Introduction: Pain is still severe after singleport video-assisted thoracoscopic (SPVAT) lung wedge resection. We observed the effect of single-injection thoracic paravertebral block (TPB) via the intrathoracic approach for analgesia after SPVAT lung wedge resection. Methods: Sixty patients undergoing SPVAT lung wedge resection were randomly divided into a control group and an observation group. All patients underwent TPB via the intrathoracic approach at the T4 level with a scalp needle before closing the chest. The patients in the observation group received 20 ml 0.375% ropivacaine at the T4 level, and the patients in the control group received 20 ml of 0.9% saline. A patient-controlled intravenous analgesic (PCIA) pump with sufentanil was attached to all patients after surgery. The sufentanil consumption and number of PCIA presses in the first 24 h after surgery were recorded. The visual analogue scale (VAS) scores (during rest and coughing) were recorded at 6 h, 12 h, 24 h, and 36 h after surgery. The incidence of adverse reactions after surgery were recorded. Results: The sufentanil consumption in the observation group was significantly lower than that in the control group (34.2 ± 1.9 lg vs. 52.3 ± 2.3 lg; P \ 0.001). The VAS score at 6, 12, and 24 h after surgery, the incidence of adverse reactions after surgery in the observation group were significantly lower than those in the control group (all P \ 0.05). The number of PCIA presses in the observation group was significantly lower than that in the control group [0 (0-0) times vs. 3 (2-4) times, P \ 0.001]. Conclusions: Single-injection TPB via the intrathoracic approach under thoracoscopic direct vision is easy to perform and can effectively alleviate postoperative pain after SPVAT lung wedge resection, with fewer adverse reactions. Trial Registration: ChiCTR2000034726.

Background We observed the feasibility and effectiveness of multi-injection thoracic paravertebral block (TPB) via the intrathoracic approach under thoracoscopic direct vision for analgesia after thoracoscopic-laparoscopic esophagectomy (TLE). Methods Sixty patients undergoing TLE were randomly divided into a control group and an observation group. All patients underwent TPB via the intrathoracic approach at the three levels of T2, 5, and 8 with a scalp needle before closing the chest. The patients in the observation group received 10 ml 0.375% ropivacaine at each level, and the patients in the control group received 10 ml of 0.9% saline at each level. A patient-controlled intravenous analgesic (PCIA) pump with sufentanil was attached to all patients after surgery. The sufentanil consumption, number of PCIA presses and use of rescue analgesia in the first 24 h after surgery were recorded. The visual analogue scale (VAS) scores (rest and coughing) were recorded at 2 h, 6 h, 12 h, 24 h, and 48 h after surgery. The duration of postoperative hospital stay, active cough rate, first ambulation, and the incidence of adverse reactions after surgery was recorded. Results The sufentanil consumption in the observation group was significantly lower than that in the control group (34.7 ± 1.9 µg vs. 52.1 ± 2.1 µg; P < 0.001). The VAS score at each postoperative time point, number of PCIA presses, use of rescue analgesia, and the incidence of adverse reactions in the observation group were significantly lower than those in the control group. The postoperative active cough rate of patients in the observation group was significantly higher than those in the control group, and the times of the first ambulation after surgery and postoperative hospital stay in the observation group were significantly shorter than those in the control group (all P < 0.05). Conclusions Multi-injection TPB via the intrathoracic approach under thoracoscopic direct vision is easy to perform and can effectively alleviate postoperative pain after TLE with fewer adverse reactions and contributing to improved postoperative recovery.

