Single-Cell Data Analysis Reveals Critical Hepatic Cells Subpopulations in the Progression of Non-alcoholic Fatty Liver Disease to Non-Alcoholic Steatohepatitis.

AIMS: The aim of this study was to reveal the hepatic cell landscape and function in the progression of NAFLD to NASH. BACKGROUND: Non-alcoholic steatohepatitis (NASH) is the progressive form and turning point of nonalcoholic fatty liver disease (NAFLD), which severely causes irreversible cirrhosis as well as hepatocellular carcinoma. The mechanism underlying the progression of NAFLD to NASH has not been revealed. Unraveling the mechanism of action of NAFLD-NASH is an important goal in improving the survival of patients with liver disease. OBJECTIVE: The aim of this study is to discover heterogeneous hepatic cells during the progression of NAFLD to NASH. METHODS: Single-nucleus RNA-seq (snRNA-seq) data containing NASH in NAFLD samples were obtained from the Gene Expression Omnibus (GEO) database. Cell types in liver tissues from NASH and NAFLD were identified after dimensionality reduction analysis, cluster analysis, and cell annotation. The cell pathways in which differences existed were identified by analyzing metabolic pathways in Hepatic cells. We also identified cell subpopulations in Hepatic cells. The developmental trajectories of Hepatic cells were characterized by pseudotime trajectory analysis. Single-cell regulatory network inference and clustering analysis identified key transcription factors and gene regulatory networks in Hepatic cells. Moreover, cell communication analysis determined the potential interactions between Hepatic cells and immune cells, and heapatic stellate cells. RESULTS: Seven cell types were identified in NAFLD and NASH. The proportion of Hepatic cells was lower in NASH and showed greater energy metabolism and glucose metabolism activity. Hepatic cells exhibited heterogeneity, showing two cell subpopulations, Hepatic cells 1 and Hepatic cells 2. Dysregulation of lipid metabolism in Hepatic Cell 2 resulted in lipid accumulation in the liver, which might be involved in the progression of NAFLD. Four key transcription factors, BHLHE40, NFEL2L, RUNX1, and INF4A, were primarily found in Hepatic cells 2. The transcription factors within the hepatic cells 2 subpopulation mainly regulated genes related to lipid metabolism, energy metabolism, and inflammatory response. The cell communication analysis showed that hepatocyte interactions with immune cells were associated with inflammatory responses, while interactions with hepatic astrocytes were associated with liver injury and hepatocyte fibrosis. CONCLUSION: The hepatic cells 2 might promote the progression of NAFLD to NASH by regulating metabolic activity, which might contribute to liver injury through inflammation.

Posterior mediastinal leiomyosarcoma: Case report and literature review.

BACKGROUND: Posterior mediastinal leiomyosarcoma is an extremely rare malignant mesenchymal tumor with no special clinical symptoms, which is easily confused with some common tumors in the posterior mediastinum, affecting the accuracy of the first diagnosis by clinicians and delaying the treatment of patients. CASE SUMMARY: We report a 59-year-old woman with a space-occupying lesion in the posterior mediastinum. The patient was mistakenly diagnosed with lumbar muscle or vertebral body lesions due to chest and back pain and underwent conservative treatment, but her symptoms did not improve significantly and she gradually developed pain in both lower limbs. Chest computed tomography (CT) scan indicated the left lower lung paraspinal space and underwent standard single-aperture video-assisted thoracoscopic surgery (VATS), which was pathologically confirmed as posterior mediastinal leiomyosarcoma. CONCLUSION: Complete surgical resection of posterior mediastinal leiomyosarcoma can achieve good clinical results.

A Delphi Method Comfort Status Scale for Patients With Lung Cancer After Thoracoscopic Surgery.

PURPOSE: To construct the comfort status scale for patients with lung cancer after thoracoscopic surgery. DESIGN: Delphi method inquiry to 15 clinical and nursing experts. METHODS: On the basis of the comfort status scale and the subjective experience and objective symptoms of patients with lung cancer after thoracoscopic surgery, the relevant literature was consulted, semistructured interviews and group discussions were conducted, the pool of items of the postoperative comfort status scale for patients with lung cancer was initially formed, and the postoperative comfort status scale for patients with lung cancer was finally established. FINDINGS: The positive coefficient of experts was 100%, the coefficient of authority was 0.92 and 0.93, and the Kendal's W was 0.257 and 0.298, the degree of coordination of expert opinions was statistically significant (P < .05). Finally, a total of 28 items in four dimensions were formed to assess the postoperative comfort status of patients with lung cancer after thoracoscopic surgery. CONCLUSIONS: The Delphi method-based comfort status scale for patients with lung cancer after thoracoscopic surgery is scientific and reliable, and can provide a quantitative basis for the evaluation of the comfort status of patients after lung cancer thoracoscopic surgery, to further provide individual comfort care measures.

