Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic protein that plays a key role in promoting cell survival in multiple myeloma, acute myeloid leukemia and non-Hodgkin lymphoma. MCL-1 is highly expressed in a variety of hematological malignancies, which is one of the important factors leading to poor prognosis and chemoresistance in patients with hematological malignancies. Therefore, MCL-1 is an important therapeutic target for hematological malignancies. Several MCL-1 inhibitors have entered clinical trials, including S63845, AZD5991, S64315, AMG-176, and AMG-397. The treatment plans used for hematological malignancies include monotherapy with MCL-1 inhibitors, as well as combination therapy with B cell lymphoma 2 inhibitors or immunomodulatory drugs, all indicating that MCL-1 inhibitors may be a breakthrough point for targeted treatment of hematological malignancies.

Objective To detect the apoptosis effects of dioscin in HepG2 cells and its possible anti-hepatocellular carcinoma mechanisms.Methods HepG2 human hepatocellular carcinoma cells were exposed to 0.25,0.5,1,2,4,6,or 8 μmol/L dioscin,and cell proliferation was measured via MTT assay.The half-maximal inhibitory concentration(IC50)was calculated with the software.A scratch test was used to analyze cell migration ability.Western blot was employed to evaluate the expression of apoptosis and Wnt/β-catenin-pathway-related proteins.Results Compared with the control group,the dioscin-treated HepG2 cells'proliferation was significantly more inhibited,and the inhibition increased in a time-and dose-dependent manner(P＜0.01).HepG2 cells showed morphological characteristics of apoptosis after they were treated with 1 μmol/L or 2 μmol/L dioscin.The scratch test indicated that the migration distance of HepG2 cells was remarkably reduced when treated with dioscin.In the Western blot experiment,the expression levels of Caspase-3 and cleaved Caspase-3 were visibility up-regulated,while those of Bcl-2 and β-catenin were significantly down-regulated when the cells were treated with dioscin for 24 h(P＜0.05,P＜0.01).When LiCl reagent was added to the HepG cells to activate the Wnt/β-catenin signaling pathway,the expression levels of Wnt1 and β-catenin were remarkably increased compared with those of the control group(P＜0.01).Compared with the LiCl group,the LiCl+DIO group's expression of Wnt1,β-catenin,and GSK-3β was significantly decreased(P＜0.01).Conclusions DIO can promote the apoptosis of HepG2 cells by inhibiting β-catenin protein expression and thereby down-regulating the Wnt/β-catenin signaling pathway.This inhibits apoptosis-related gene Bcl-2 expression,which leads to the induction of cell apoptosis.Therefore,DIO can have an anti-hepatocellular carcinoma effect.

Objective To conduct a scoping review of virtual reality motor sensing exercise in the elderly with dementia,so as to identify the types of intervention,outcome indicators,evaluation tools and application effects of virtual reality motor sensing exercise and provide guidance for future research.Methods A literature search was performed in the PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,and CMB databases to identify relevant studies.The search period is from the establishment of databases to October 15,2023.The included studies were summarized and analyzed.Results A total of 18 articles were included in this study,including 14 randomised controlled trials,one class-experimental study and three mixed studies involving a total of 1,054 elderly dementia patients.The types of virtual reality motor sensing exercise included motor sensing interactive games,interactive bicycle riding,remote game exercise,Wii Fit exercise and virtual reality environment exercise.The outcome indicators involve 4 aspects of physical indicators,psychological indicators,cognitive function and quality of life.Conclusion Virtual reality motor sensing exercise is feasible and effective in the elderly with dementia.However,large sample and high-quality randomized controlled trials are still needed in the future to verify the feasibility and application effect of virtual reality exercise in the elderly with dementia,so as to provide evidence-based basis for formulating the best exercise intervention program for the elderly with dementia.

Objective:To evaluate the effect of trehalose on oxygen-glucose deprivation and restoration (OGD/R) injury in H9C2 cells and the role of solute carrier family 7 member 11- (SLC7A11)-glutathione peroxidase 4 (GPX4) signaling pathway.Methods:Well-grown H9C2 cells were divided into 4 groups ( n=24 each) by the random number table method: control group (group C), OGD/R group (group O), OGD/R+ trehalose group (group OT) and OGD/R+ trehalose+ erastin group (group OTE). The cells were normally cultured in group C. In O, OT and OTE groups, the DMEM medium was replaced with EBSS medium, the cells were exposed to 5% CO 2-95% N 2 in an incubator at 37 ℃ for 6 h, and then the medium was replaced with DMEM medium supplemented with 6% fetal bovine serum to restore oxygen and glucose supply for 24 h. In group OT, trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. In group OTE, the SLC7A11 inhibitor erastin at a final concentration of 10 μmol/L was added at 8 h before oxygen-glucose deprivation, and trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. The cell viability, lactic dehydrogenase (LDH) activity, contents of glutathione (GSH), malondialdehyde (MDA) and iron, and reactive oxygen species (ROS) levels were measured at 24 h of restoration of oxygen and glucose supply. The expression of SLC7A11, GPX4, long-chain fatty acyl coenzyme A synthetase 4 (ACSL4), and ferritin heavy chain 1 (FTH1) was detected by Western blot. The structure of the mitochondrial morphology was observed with a transmission electron microscope. Results:Compared with group C, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS level were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group O ( P<0.05). Compared with group O, the cell viability and GSH content were significantly increased, the LDH activity, contents of MDA and iron, and ROS level were decreased, the expression of SLC7A11, GPX4 and FTH1 was up-regulated, and the expression of ACSL4 was down-regulated in group OT ( P<0.05). Compared with group OT, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS levels were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group OTE ( P<0.05). Conclusions:Trehalose can inhibit ferroptosis by activating the SLC7A11-GPX4 signaling pathway, thereby attenuating OGD/R injury in H9C2 cells.

