The effects of robot-assisted laparoscopic surgery with Trendelenburg position on short-term postoperative respiratory diaphragmatic function.

OBJECTIVE: To study how Pneumoperitoneum under Trendelenburg position for robot-assisted laparoscopic surgery impact the perioperative respiratory parameters, diagrammatic function, etc. METHODS: Patients undergoing robot-assisted laparoscopic surgery in the Trendelenburg position and patients undergoing general surgery in the supine position were selected. The subjects were divided into two groups according to the type of surgery: robot-assisted surgery group and general surgery group. ① Respiratory parameters such as lung compliance, oxygenation index, and airway pressure were recorded at 5 min after intubation, 1 and 2 h after pneumoperitoneum. ② Diaphragm excursion (DE) and diaphragm thickening fraction (DTF) were recorded before entering the operating room (T1), immediately after extubation (T2), 10 min after extubation (T3), and upon leaving the postanesthesia care unit (T4). ③ Peripheral venous blood (5 ml) was collected before surgery and 30 min after extubation and was analyzed by enzyme-linked immunosorbent assay to determine the serum concentration of Clara cell secretory protein 16 (CC16) and surfactant protein D (SP-D). RESULT: ① Compared with the general surgery group (N = 42), the robot-assisted surgery group (N = 46) presented a significantly higher airway pressure and lower lung compliance during the surgery(P < 0.001). ② In the robot-assisted surgery group, the DE significantly decreased after surgery (P < 0.001), which persisted until patients were discharged from the PACU (P < 0.001), whereas the DTF only showed a transient decrease postoperatively (P < 0.001) and returned to its preoperative levels at discharge (P = 0.115). In the general surgery group, the DE showed a transient decrease after surgery(P = 0.011) which recovered to the preoperative levels at discharge (P = 1). No significant difference in the DTF was observed among T1, T2, T3, and T4. ③ Both the general and robot-assisted surgery reduced the postoperative serum levels of SP-D (P < 0.05), while the robot-assisted surgery increased the postoperative levels of CC16 (P < 0.001). CONCLUSION: Robot-assisted laparoscopic surgery significantly impairs postoperative diaphragm function, which does not recover to preoperative levels at PACU discharge. Elevated levels of serum CC16 after surgery suggest potential lung injury. The adverse effects may be attributed to the prolonged Trendelenburg position and pneumoperitoneum during laparoscopic surgery.

Psoralen inhibits the proliferation and promotes apoptosis through endoplasmic reticulum stress in human osteosarcoma cells.

INTRODUCTION: Psoralen is a main active component of Psoralea corylifolia Linn. (Leguminosae). Psoralen has been reported to show antitumor effects and activity to accelerate osteoblastic proliferation. Nevertheless, the antitumor mechanism of psoralen in osteosarcoma has never been elucidated. The current study is aimed to investigate the therapeutic function of psoralen in human osteosarcoma cells and its potential regulatory mechanism. MATERIAL AND METHODS: Effects of psoralen (0-70 µg/mL) on the viability of two osteosarcoma cell lines cultured for 48 h was evaluated by MTT assays. The concentration of IC10 (8 µg/mL for MG-63 cells and 9 µg/mL for U2OS cells) was regarded to be a non-cytotoxic dose selected as the working concentration in the subsequent experiments. Effects of psoralen on cell proliferation for 48 h was assessed by colony formation assays. Flow cytometry analyses were performed to measure cell cycle and apoptosis. RT-qPCR and Western blotting were carried out to assess RNA expression and protein levels of endoplasmic reticulum (ER) stress associated factors. RESULTS: Psoralen inhibited osteosarcoma cell viability (IC50 25 µg/mL for MG-63 cells and IC50 40 µg/mL for U2OS cells) in a dose-dependent manner and growth inhibition rate reached the highest level when cells were treated with 70 µg/mL psoralen. Psoralen induced cell cycle arrest in the G0/G1 phase and promoted apoptosis of both MG-63 and U2OS cells. The treatment of psoralen resulted in an increase in ATF-6 and CHOP protein levels as well as a decrease in Bcl-2 protein level, indicating that cell apoptosis induced by psoralen was associated with ER stress. Treatment with 4-PBA, the ER stress inhibitor, attenuated the ability of psoralen to promote apoptosis of MG-63 and U2OS cells. CONCLUSIONS: Psoralen showed growth-inhibitory effects in osteosarcoma cells, and induced apoptosis via the ER stress pathway, which might be a potential drug to suppress the development of osteosarcoma.

Effects of tacrolimus on IFN-γ signaling in keratinocytes: possible mechanisms by which tacrolimus affects IFN-γ-dependent skin inflammation.

Interferon-gamma (IFN-γ) signaling in keratinocytes plays an important role in IFN-γ-induced skin inflammation. A novel tacrolimus topical ointment has shown remarkable efficacy in treating skin inflammation. This study explored the mechanism of tacrolimus-modulated IFN-γ signal transduction in HaCaT keratinocytes and the effects of tacrolimus on IFN-γ-associated cytokine production in HaCaT cells. Tacrolimus down-regulated the recombinant human IFN-γ (rhIFN-γ)-induced expression of IFN-γ receptor α (IFN-γRα). The IFN-γ induced expression of phosphorylated Janus kinase 2 (pJAK2) and phosphorylated signal transducer and activator of transcription-1 (pSTAT-1) was also inhibited by tacrolimus. Tacrolimus up-regulated the IFN-γ-induced expression of suppressor of cytokine signaling-1 (SOCS-1). Tacrolimus was also demonstrated to down-regulate IFN-γ-induced the secretion of chemotactic factor CXCL-8 and the expression of intercellular adhesion molecule-1 and human leucocyte antigen HLA-DR. The findings in this work indicate that the direct effects of tacrolimus on IFN-γ signaling in keratinocytes may contribute to its therapeutic efficacy as a topical ointment in the treatment of IFN-γ-dependent skin inflammation.