Objective To investigate the impacts of butorphanol(BUT)on the biological activity and chemotherapy drug resistance of osteosarcoma cells by regulating the forkhead box protein O3(FOXO3)-forkhead box protein M1(FOXM1)signal axis.Methods CDDP resistant MG-63 cells(MG-63/CDDP)treated with 2.0 μmol/L cisplatin(CDDP)were separated into control group(MG-63/CDDP cells were treated with 0.05％DMSO medium),BUT group(MG-63/CDDP cells were treated with 40 μg/mL BUT),JY-2 group(MG-63/CDDP cells were treated with 100 μmol/L FOXO3-FOXM1 inhibitor JY-2),and BUT+JY-2 group(MG-63/CDDP cells were treated with 40 μg/ml BUT and 100 μmol/L JY-2).CCK8 method was applied to detect MG-63/CDDP cell activity.Flow cytometry was used to detect apoptosis in MG-63/CDDP cells.The Transwell method was applied to detect the migration and invasion of MG-63/CDDP cells;Western blot was applied to detect the expression of autophagy proteins and proteins related to the FOXO3-FOXM1 signaling pathway.Results Compared with MG-63 cells,the IC50(20.56±2.52μmol/L vs(0.97±0.10μmol/L)of MG-63/CDDP cells was increased,and the differences was statistically significant(q=19.017,P<0.05),and the optimal concentration of 1 μmol/L CDDP was selected for subsequent experiments.Compared with the control group,the A value(0.43±0.05 vs 0.68±0.06),numbers of cell migration(63.63±7.58 vs 114.56±10.57)and invasion(43.38±4.58 vs 79.56±8.48),and the levels of autophagy-related protein Beclin1(0.31±0.05 vs 0.62±0.07)and microtubule-associated protein light chain 3(LC3)-Ⅱ/Ⅰ proteins(0.51±0.08 vs 0.98±0.11)in the BUT group were reduced(q=6.763～9.591,all P<0.05),the apoptosis rate(28.57％±3.14％vs 8.67％±1.46％),the levels of FOXO3(0.72±0.08 vs 0.33±0.04)and FOXM1(1.22±0.15 vs 0.70±0.08)proteins were increased(q=14.077,10.681,7.493,all P<0.05),however,in the JY-2 group,the A value(0.99±0.13 vs 0.68±0.06),numbers of cell migration(147.59±15.37 vs 114.56±10.57)and invasion(111.83±12.58 vs 79.56±8.48),and the levels of Beclin1(0.94±0.11 vs 0.62±0.07)and LC3-Ⅱ/Ⅰ(1.27±0.13 vs 0.98±0.11)proteins in the JY-2 group were increased(q=4.171～6.012,all P<0.05),the apoptosis rate(4.56％±0.86％vs 8.67％±1.46％),the levels of FOXO3(0.17±0.01 vs 0.33±0.04)and FOXM1(0.46±0.03 vs 0.70±0.08)proteins were reduced(q=5.941,9.505,6.881,all P<0.05),and the differences were statistically significant,respectively.JY-2 reversed the beneficial effects of BUT on MG-63/CDDP cell activity and chemotherapy resistance.Conclusion BUT may regulate the cell activity and CDDP resistance of osteosarcoma cells by activating the FOXO3-FOXM1 signaling pathway.

Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmaco-logical mechanisms of AG underlying the prevention and treatment of ASCVD have not been corrobo-rated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound('old bottle')as a novel drug('novel wine')for the pre-vention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.

Objective:To study the effect of medical social workers combined with ICU diary on the prevention and treatment of post-traumatic stress disorder in ICU traffic accident patients, and to explore the application of continuing nursing services and ICU diary to ICU traffic accident patients.Methods:A total of 47 patients who were admitted to the ICU of Suzhou Science and Technology City Hospital from January to December 2019 due to traffic accidents were selected by convenient sampling method. Twenty-three patients admitted to the hospital in the first 6 months were selected as the control group (before the introduction of medical social workers and ICU diaries) for routine ICU treatment and nursing mode. Twenty-four patients admitted to the hospital in the last 6 months were selected as the experimental group (after the introduction of medical social workers and ICU diaries), and the medical social workers combined with the ICU diary were intervened. The scores of the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were compared between the two groups of patients when they were admitted to the ICU, stayed in the ICU for a week, and transferred out of the ICU. The incidence of post-traumatic stress disorder was evaluated and compared by the scores of the Impact of Event Scale-Revised of the two groups of patients one month after leaving the ICU, three months after leaving the ICU, and six months after leaving the ICU.Results:The scores of SAS in the experimental group were 58.67 ± 7.45, 44.13 ± 5.47 and 39.08 ± 5.52 when they were admitted to the ICU, stayed in the ICU for a week, and transferred out of the ICU, and were 58.17 ± 6.75, 50.87 ± 6.35 and 42.74 ± 4.85, respectively in the control group. There was no statistical difference in the scores of the SAS between the two groups of patients when they were admitted to the ICU ( P>0.05), but there was a time difference between the two groups with time changes and different interventions ( Ftime = 110.98, P<0.01), there were also differences between groups ( Fbetween groups = 5.91, P<0.05). Compared with the control group, the SAS score of the experimental group decreased more significantly( Finteraction = 0.28, P<0.05). The scores of SDS in the experimental group were 57.75 ± 4.06, 45.29 ± 3.39 and 36.63 ± 3.49 when they were admitted to the ICU, stayed in the ICU for a week, and transferred out of the ICU, and were 57.48 ± 2.29, 49.04 ± 5.65 and 43.57 ± 4.07 respectively in the control group. There was no statistical difference in the scores of the SDS between the two groups of patients when they were admitted to the ICU ( P>0.05), but there was a time difference between the two groups of patients with time changes and different interventions ( Ftime = 248.24, P<0.01), there are also differences between groups ( Fbetween groups = 24.39, P<0.05). Compared with the control group, the SDS score of the experimental group decreased more significantly ( Finteraction=10.44, P<0.05). The incidences of post-traumatic stress disorder in the experimental group were 9, 8, 6 cases at one month, three months and six months after leaving the ICU, which were lower than 12, 11, 8 cases in the control group. The generalized estimation equation showed that the difference was statistically significant ( χ2=4.21, P<0.05). Conclusions:The intervention model of medical social workers combined with ICU diary is conducive to the use of ICU diary and the development of continuous nursing, which improves patients′negative emotions and reduces the incidence of post-traumatic stress disorder.