Objective:To measure the anatomical parameters of the simulated low tibial tunnel of posterior cruciate ligament (PCL) based on knee CT images so as to provide clinical reference for accurate location of the tunnel.Methods:The CT images of 201 healthy knee joints collected at Department of Orthopedics, The Second Hospital of Lanzhou University from June 2016 to September 2021 were used for simulation of the PCL low tibial tunnel. The anatomical parameters of the tibial tunnel were measured using the RadiAnt DICOM Viewer. The primary measures included the angle between tibial plateau and tibial tunnel (ATPT) and the perpendicular distances from the tibial tunnel entrance and exit point to the tibial plateau (L1 and L2). The secondary measures included the angle between tibial plateau and posterior slope (PSA), the angle between tibial anatomical axis and central line of tibial tunnel (ATAA), the angle between posterior tibial slope line and the central line of tibial tunnel (APST), the anterior and posterior diameter of tibial plateau (APD), the length of posterior tibial slope (LPTS), and the length of tibial tunnel (LTT). The measurement results were analyzed according to the body height (divided into 3 groups: a 1.00 to 1.60 m group, a 1.61 to 1.70 m group, and a ≥1.71 m group) and gender using the software IBM SPSS 26.Results:The primary measures: ATPT was 37.0°±4.5°, and L1 and L2 were respectively (57.8±7.4) mm and (34.5±3.3) mm. The secondary measures: PSA 128.1°±5.4°, ATAA 52.7°±4.1°, APST 89.1°±5.9°, APD was (32.9±2.6) mm, LPTS (20.5±2.4) mm, and LTT (40.9±5.7) mm. After grouping by gender, there was no significant difference in PSA between men and women ( P>0.05) while there were significant differences in the other indexes between men and women ( P<0.05). After grouping by body height, there was no significant difference in ATPT, PSA, APST or ATAA between the 3 groups (1.00 to 1.60 m group, 1.61 to 1.70 m group and ≥1.71 m group) ( P>0.05) while there were significant differences in L1, L2, APD, LPTS and LTT between the 3 groups ( P<0.05). Conclusions:Based on the knee CT images, the primary measures of PCL low tibial tunnel are as follows: the angle between tibial plateau and tibial tunnel is 37.0°±4.5°, and the perpendicular distances from the tibial tunnel entrance and exit point to the tibial plateau are (57.8±7.4) mm and (34.5±3.3) mm, respectively. Gender and body height are the important factors influencing the above measurement outcomes.

Deepening the ideological and political construction of curriculum and carrying out the fundamental task of cultivating people with morality are the important requirements of education reform and talent cultivation in the new era. Microbiology Experiment is an important basic course and core practice course of Bioengineering, Pharmaceutical Engineering, Food Science and Engineering, et al. In order to give full play to the education function of Microbiology Experiment, this article deeply developed the ideological elements contained in the curriculum referring to the guidelines for the construction of ideological and political courses in institutions of higher education. And the article explored the ideological and political reform of Microbiology Experiment from three aspects: teaching content reform, teaching method innovation and improvement of teachers' ideological and political construction ability. Strive to integrate the value shaping, knowledge transference and ability training, cultivate high-quality professionals with firm ideals and beliefs.
Curriculum ; Humans ; Universities

Objective:To study the dosimetric differences and short-term efficacy between intracavitary/interstitial brachytherapy (IC/ISBT) and conventional intracavitary brachytherapy (ICBT).Methods:Forty-five patients with locally advanced cervical cancer were treated with IC/ISBT and ICBT. Points A (A 1, A 2), D 90%, D 100%, organs at risk, and the doses of bladder, colon, rectum and small intestine were calculated and the short-term efficacy was observed between two groups. Results:Point A dose was significantly improved in IC/ISBT compared with ICBT ( P<0.05). The D 90% and D 100% in IC/ISBT were significantly higher than those in ICBT (both P<0.05). After brachytherapy, IC/ISBT could obtain a significantly larger increase in target dose when residual tumor diameter was ≥3 cm compared with ICBT ( P<0.05). The D 2cm 3 and D 0.1cm 3 of bladder, rectum, colon and small intestine did not significantly differ between IC/ISBT and ICBT (all P>0.05). The 1-, 3-and 6-month clinical efficacy did not significantly differ between two technologies (all P>0.05). Conclusion:During brachytherapy for locally advanced cervical cancer (residual tumor diameter ≥3 cm), IC/ISBT significantly increases the doses of target area and point A without increasing the dose of organs at risk or lowering the short-term clinical efficacy, which has significant dosimetric advantages.

