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Objective To compare the effect of spinal anesthesia and general anesthesia(GA) on postoperative sleep quality in elderly patients undergoing hip surgery. Methods In this prospective cohort-based study, patients with hip fracture, aged ≥65 years were divided into 2 groups according to the anesthesia method: combined spinal plus epidural anesthesia(CSEA) group and GA group(n=69 each) from November 2019 to August 2020. All patients received the same perioperative pain management. Subjective sleep quality was assessed by the sleep diaries recording sleep quality, total sleep time, and number of awakenings. The Objective sleep quality was assessed by sleep tracker recording total sleep time(TST), rapid-eye-movement(REM) time, light sleep time and deep sleep time. Numeric Rating Scales(NRS) were used to assess the intensity of postoperative pain. Results Compared with CSEA group, the Sleep Quality Score and deep sleep time were significant lower(P＜0.05), and the number of awakenings(P＜0.05) was significant higher in GA group in the intraday night of surgery. Conclusions Compared with CSEA group, sleep disruption is more severe in the GA group at the intraday night of the patients with hip fracture.

Combination therapy could significantly improve the therapeutic effect of tumors. However, due to the lack of reasonable integration of different treatment modes, it is difficult to maximize the effect of combination treatment. To solve this problem, by adjusting the dosage of NH4F/NaOH, we developed NaTmF4:0.5%Er3+@NaLuF4 upconversion nanoparticles with strong near-infrared luminescence. On this basis, nanocarriers (USFH-CI) encapsulated with high-loading (33.35%) Fe-(acac)3, wrapped by human serum albumin, and grafted with cinnamic aldehyde (CA) and the IR780 photosensitizer were constructed. The dense extracellular matrix (ECM) in tumor tissues prevented the drug from diffusing into the tumors. Once USFH-CI nanocarriers were delivered to the tumor area, CA pH-responsively released H2O2, which promoted photothermal therapy (PTT) and photodynamic therapy (PDT) of IR780 driven by upconversion luminescence. A large number of reactive oxygen species (ROS) were generated, which led to the disintegration of the ECM and penetration into the tumors. Then, abundant Fe3+ consumed GSH to generate ample GSSG and Fe2+, which enhanced the sensitivity of tumor cells to oxidative stress, thus leading to the accumulation of lipid peroxide (LPO) and finally inducing ferroptosis. At the same time, substantial H2O2 and Fe2+ triggered off the Fenton-like reaction, releasing affluent free radicals. Beyond that, PTT of IR780 further promoted the Fenton-like reaction, and the generation of ROS was amplified. Free radicals generated in the process of ferroptosis destroyed heat shock protein produced by PTT, which solved the self-protection of cancer cells against heat. In situ ROS generation by the PTT/PDT of IR780 and the Fe2+ Fenton-like reaction further promoted the accumulation of LPO and ferroptosis as well as deep penetration, which maximized the effect of combination treatment and achieved a high tumor inhibition rate (84.71%). Also, there was negligible damage to normal tissues with good tumor targeting and digestive metabolism. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a new therapy for treating cancer with less toxicity, high selectivity, good cooperativity, and repetitive usability. However, keloid treatment by PDT is mainly focused on clinical appearance, and few studies have been conducted on the mechanisms of PDT. In this study, key factors of the classical mitochondrial apoptosis signaling pathway were measured to assess the effect of a new PDT photosensitizer (p1). A specific inhibitor of caspase-8 (Z-IETD-FMK) was also used to verify the possible mechanisms. Twelve samples were obtained from 12 patients (six with keloids and six without) selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January to December 2020. After cell culture, fibroblasts were divided into 13 groups. The morphology of fibroblasts in each group was observed by microscopy. Cell activity was measured by cell counting kit-8, and cell apoptotic morphology was observed by TUNEL staining. The reactive oxygen species (ROS) relative value was measured by a ROS test kit. The expression levels of key mitochondrial factors (caspase-3, caspase-8, cytochrome-c, Bax, and Bcl-2) were assessed by western blot, and mRNA expression of caspase-3 and caspase-8 was measured by RT-qPCR. We showed that p1 had a satisfactory proapoptotic effect on keloid fibroblasts by increasing the expression of ROS, caspase-3, caspase-8, and cytochrome-c, and decreasing the Bcl-2/Bax ratio; however, this effect was partially inhibited by Z-IETD-FMK, indicating that caspase-8 may be one of the p1's targets to achieve the proapoptotic effect. [ABSTRACT FROM AUTHOR]

