TIM-3 regulates the proliferation by BDNF-mediated PI3K/AKT axis in the process of endometriosis.

BACKGROUND: T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) initially discovered on the surface of Th1 cells, negatively regulates immune responses and mediates apoptosis of Th1 cells. An increasing number of studies have since shown that TIM-3 is crucial in the genesis and development of immune diseases, cancers, and chronic infectious illnesses. However, the effect of TIM-3 on endometriosis is still unknown. METHODS: Quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry were used to measure TIM-3 levels in endometriosis. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, colony-forming, Transwell® migration, Matrigel® invasion, and flow cytometry assays were used to explore the function of TIM-3 in vitro, and xenograft experiments in nude mice were used to assess its role in vivo. According to the RNA seq, brain-derived neurotrophic factor (BDNF) was screened. The involvement of specific proliferation-related signaling molecules was determined by transfecting a plasmid and adding an inhibitor in vivo and in vitro. RESULTS: TIM-3 mRNA and protein expression levels were significantly higher in eutopic and ectopic endometrial tissues than in normal endometrial tissues. By examining the effects of TIM-3 overexpression and knockdown on cell proliferation, migration, and invasion in vitro, and lesions formation in vivo, we found that the expression of TIM-3 was positively correlated with cell proliferation and clone formation in vitro, as well as lesions growth in nude mice. By adding the phosphatidylinositol 3 kinase/protein kinase B(PI3K/AKT) pathway inhibitor LY294002 and knocking down PI3K, we further verified that TIM-3 promotes proliferation in vivo and in vitro via the PI3K pathway. By transfecting the plasmid into ESC cells and gave inhibitors to endometriotic rats models, we tested that TIM-3 regulates the proliferation by BDNF-mediated PI3K/AKT axis. CONCLUSION: TIM-3 can promote the proliferation of endometriosis by BDNF-mediated PI3K/AKT axis in vivo and in vitro, which may provide a new therapeutic target for the treatment of endometriosis.

Development and validation of a deep learning algorithm for pattern-based classification system of cervical cancer from pathological sections.

Background: Multi-center research has demonstrated that adopting Silva's pattern-based classification system (SPBC) enhances the clinical prognosis and facilitates hierarchical management of patients with endocervical adenocarcinomas (EAC). However, inconsistencies in SPBC can arise due to variations in pathologists' experience levels. Thus, the implementation of standardized decision-making tools becomes crucial to enhance the practicality of SPBC in clinical diagnosis and treatment. Methods: We enrolled a total of 90 patients with EAC in this study, of which 63 were assigned to the training group, and the remaining 27 were allocated to the validation group. To create and validate the prediction models for SPBC, we utilized a deep learning system (DLS) and calculated the area under the receiver operating characteristic curve (AUC). Results: In Silva pattern classification, ResNet50 achieved an average accuracy of 74.36% (63.64% for pattern A, 55.56% for pattern B, and 89.47% for pattern C respectively). Moreover, in test set, ResNet50 achieved an AUC of 0.69 for pattern A, 0.58 for pattern B, and 0.91 for pattern C. Conclusions: We successfully established a DLS for SPBC, which holds the potential to aid pathologists in accurately classifying patients with EAC.

Cost-effectiveness of Insulin Degludec Versus Insulin Glargine in Insulin-naive Chinese Patients With Type 2 Diabetes.

PURPOSE: The goal of this study was to investigate the long-term economic outcomes of insulin degludec versus insulin glargine use in Chinese patients with type 2 diabetes mellitus (T2DM) whose oral antidiabetic drugs did not provide sufficient glycemic control. METHODS: A published and validated Chinese diabetes health policy model, which reflects Chinese T2DM epidemiologic profiles, was used to assess the lifetime economic outcomes of microvascular and macrovascular complications and mortality. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables for estimating the quality-adjusted life-years (QALYs) and costs, as well as incremental cost-effectiveness ratios. The analysis was conducted from the perspective of Chinese health care service providers. One-way and probabilistic sensitivity analyses were performed. FINDINGS: Compared with insulin glargine, insulin degludec was associated with 0.0053 QALY at an additional cost of $3278 in our simulated cohort. This outcome resulted in an incremental cost-effectiveness ratio of insulin degludec over insulin glargine of $613,443 per QALY gained. The one-way sensitivity analyses indicated that the results were sensitive to several model inputs. IMPLICATIONS: Insulin degludec is unlikely to be cost-effective compared with insulin glargine for Chinese patients with T2DM whose disease is inadequately controlled with oral antidiabetic drugs.

Cost-effectiveness analysis of different rescue therapies in patients with lamivudine-resistant chronic hepatitis B in China.

BACKGROUND: Several rescue therapies have been used in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these therapies is unclear. The object of the current analysis was to evaluate the lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant CHB. METHODS: A Markov model was developed to simulate the clinical course of patients with LAM-resistant CHB. From the perspective of Chinese health care, a lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic or clinical LAM-resistant CHB entered the model, and the beginning health state was LAM-resistant CHB without other complications. The transition probabilities, efficacy and resistance data for each rescue therapy as well as the costs and utility data were estimated from the literature. The discount rate (3%) utilized for costs and benefits. Sensitivity analyses were used to explore the impact of uncertainty on the results. RESULTS: In LAM-resistant HBeAg-positive and HBeAg-negative CHB cohorts, TDF monotherapy and combination therapy were on the efficiency frontier for both positive and negative populations. Compared with no treatment, the use of combination therapy cost an additional $6,531.7 to gain 1 additional quality-adjusted life year (QALY) for HBeAg-positive patients and $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy for HBeAg-positive patients, shows greater increase in QALYs but higher incremental cost-effectiveness ratio (ICER) in comparison with combination therapy. In probabilistic sensitivity analyses, combination therapy was the preferred option for health care systems with limited health resources, such as Chinese health care system. CONCLUSION: In Chinese patients with LAM-resistant CHB, combination therapy is a more cost-effective option than the competing rescue therapies.