RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer

PURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m(2) every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m(2) daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade >= 3 related treatment-emergent adverse events (TEAEs). The most common grade >= 3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged

Bushenhuoluo Decoction improves polycystic ovary syndrome by regulating exosomal miR-30a-5p/ SOCS3/mTOR/NLRP3 signaling-mediated autophagy and pyroptosis

Abstract Background Polycystic ovary syndrome (PCOS) is a frequent and complicated endocrine disease that remains a major reason for infertility. Bushenhuoluo Decotion (BSHLD) has been validated to exhibit curative effects on PCOS. This study was aimed to explore the potential mechanism underlying the therapeutic action of BSHLD. Methods PCOS rat model was induced by dehydroepiandrosterone (DHEA). Serum hormone and cytokines levels and ovarian pathological alterations were measured to assess ovarian function. Exosomes (Exos) were identified by Transmission electron microscopy and Nanoparticle Tracking Analysis. RT-qPCR, Western blotting, immunohistochemical staining, and immunofluorescence staining were performed to detect molecule expressions. Proliferation and pyroptosis of granulosa cells (GCs) were evaluated by CCK-8 and flow cytometry, respectively. The binding relationship between miR-30a-5p and suppressor of cytokine signaling 3 (SOCS3) was verified by dual luciferase reporter and RIP assays. Results BSHLD treatment improved serum hormone abnormality, insulin sensitivity, and ovarian morphologic changes of PCOS rats. Moreover, BSHLD treatment restrained the excessive autophagy and pyroptosis in ovarian tissues of PCOS rats. Moreover, BSHLD reduced the expression of miR-30a-5p in serum, serum-derived Exos, and ovarian tissues, thus inhibiting autophagy and NLRP3-mediated pyroptosis in GCs. Mechanistically, SOCS3 was proved as a target of miR-30a-5p and could activate mTOR/P70S6K pathway to repress autophagy. The inhibitory effect of miR-30a-5p deficiency on autophagy and pyroptosis of GCs was attenuated by rapamycin. Conclusion Collectively, BSHLD suppressed autophagy and pyroptosis to improve POCS by regulating exosomal miR-30a-5p/SOCS3/mTOR signaling

Decoupled Unipolar Hysteresis Current Control for Single-Phase Grid-Tied Inverter Without Current Zero-Crossing Distortion

A digital controlled unipolar hysteresis current control strategy applied to the single-phase grid-connected inverter is studied in the paper. In view of the problem of current zero-crossing distortion in the traditional unipolar hysteresis current control based on finite state machines (FSM), a new unipolar hysteresis current control strategy based on current decoupling is proposed. By introducing a virtual zero-sequence current, the single-phase full-bridge inverter is decoupled into two independent half-bridge inverter units, which are controlled by two bipolar hysteresis current control loops under the constraints of a finite state machine. Therefore, the operation rules of the FSM ensure the frequency doubling output of the unipolar modulation, and the virtual two-phase decoupled current eliminates the zero-crossing distortion problem of inverter output current. Finally, the effectiveness and feasibility of the proposed method were verified by building a 1kW single-phase full-bridge grid-connected inverter in the laboratory

A regular sampling method based on the immediate mode for improving the stability of inverters

The shadow mode-based regular sampling methods are usually used in the digital control of power inverters, which introduce a control delay of one and a half sampling periods. The control delay affects the closed loop bandwidth and the stability of dc–ac inverters. Recently, regular sampling methods based on the immediate mode is emerging and helpful for reducing the digital control delay. When employing the immediate mode, the induced vertical crossings may arouse the duty-cycle loss and dead-band effect during the modulation process, which deteriorate the normal operation of the inverters. Although the duty-cycle loss can be avoided by forcing the PWM signal to flip at the occurrence of vertical crossings, the introduced dead bands still exist. Thus, this paper investigates the phenomenon of vertical crossings and proposes a control algorithm composed of predicting the occurrence of vertical crossings and compensating the dead-band effect for regular sampling methods based on the immediate mode. Finally, experimental results on a single-phase dc–ac inverter prototype are provided to compare the efficacy of different approaches