Objective To investigate the dynamic changes in intestinal alpha-defensin-5 (RD-5),beta-defensin-2 (BD-2) mRNA after acute liver failure(ALF),and to explore their role in ALF.Methods A total of 60 C57BL5 mice were divided into 4 groups by means of random number table method:normal control group,ALF group,E.coli via gavage group and ALF + E.coli via gavage group.Intraperitoneal injection of D-galactosamine (500 mg/kg) and lipopolysaccharide(10 μg/kg) to make the model,in addition,ALF mice were fed with E.coli,and the observation time was 6 hours,12 hours,and 24 hours after modeling,and each time point had 6 specimens.Real-time PCR was used to test the RD-5 mRNA and BD-2 mRNA levels in the ileum tissue.Results The levels of RD-5 and BD-2 showed dynamic change in the experiment of ALF.Compared with the levels of RD-5 and BD-2(11.25 ±0.74,23.86 ±0.39) of the normal control group,the levels of RD-5 and BD-2 in ALF group and E.coli via gavage group increased at 6 hours after modeling(14.19 ±0.39,26.79 ± 0.36 and 12.57 ± 0.68,26.45 ± 0.85),and the differences were significant(all P＜0.05);at 12 hours after modeling,the RD-5 and BD-2 reached to the maximum concentration(15.76 ±0.33,29.10 ± 0.61 and 12.90 ± 0.96,27.42 ± 0.71),and the differences were statistically signi-ficant (all P ＜ 0.05).The degree of elevation of BD-2 was higher than RD-5.Later,they gradually declined.Conclusions RD-5 and BD-2 may play an important role in the pathogenesis of intestinal endotoxemia in experimental ALF.

Objective To study the short-term efficacy of computed tomography (CT)-guided iodine-125(125I) radioactive seed implantation in the treatment of hypoxic tumors.Methods Twenty-two patients treated with 125I radioactive seed implantation in our department from 2014 to 2016 were divided into hypovascular tumor group (hypoxic group,n =12) and hypervascular tumor group (non-hypoxic group,n=10) based on the hemodynamics of solid tumor evaluated by color Doppler ultrasound.The enhanced CT images were loaded to the three-dimensional particle implantation planning system for preoperative planning.After 125I radioactive seed implantation,the D90 for target volume was verified to be 106-128 cGy.Treatment outcomes were evaluated according to the World Health Organization criteria at 1-3 months after surgery.Results In all the patients,the overall response rate was 82％ at 3 months after surgery.There were no significant differences in response (complete response + partial response) rates at 1,2,or 3 months after surgery between the hypoxic group and the non-hypoxic group (P=0.840,0.696,0.840).Conclusions In the treatment of solid malignant tumor,125I radioactive seed implantation can overcome the resistance of hypoxic tumor to radiotherapy in vitro and achieve satisfactory short-term efficacy.

Objective To investigate the effects of olanzapine combined with metacognitive training on social cognition and insight of schizophrenic patients.Methods One hundred twenty patients with schizophrenia were randomly divided into two groups. All patients received four week treatment. The study gr oup received olanzapine combined metacognitive training treatment and the control group only used olanzapine treatment. The positive and negative symptoms scale (PANSS), the Insight and Treatment Attitude Questionnaire (ITAQ), the Beck Cognitive Insight Scale (BCIS) and Faux Pas Recognition Task (FPRT) were assessed at baseline and after four weeks of treatment. Result There was no statistically significant difference in the scores of all battery between two groups before treatment (P>0.05). the scores of total PANSS and subscales, ITAQ, BCIS and FPRT were statistically significant between study and control groups (P<0.05).After 4 weeks of treatment,the total PANSS scores and subscales scores were significantly lower in the study group than in the control group (P<0.05). The ITAQ score, self-reflection factor of BCIS, composite index and FPRT scores were significantly higher in the study group than in the control group (P<0.05). The difference in self-certainty of BCIS difference was not statistically significant(P>0.05).Differences of the remaining scales were statistically significant(P<0.05). Conclusion Olanzapine combined with metacognitive training has a significant effect on the social cognitive dysfunction in schizophrenic patients,improving the patient's insight and enhancing the social function.