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.

Multifunctional agents based on 3-dicycanovinylindan-1-one acceptor: Molecular design and phototheranostic application.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered considerable attention in recent years, owing to its precise spatiotemporal accuracy with minimal side effects. Recent research reveals that the combination of PDT and PTT exhibits a remarkable anti-tumor efficacy compared to PDT or PTT alone, which has put forward the new requirements of multifunctional phototherapy agents with both high photosensitization and photothermal conversion efficiencies. Among the newly developed multifunctional agents, the ones with one or two 3-dicycanovinylindan-1-one (IC) moieties as the acceptors attract much more attention, due to their long-wavelength excitation and emission, as well as high phototherapy efficacies. Therefore, in this review, the latest advancement of multifunctional agents based on IC acceptor is summarized. Especially, we focus on the structure-property relationships of the agents, as well as their biomedical application in anti-tumor therapy or image-guided therapy. Our perspective on the further future development of this field is also discussed to conclude.

Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study.

Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28-1.59; P = 6.66 × 10-11), ovarian cysts (OR = 1.36, 95% CI 1.20-1.55; P = 1.57 × 10-6), AUB (OR = 1.41, 95% CI 1.20-1.66; P = 3.01 × 10-5), and endometriosis (OR = 1.43, 95% CI 1.27-1.70; P = 2.21 × 10-7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.

A biodegradable semiconducting polymer phototherapeutic agent for safe cancer phototherapy.

Combined photodynamic therapy (PDT) and photothermal therapy (PTT) not only effectively reduce the hypoxic resistance to PDT, but also overcome the heat shock effect to PTT. However, the residual phototherapeutic agents still produce reactive oxygen species (ROS) to damage normal tissue under sunlight after treatment, which induces undesirable side effects to limit their biomedical application. Herein, a facile strategy is proposed to construct a biodegradable semiconducting polymer p-DTT, which is constructed by thieno[3,2-b]thiophene modified diketopyrrolopyrrole and (E)-1,2-bis(5-(trimethylstannyl)thiophen-2-yl)ethene moieties, to avoid the post-treatment side effects of phototherapy. Additionally, p-DTT exhibits strong photoacoustic (PA) for imaging, as well as good ROS production capacity and high photothermal conversion efficiency for synergistic PDT and PTT, which has been confirmed by both in vitro and in vivo results. After phototherapy, p-DTT could be gradually oxidized and degraded by endogenous ClO-, and subsequently lose ROS production and photothermal conversion capacities, which can guarantee the post-treatment safety, and address above key limitation of traditional phototherapy.

Dual/Multi-Modal Image-Guided Diagnosis and Therapy Based on Luminogens with Aggregation-Induced Emission.

The combination of multiple imaging methods has made an indelible contribution to the diagnosis, surgical navigation, treatment, and prognostic evaluation of various diseases. Due to the unique advantages of luminogens with aggregation-induced emission (AIE), their progress has been significant in the field of organic fluorescent contrast agents. Herein, this manuscript summarizes the recent advancements in AIE molecules as contrast agents for optical image-based dual/multi-modal imaging. We particularly focus on the exceptional properties of each material and the corresponding application in the diagnosis and treatment of diseases.

Reliability and validity analyses of the postoperative comfort scale for patients with lung cancer undergoing endoscopic surgery and an evaluation of patient comfort.