Background: Sevoflurane can protect organs from ischemia-reperfusion (IR) injury, but the mechanism is still unclear. is a liver-specific microRNA (miRNA) and regulates liver function.Therefore, this study aims to elucidate the relationship between the protective effect of sevoflurane and miR-122 in liver IR injury.Methods: Wistar rats were divided into the following groups: sham, IR, IR + sevoflurane, IR + miR-122 antagomir, and IR + miR-122 antagomir + sevoflurane. Hematoxylin and eosin (H&E) staining and Suzuki score were used to evaluate the pathological damage of the liver. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 in the serum and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in the liver homogenate supernatant were detected by using the corresponding kit. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and flow cytometry was applied to evaluate the apoptosis of liver tissues. The expression of nuclear factor E2-related factor 2 (Nrf2), miR-122, p53, and HO-1 in liver tissue was evaluated by using immunohistochemistry, qRT-PCR, and western blot as needed.Results: Compared to the IR group, the sevoflurane post-treatment or miR-122 antagomir groups showed improved liver injury, decreased Suzuki score, inhibited the levels of AST, ALT, LDH, MDA, NO, TNF-α, IL-1β, and IL-6, increased levels of SOD, IL-10, and inhibited hepatocyte apoptosis. Regarding the molecular mechanism, sevoflurane post-treatment fostered the expression of HO-1, promoted the transport of Nrf2 from cytoplasm to the nucleus, and decreased the expression of miR-122 and p53. The combined use of miR-122 antagomir and sevoflurane enhanced the protective effect of miR-122 antagomir in liver injury in IR rats.Conclusions: Sevoflurane protected the liver from IR damage by regulating the miR-122/Nrf2/HO-1 pathway.

The G1 restriction point is critical for regulating the cell cycle and is controlled by the retinoblastoma protein (Rb) pathway (CDK4/6-cyclin D1-Rb-p16/ink4a). Selective CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib have been approved by US FDA as single agent or in combination with endocrine therapy to treat patients with HR+/Her2- breast cancer. Here, we disclose the preclinical development of CS3002 and its characterization as a novel CDK4/6 inhibitor with unique kinase inhibition spectrum. Similar to the three approved CDK4/6 inhibitors, CS3002 is highly selective for and potent against CDK 4 and 6, a feature that is expected to overcome the toxicity issues of pan-CDK inhibitors. Cell-based assays confirmed the biological activities of CS3002 by showing anti-proliferative effect, significant Rb phosphorylation inhibition, and G1 cell cycle arrest in a set of Rb-positive cancer lines. Furthermore, CS3002 showed excellent in vivo activity as a single agent, and in combinations with either endocrine therapy (fulvestrant) or PD-1 blockade (CS1003) in a set of tumor models, together with desirable ADME/PK and safety profile. CS3002 was further tested against 196 kinases in a Carna panel. In addition to CDK4 and CDK6, FLT3 and TRKA were also potently inhibited with IC50 values &lt;50nM. To this end, CS3002 demonstrated high activity in cell lines harboring NTRK1 fusion that were otherwise insensitive to CDK4/6 inhibitors. Across a panel of 19 AML cell lines, CS3002 demonstrated a similar sensitivity profile to gilteritinib (an approved FLT-3 inhibitor), but overall higher sensitivity compared to palbociclib. Interestingly, when MCF-7 breast cancer cell line was treated continuously with CS3002 in vitro, the emergence of drug-resistance was much delayed compared to treatment with palbociclib or abemaciclib. Given the encouraging preclinical properties as well as the unique potential in allowing indication expansion and delaying drug resistance to CDK4/6 inhibition, CS3002 is selected for clinical exploration in a Phase 1 study for advanced solid tumors (NCT04162301). Citation Format: Juan Zhang, Liang Tang, Zhenhu Li, Liang Lu, Yuanwu Bao, Zhaoxiang Ren, Jingshu Ma, Yaling Huang, Zhaobing Xu, Yuanfeng Xia, Charles Z. Ding, Lihong Hu, Shuhui Chen, Archie N. Xie, Xinzhong Jon Wang. CS3002, a novel CDK4/6 inhibitor with unique kinase inhibition spectrum which may expand indications beyond breast cancer and delay acquired drug resistance [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4844.