Proliferation is an important characteristic of life, and many signaling pathways participate in this complicated process. The MAPK/Erk pathway is a classic pathway in cell proliferation. In this study, expression levels of key factors in the MAPK/Erk pathway were measured to assess the proliferation level among normal skin, physiological scar, and keloid tissue. Thirty patients were selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January 2019 to December 2020. Histological appearance and fiber tissue content were observed by Hematoxylin and eosin staining and Masson staining. Expression levels of key factors in the MAPK/Erk pathway (ATF2, c-Jun, c-Myc, p38 and STAT1) and relative proteins (HIF-1α and PCNA) in tissues were detected by immunohistochemistry and analyzed as the percentage of positively stained cells in both the tissue epidermis and dermis. Western blot was used for quantitative analysis of the above factors. In results, keloid tissue showed a significantly higher fiber and less cell content. In the immunohistochemical result, higher expression of key factors was observed in the epidermis than in the dermal layer, and the expression of all factors was increased remarkably in keloid tissue. In western blot analysis, all factors (except STAT1) showed higher expression in keloid tissue. In our former research, keloid showed similar apoptosis level as physiological scar and normal skin. On combining our former conclusion and results in this study, an imbalance condition between the high proliferation level and normal apoptosis level may lead to the growth characteristics of keloid. [ABSTRACT FROM AUTHOR]

To improve the treatment efficiency of ferroptosis and accurately monitor the therapy process, we developed small-sized upconversion nanoparticles (UCNPs) by a simple one-step solvothermal method. On this basis, a facile strategy is reported to construct mesoporous SiO2-coated UCNPs as the nanocarrier to load dual drugs of MnO2 and methylene blue (MB) photosensitizer for hypoxic tumor theranostic. Due to the components of high charge elements, the synthetic NaErF4:Yb,Gd,Eu@mSiO2/MnO2/MB@FA (UPSMF/MB, FA = folic acid) exhibited radiosensitization function. Emitting strong red upconversion luminescence (UCL) excited the encapsulated MB to initiate photodynamic therapy (PDT). In addition, UPSMF/MB released green UCL imaging in vivo, so as to trace drug distribution and achieve accurate theranostic. In tumor microenvironment, the loaded MnO2 possessed catalase-like (CAT) catalytic activity, which could effectively decompose excessive H2O2 into O2, thus alleviating hypoxia in the tumor area and promoting PDT and radiotherapy (RT) to generate reactive oxygen species (ROS). Furthermore, MnO2 had excellent glutathione peroxidase (GPx)-like activity, which could effectively decompose intracellular over-expressed glutathione (GSH), thus causing lipid peroxide (LPO) accumulation and inducing ferroptosis. In situ ROS generation by PDT and RT further promoted the accumulation of intracellular LPO. Cytotoxicity assay revealed that the apoptosis rate of UPSMF/MB promoted by RT and PDT was 79.76%, which was 46% higher than that of solo ferroptosis induced by UPSMF. Notably, in vivo results illustrated that the tumor inhibition rate of UPSMF/MB could be increased to 83.4% under the triple effects of RT, PDT, and ferroptosis with negligible side effects to normal tissues. This work paves a way to enhance the efficacy of ferroptosis-based cancer therapy by associating PDT with RT. [ABSTRACT FROM AUTHOR]