ABSTRACT
Stroke is the second leading cause of death worldwide,and oxidative stress plays a crucial role.Celastrol exhibits strong antioxidant properties in several diseases;however,whether it can affect oxidation in cerebral ischemic-reperfusion injury(CIRI)remains unclear.This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms.Here,we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2(Nrf2).Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry,we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4(Nedd4)and then released Nrf2 from Nedd4 in astrocytes.Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI,which was significantly blocked by celastrol.Furthermore,by inhibiting oxidative stress and astrocyte activation,celastrol effectively rescued neurons from axon damage and apoptosis.Our study uncovered Nedd4 as a direct target of celastrol,and that celastrol exerts an antioxidative effect on as-trocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.
ABSTRACT
Due to the impact of COVID-19, the online problem-based learning (PBL) teaching mode was first implemented based on the curriculum integration of basic medicine and clinical medicine in our university in 2020. A total of 357 eight-year program clinical medicine students from three grades participated in the online PBL courses. The students have had related skills and knowledge of integration curriculum, and the teachers have carried out sufficient analysis of learning situation, preparation of software and hardware, as well as teaching design. Teachers and students has communicated with each other smoothly and cooperated closely through the Tencent Conference software platform, therefore this teaching mode has gained better feedback among students, with higher satisfaction of courses and significantly improved students' learning enthusiasm. The curriculum integration has laid the foundation for the case design and application of online PBL teaching, while the success of online PBL teaching has also reflected the original intention of curriculum integration reform.
ABSTRACT
Objective:To evaluate the effects of ultrasound-guided quadratus lumborum block (QLB) on acute pain after total hip arthroplasty.Methods:A retrospective study was conducted of the 36 patients with hip osteoarthritis who had undergone selective one-side total hip arthroplasty under total intravenous anesthesia (TIVA) from January 2019 to January 2020. According to whether additional QLB was used or not they were divided into 2 equal groups ( n=18). The control group of 10 males and 8 females with an age of 60.5±9.4 years used mere TIVA while the QLB group of 7 males and 11 females with an age of 53.6±12.7 years used TIVA plus QLB. All patients accepted patient-controlled intravenous analgesia (PCIA) postoperatively. The 2 groups were compared in terms of visual analogue scale (VAS) at rest and during exercise and IL-6 level at 24 h postoperation, consumption of opioids and postoperative incidence of nausea and vomiting. Results:There were no significant differences between the 2 groups in their preoperative general data, indicating they were compatible ( P>0.05). The VAS scores at rest and during exercise in the QLB group (0.3 ± 0.5 and 0.8 ± 0.6) were significantly lower than in the control group (2.1 ± 0.7 and 2.7 ± 0.5), the IL-6 level in the former[40.9 (30.5, 56.3) pg/mL] was significantly lower than in the latter[165.0 (82.5, 276.5) pg/mL], the intraoperative total consumptions of sufentanil[6 (6, 7) μg] and remifentanil[1,370 (1,200, 1,485) μg] in the former were significantly lower than in the latter[35 (30, 40) μg and 1, 910 (1, 805, 2, 000) μg], and the postoperative incidenceof nausea and vomiting[27.8%(5/18)] in the former was significantly lower than in the latter[77.8%(14/18)] (all P<0.05). Conclusions:Ultrasound-guided quadratus lumborum block can effectively relieve acute pain in patients after total hip arthroplasty. It can suppress stress-related inflammatory factors, reduce consumption of opioids and incidence of postoperative nausea and vomiting.
ABSTRACT
Objective To observe the effect of dexmedetomidine on patients′ inflammation during CPB and protective effect on kidney and liver. Methods 60 cases undergoing cardiac valve replacement under CPB were randomly divided into NS group and Dex group. Blood samples were taken before induction , before ascending aorta blocked, end of CPB, 24, 48 and 72 hours after operation. The serum level of HMGB-1, TNF-α, IL-6, BUN, Cr and ALT are tested. Blood WBC and N% are also counted. Results WBC, N% and HMGB-1, TNF-α, IL-6, BUN, Cr in Dex group significantly decreased at time point T2 ~ T6 (P < 0.05) compared with NS group. But ALT in Dex group only decreased at time point T 2 and T5 compared with NS group (P < 0.05). Conclusion Dexmedetomidine can significantly decrease inflammatory factor during CPB and improve renal function after surgery.
ABSTRACT
Objective To investigate the effect of Ulinastatin preconditioning on hyperthermia induced rat skeletal muscle injury and the possible mechanism. Methods Cultured skeletal muscle cells were divided into 7 groups: control group (Group C), as normal culture; hyperthermia treated group (Group H), in which cells were exposed to 42℃for 2 hours then transfered to normal culture; ulinastatin preconditioned group (Group U), which were only preconditioned 1 hour by the final concentration of ulinastatin at 1 250 U/mL; and four different concentration of ulinastatin preconditioned+hyperthermia treated groups (Group Ⅰ, Ⅱ, Ⅲ, Ⅳ), in which cells were preconditioned 1 hour by the final concentration of ulinastatin at 312 , 625, 1250, 2 500 U/mL, respectively. And then, all the four groups were exposed to 42℃for 2 hours. MTT assay and LDH leakage were performed to study the cytotoxicity. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) formation were measured to reflect the activity of antioxidase. Results Compared with Group H, MTT value in ulinastatin preconditioned group in GroupⅠ, Ⅱ,Ⅲ, Ⅳsignificantly increased (P0.05). Conclusion Ulinastatin preconditioning may have protective effect against hyperthermia induced skeletal muscle injury and it may be related to its ability of inhibiting radical production and promoting radical scavenging.