BACKGROUND: Lung cancer is one of the most common malignant tumours that threaten human health globally. Radical resection under thoracoscopic guidance has been accepted as the major therapeutic option for treating lung cancer clinically. However, the procedure still has some adverse impacts on the comfort of patients following thoracoscopic surgery. OBJECTIVE: To analyse the reliability and validity of the postoperative comfort scale for patients with lung cancer undergoing endoscopic surgery and to evaluate patient comfort. METHODS: With 210 patients with lung cancer undergoing endoscopic surgery as the participants, this study was performed to assess the reliability and validity of the postoperative comfort scale for patients with lung cancer undergoing endoscopic surgery, with the assessment performed by eight experts. RESULTS: The postoperative comfort scale included 28 items and consisted of four dimensions (physiological, psychological, socio-cultural and environmental). The total Cronbach's alpha coefficient of the scale was 0.851, and the split-half reliability coefficient was 0.875. Meanwhile, the content validity index (CVI) was 0.875∼1, and the scale-level average CVI was 0.99. The Chi-square/degree-of-freedom ratio of construct validity was 2.844, suggesting a good model-fitting. Furthermore, the overall average score of patient comfort was 3.72 ± 0.57, with scores ranging between 3.59 ± 0.71 and 3.83 ± 1.06 across all four dimensions, with the lowest score in the physiological dimension. CONCLUSION: The postoperative comfort scale has good reliability and validity and can be applied for the postoperative comfort assessment of patients undergoing endoscopic surgery for lung cancer. Overall, the degree of patient comfort in this assessment was moderate, meaning targeted measures may be required to further improve patient comfort, especially in the physiological dimension.

Novel MSH2 and TSC2 variants in a Chinese family with Lynch syndrome and their synergistic impact in urothelial carcinoma.

Lynch syndrome, an autosomal dominant hereditary disease arising from mutations in mismatch repair genes, is linked to the development of multiple tumor types, notably colorectal cancer, endometrial carcinoma and upper urinary tract urothelial carcinoma. In this study, we present the case of a young patient diagnosed with upper urinary tract urothelial carcinoma, notable for a familial history of diverse malignancies. By employing genetic analysis, we verified the presence of Lynch syndrome within the family and detected novel variants, MSH2 p.A604D and TSC2 p.C738Y, utilizing NGS technology. Subsequently, we conducted validation experiments to assess the pathogenicity of the MSH2 and TSC2 variants. We illustrated that the MSH2 variant can result in diminished MSH2 expression, compromised mismatch repair function, and induce resistance to cisplatin in urothelial carcinoma. Furthermore, we substantiated the promotional impact of the identified TSC2 variant on urothelial carcinoma, encompassing proliferation, invasion, and migration. Significantly, we found that the MSH2 p.A604D variant and TSC2 p.C738Y variant synergistically enhance the promotion of urothelial carcinoma.

Crosstalk between Endothelial Cells and Tumor Cells: A New Era in Prostate Cancer Progression.

Prostate cancer stands as one of the most prevalent malignancies afflicting men worldwide. The tumor microenvironment plays a pivotal role in tumor progression, comprising various cell types including endothelial cells, tumor-associated fibroblasts, and macrophages. Recent accumulating evidence underscores the indispensable contribution of endothelial cells to prostate cancer development. Both endothelial cells and tumor cells release a multitude of factors that instigate angiogenesis, metastasis, and even drug resistance in prostate cancer. These factors serve as regulators within the tumor microenvironment and represent potential therapeutic targets for managing prostate cancer. In this review, we provide an overview of the crucial functions of endothelial cells in angiogenesis, metastasis, and drug resistance, and their prospective therapeutic applications in combating this disease.

Tumor blood vessel in 3D reconstruction CT imaging as an risk indicator for growth of pulmonary nodule with ground-glass opacity.

OBJECTIVE: Despite the vital role of blood perfusion in tumor progression, in patients with persistent pulmonary nodule with ground-glass opacity (GGO) is still unclear. This study aims to investigate the relationship between tumor blood vessel and the growth of persistent malignant pulmonary nodules with ground-glass opacity (GGO). METHODS: We collected 116 cases with persistent malignant pulmonary nodules, including 62 patients as stable versus 54 patients in the growth group, from 2017 to 2021. Three statistical methods of logistic regression model, Kaplan-Meier analysis regression analysis were used to explore the potential risk factors for growth of malignant pulmonary nodules with GGO. RESULTS: Multivariate variables logistic regression analysis and Kaplan-Meier analysis identified that tumor blood vessel diameter (p = 0.013) was an significant risk factor in the growth of nodules and Cut-off value of tumor blood vessel diameter was 0.9 mm with its specificity 82.3% and sensitivity 66.7%.While in subgroup analysis, for the GGO CTR < 0.5[C(the maximum diameter of consolidation in tumor)/T(the maximum diameter of the whole tumor including GGO) ratio], tumor blood vessel diameter (p = 0.027) was important during the growing processes of nodules. CONCLUSIONS: The tumor blood vessel diameter of GGO lesion was closely associated with the growth of malignant pulmonary nodules. The results of this study would provide evidence for effective follow-up strategies for pulmonary nodule screening.

