencies, anxiety and depression occur in the postgraduates. To strengthen the mental health maintenance of postgraduates in military medical university during the outbreak, it is necessary to pay more attention on the mental health of military students, males and who were left-behind children before.

Exploration and practice of hierarchical training model for improving professional ability of primary pediatricians / 中华医学教育探索杂志

At present, the routine specialized training for primary pediatricians (focusing on theoretical learning of public subjects) cannot meet the needs of primary pediatricians. In order to promote the development of children's medical care at the grassroots level and improve the quality, medical and clinical research abilities of regional pediatric medical personnel, the Children's Hospital of Chongqing Medical University has designed and built a "hierarchical training model for improving the professional ability of pediatricians" from the aspects of training objectives, training contents, training methods, construction and evaluation of training programs, and quality control. In addition, the 8-month "Pediatric Professional Basic Training" and the 9-month "Pediatric Professional Ability Improvement Training" were respectively carried out in Xianyang Children's Hospital. In the "Professional Basic Training", 88 trainees were comprehensively evaluated after training, 53 of whom were qualified or above. In the "Ability Improvement Training", 26 of the 29 students actually participated in the evaluation and reached the qualified level or above. Learners provided feedbacks that they have effectively improved their own knowledge structure, expanded their clinical diagnosis and treatment thinking and clinical research ideas, and provided some guidance for clinical work.

Application of teacher standardized patients combined case-based leaching in the acceptation ability training of general practitioners in medically unexplained physical symptoms / 中华医学教育探索杂志

Due to the reduction of patient cooperation and the limitation of clinical diseases, general practitioners lack effective acceptation training in the training process. To improve this situation, this study applies teacher standardized patients (TSP) combined case-based learning (CBL) to the acceptation ability training of general practitioners in medically unexplained physical symptoms (MUPS). And the acceptation ability and communication ability of 15 general practitioners were evaluated before, during and after the training. It shows that the application of "TSP + CBL" in the acceptation ability training of general practitioners in MUPS can effectively improve the acceptation ability and communication ability of general practitioners.

Evaluation on the application effect of "flipped classroom" in general surgery practice teaching / 中华医学教育探索杂志

Objective:To explore the application and practice of "flipped classroom" in the teaching of general surgery interns.Methods:A total of 20 internship groups (3 to 5 people in each group) were randomly selected from the general surgery practice group in the Department of General Surgery of the Second Clinical Medical College of North Sichuan Medical College. They were randomly divided into the flipped group (45 people) and the traditional group (40 people), with 10 subgroups in each group. The flipped group adopted the flipped classroom teaching mode (students' self-study by handing out materials before class, students and teachers' discussion in class, and students and teachers' evaluation after class), while the control group adopted the current conventional teaching mode (students' preview before class, teachers' explanation in class, and teachers' question answering after class). At the end of the teaching, a questionnaire was used to evaluate the participation and completion of each student. The teaching effect was evaluated by medical history collection and case analysis. The participation, completion, and teaching effect between the two groups were compared and analyzed. SPSS 23.0 software was used for t-test and Chi-square test. Results:The participation of the flipped group was better than that of the traditional group [(17.45±1.83) vs. (15.57±1.52)], and the difference was statistically significant ( P < 0.05). There was no statistically significant difference between the flipped group and the traditional group. There was no significant difference in medical history collection scores between the two groups. The case analysis of the flipped group was better than that of the traditional group [(87.30±6.06) vs. (81.50±5.88), P < 0.05]. The questionnaire shows that about 90% of the students think that flipped classroom can improve their interest in learning [96% (43/45)], improve their autonomous learning ability [89% (40/45)], and have better learning effect. At the same time, 78% (35/45) of students think that learning time is too long. Conclusion:The flipped classroom teaching model can improve the teaching participation of general surgery students, improve students' interest in learning, improve their self-learning ability, and improve students' thinking ability of medical record analysis.

Assessment of Vasodilation Function in Diabetic Patients via Skin Temperature Variation Signals / 医用生物力学

Objective A program-controlled flexible multi-point temperature measurement device was self developed for collection and analysis of skin temperature signals of diabetic patients and healthy subjects under resting and heating conditions so as to assess vasodilation function of the microcirculation, Methods With reference to the endothelial regulation spectrum of human body, wavelet analysis was performed on skin temperature signals, and the temperature fluctuation amplitudes in diabetic group and healthy control group were compared at different time periods after thermal stimulation. Results The temperature fluctuation amplitude in endothelial spectrum of diabetic group was smaller than that of healthy control group, and the decrease in skin temperature fluctuation after the power-off of thermal stimulation was remarkably smaller than that of control group, indicating that the response to thermal stimulation for diabetic patients was slower. Conclusions Vasodilation function can be quantitatively evaluated by using the fluctuation of skin temperature signals in endothelial spectrum band. Skin temperature monitoring is a potentially easy-implemented method for the health management and early diagnosis of microvascular diseases in diabetic patients.

Effects of Coating Method on Fabrication Quality of Flexible Silicone Blood Vessels / 医用生物力学

Objective To investigate the effect of different coating methods on production quality of complex and flexible silicone vascular replicas. Methods Based on models of anterior communicating artery aneurysms, several patient-specific models were made by using spray-coating method and brush-spin-coating method respectively, and two methods for making the same vascular structure were quantitatively compared in terms of thickness growth, circumferential uniformity and light transmittance. Results Brush-spin-coating method was better than spray-coating method in the thickness control and coating uniformity for fabrication of vessels with large curvature, variable diameter and straight tube, and the model had preferably light transmittance and surface smoothness. The relative deviation of thickness by brush-spin-coating method was decreased by 8. 9% , 10. 8% and 16. 9% respectively compared with spray-coating method. Conclusions At present stage, the brush-spin coating method has the advantage of thickness uniformity and light transmittance over the spray-coating method in making silicone phantoms, and it has promising application prospects in fluid mechanics field of in vitro experiment on large vessels.

Screening of key targets for diabetic cardiomyopathy based on transcriptomics and proteomics / 中国药理学通报

Aim To explore a potential new target for the prevention and treatment of diabetic cardiomyopathy ( DCM) in mice. Methods The myocardial proteomics of normal and diabetic mice was studied. The GEO database GSE161931 dataset was analyzed using R language with P < 0.05 and I log

Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder / 中华病理学杂志

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.