Role of immune checkpoint inhibitors combined with chemotherapy in recurrent drug-resistant gestational trophoblastic neoplasia: Four case reports and literature review.

BACKGROUND: Multiple studies have confirmed that programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) is widely expressed in gestational trophoblastic neoplasia (GTN) tissues. Therefore, immune checkpoint inhibitors may be an option for the treatment of recurrent and drug-resistant GTN. CASE: Four patients with recurrent or drug-resistant GTN who were treated with PD-1/PD-L1 checkpoint inhibitor agents combined with chemotherapy were reported. The mean age of recurrence was 45.8 years (35-56 years), including three cases of choriocarcinoma (CC) and one case of invasive mole (IM). International Federation of Gynecology and Obstetrics (FIGO) prognosis score: ≤6 (low risk) in one case, 7-12 (high risk) in one case, ≥13 (very high risk) in two cases. There were two cases of lung metastasis and one case of vulvar and inguinal lymph node metastasis. One of the four patients underwent total hysterectomy and one patient underwent resection of lung metastases. All the four patients received comprehensive treatment of immunotherapy combined with chemotherapy after relapse, among which one patient achieved complete response (CR), two patients achieved partial response (PR), and one patient developed progressive disease (PD). Three patients who achieved PR or CR were maintained by single agent immunotherapy after combination therapy, and there was no disease recurrence during follow-up. One patient with PD also achieved CR after using salvage chemotherapy after recurrence, and there was no disease recurrence during follow-up. During the treatment, four patients had different degrees of immune-related adverse reactions, all of which were grade I-II, and no severe adverse reactions were found. CONCLUSION: Immune checkpoint inhibitors combined with chemotherapy has an impressive therapeutic effect on recurrent or drug-resistant GTN with mild adverse reactions, which can be used as a treatment option for such patients. However, due to the lack of large sample data support, the specific time and treatment course of its use, long-term use of adverse reactions and whether it affects fertility function remain to be solved.

Process Optimization for Robotic Ultrasonic Strengthening of Aviation Blade Surfaces Based on Intelligent Compliance Control.

In order to enhance the automation level and achieve high precision in the ultrasonic strengthening of aviation blade surfaces, this study focuses on investigating the intelligent control strategy and optimizing the machining parameters for robotic ultrasonic surface strengthening. By designing an intelligent compliance control method, the end-effector can achieve the compliant output of contact force. The fuzzy PID control method is used to optimize the regulation performance of the compliant force control system. This compliance control strategy enables the optimization of the compliance device, effectively improving the static and dynamic characteristics of the compliance controller. Based on this, an experimental method (RSM) is designed to analyze the interaction effects of contact force, feed rate, and repetition times on the surface quality of the blade. The optimal combination of robotic strengthening parameters is determined, providing a practical reference for the application of robotic compliance control in the ultrasonic strengthening of aviation blade surfaces.

Adaptive Anti-Disturbance Control for a Class of Uncertain Nonlinear Systems With Composite Disturbances.

High-precision and safety control in face of disturbances and uncertainties is a challenging issue of both theoretical and practical importance. In this article, new adaptive anti-disturbance control schemes are proposed for a class of uncertain nonlinear systems with composite disturbances, including additive disturbances, multiplicative actuator faults, and implicit disturbances deeply coupled with system states. Both the cases with known and unknown control/fault directions are investigated. By properly fusing the techniques of disturbance observers and adaptive compensation, it is shown that all closed-loop signals are globally uniformly bounded and the tracking error converges to zero asymptotically, no matter the control/fault directions are known or not. In the case of known directions, the proposed control scheme, for the first time, guarantees asymptotic tracking and L ∞ tracking performance simultaneously in face of disturbances and actuator faults. Moreover, novel Nussbaum functions and a contradiction argument are introduced, which allow the system to have multiple unknown nonidentical control directions and unknown time-varying fault direction. Simulation results illustrate the effectiveness of the proposed control schemes.

Effects of activating GABAB1 receptor on proliferation, migration, invasion and epithelial-mesenchymal transition of ovarian cancer cells.

OBJECTIVE: This study aimed to explore the effects of activating GABAB1 receptor by baclofen on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ovarian cancer cells. RESULTS: One hundred µmol/L, 200 µmol/L and 300 µmol/L were selected as low, medium and high baclofen concentrations respectively. Cells were divided into four groups: Control, 100 µmol/L, 200 µmol/L and 300 µmol/L. Compared with the control group, the viability, colony formation, migration and invasion of SKOV3 cells were inhibited, and the apoptosis of SKOV3 cells were enhanced significantly at 200 µmol/L and 300 µmol/L baclofen. Moreover, they changed significantly with the increase of baclofen concentration. Compared with the control group, the expression of E-cadherin and GABAB1 increased and the N-cadherin expression decreased significantly in 200 µmol/L and 300 µmol/L groups. Higher concentration of baclofen induced higher expression of E-cadherin and lower expression of N-cadherin. CONCLUSION: Baclofen inhibited the proliferation, cloning, migration, invasion and EMT of ovarian cancer cells by activating GABAB1 receptor. These results might contribute a lot to clarify the role and possible mechanism of GABAB1 receptor in ovarian cancer.