Stemness maintenance of stem cells derived from human exfoliated deciduous teeth (SHED) in 3D spheroid formation through the TGF-ß/Smad signaling pathway.

Mesenchymal stem cells (MSCs) have shown great potential as important therapeutic tools for dental pulp tissue engineering, with the maintenance and enhancement of their stemness being crucial for successful therapeutic application in vivo and three-dimensional (3D) spheroid formation considered a reliable technique for enhancing their pluripotency. Human exfoliated deciduous tooth stem cells (SHED) were cultured in a low attachment plate to form aggregates for five days. Then, the resulting spheroids were analyzed for pluripotent marker expression, paracrine secretory function, proliferation, signaling pathways involved, and distribution of key proteins within the spheroids. The results indicated that 3D spheroid formation significantly increased the activation of the transforming growth factor beta (TGF-ß)/Smad signaling pathway and upregulated the secretion and mRNA expression levels of TGF-ß, which in turn enhanced the expression of pluripotency markers in SHED spheroids. The activation of the TGF-ß/Smad signaling pathway through 3D spheroid formation was found to preserve the stemness properties of SHED. Thus, understanding the mechanisms behind pluripotency maintenance of SHED culture through 3D spheroid formation could have implications for the therapeutic application of MSCs in regenerative medicine and tissue engineering.

Using information criteria to select smoothing parameters when analyzing survival data with time-varying coefficient hazard models.

Analyzing the large-scale survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program may help guide the management of cancer. Detecting and characterizing the time-varying effects of factors collected at the time of diagnosis could reveal important and useful patterns. However, fitting a time-varying effect model by maximizing the partial likelihood with such large-scale survival data is not feasible with most existing software. Moreover, estimating time-varying coefficients using spline based approaches requires a moderate number of knots, which may lead to unstable estimation and over-fitting issues. To resolve these issues, adding a penalty term greatly aids estimation. The selection of penalty smoothing parameters is difficult in this time-varying setting, as traditional ways like using Akaike information criterion do not work, while cross-validation methods have a heavy computational burden, leading to unstable selections. We propose modified information criteria to determine the smoothing parameter and a parallelized Newton-based algorithm for estimation. We conduct simulations to evaluate the performance of the proposed method. We find that penalization with the smoothing parameter chosen by a modified information criteria is effective at reducing the mean squared error of the estimated time-varying coefficients. Compared to a number of alternatives, we find that the estimates of the variance derived from Bayesian considerations have the best coverage rates of confidence intervals. We apply the method to SEER head-and-neck, colon, prostate, and pancreatic cancer data and detect the time-varying nature of various risk factors.

microRNA-1-3p and T-synthase mRNA have high diagnostic efficacy on intestinal mucosal barrier dysfunction in patients with severe acute pancreatitis.

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that can be complicated by intestinal mucosal barrier dysfunction (SAP&IBD). The current study sought to examine the diagnostic efficacy of miR-1-3p and T-synthase mRNA in SAP&IBD patients. First, SAP patients were assigned to SAP&IBD and SAP groups. Serum miR-1-3p expression and T-synthase mRNA expression patterns in peripheral blood B lymphocytes were measured using RT-qPCR. Pearson tests, ROC curve analysis, and multivariate logistic regression were used to analyze the correlation between miR-1-3p/T-synthase mRNA and clinical data, their diagnostic efficiency, and independent risk factors for SAP&IBD patients, respectively. The results showed that serum miR-1-3p in the SAP&IBD group was elevated, and T-synthase mRNA expression in peripheral blood B lymphocytes was diminished. Additionally, serum miR-1-3p expression in SAP&IBD patients was negatively correlated with T-synthase mRNA expression, and positively correlated with their Ranson score, CRP, IL-6, DAO, and D-Lactate levels. Meanwhile, T-synthase mRNA level was negatively correlated with IL-6, DAO, and D-Lactate levels. Both, serum miR-1-3p, T-synthase mRNA, and their combination were found to exhibit diagnostic efficiency for SAP&IBD patients, and were independently associated with IBD in SAP patients. Collectively, our findings suggest that miR-1-3p and T-synthase serve as independent risk factors for SAP&IBD patients and can aid the diagnosis of IBD in SAP patients.