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

In order to make up for the innovation deficiency in the traditional residency training model and the shortcomings of active learning and lifelong learning, evidence-based medicine is introduced into the residency training of dental general practitioners. Theoretical knowledge training of evidence-based medicine is conducted through online course learning. PICO mode is used to conduct evidence-based analysis of clinical cases under the guidance of the instructor, so that trainees can get familiar with the process of evidence-based analysis. Students can finally design and complete the application cases of evidence-based medicine, and teachers give evaluation guidance. Through this process, students can learn and master the knowledge of evidence-based medicine step by step, thus obtaining better teaching results.

Objective:To explore the effect of moxibustion pretreatment on bone marrow suppression in cancer patients after chemotherapy, so as to provide a basis for clinical nursing.Methods:From May 2019 to May 2020, we selected 70 cancer patients who met the criteria in the Oncology Department of a ClassⅢ Grade A hospital in Xuzhou City, Jiangsu Province by convenient sampling. There were 65 patients who finally completed the trial including moxibustion pretreatment group ( n=20) , moxibustion group ( n=22) , and control group ( n=23) . All three groups received regular chemotherapy. Patients in moxibustion pretreatment group received moxibustion 7 days before the start of chemotherapy, once a day, for 14 days; patients in moxibustion group were treated with moxibustion at the beginning of chemotherapy, once a day, for 7 days; control group carried out conventional chemotherapy. We compared the white blood cell count, neutrophil count, incidence and degree of bone marrow suppression, and the use of recombinant human granulocyte colony stimulating factor among the three groups. Results:The white blood cell and neutrophil counts of the three groups were compared between the groups and at different times, and the differences were statistically significant ( P<0.05) . The incidences of bone marrow suppression on the seventh and fourteenth day after chemotherapy of the three groups of patients were compared between the groups and at different times with statistical differences ( Wald χ2groups=6.628, P=0.036; Wald χ2times=43.018, P<0.001) . A total of 7, 14 days after chemotherapy, there were statistical differences in the use of recombinant human granulocyte colony stimulating factor in patients among the three groups ( P<0.05) . Conclusions:Moxibustion pretreatment can stabilize the white blood cell and neutrophil counts of cancer patients after chemotherapy, reduce the incidence of bone marrow suppression, the degree of bone marrow suppression as well as the use of recombinant human granulocyte colony stimulating factor.

Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors (ICIs) have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity. Particularly, the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S. Food and Drug Administration (FDA)-approved anti-programmed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies. However, the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity. Indeed, the cyclic guanosine monophosphate-adenosine monophosphate synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS‒STING‒TBK1) axis is now appreciated as the major signaling pathway in innate immune response across different species. Aberrant signaling of this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection and cancers. In this perspective, we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS‒STING‒TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy. Meanwhile, highlights on the clinical candidates, limitations and challenges, as well as future directions in this field are also discussed. Further, small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.

Objective:To explore the status quo of meaning of life in patients undergoing radical mastectomy and analyze the influencing factors.Methods:The convenient sampling method was used to select 302 patients with breast cancer who were treated in 2 Class Ⅲ Grade A hospitals in Zhenjiang from June 2019 to February 2020 as research objects. The general data questionnaire, Chinese version of Meaning in Life Questionnaire (C-MLQ) , Health-related Hardiness Scale (HRHS) and Cognitive Reassessment Strategy Scale were used to investigate them.Results:A total of 315 questionnaires were issued and 302 valid questionnaires were collected.The total score of C-MLQ of 302 patients undergoing radical mastectomy was (31.65±6.71) , the total score of HRHS was (92.59±5.68) and the total score of Cognitive Reassessment Strategy Scale was (16.23±5.04) .The results of multiple linear regression analysis showed that cognitive reassessment, postoperative time, health-related hardiness and its control dimension, family monthly income, gender, radiotherapy and chemotherapy were the influencing factors of meaning of life in patients undergoing radical mastectomy ( P<0.05) , which explained 85.8% of the variation in meaning of life. Conclusions:The meaning of life of patients undergoing radical mastectomy is at a medium low level. Clinical medical staff should take effective intervention measures to improve cognitive reassessment ability of patients, so that they can have correct cognition of the disease. They should also encourage them to face the disease actively and bravely and strengthen their own health-related hardinessin order to improve the meaning of life.

Objective To assess the efficiency and safety of mycophenolate mofetil (MMF) in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO). Methods Twenty-seven patients with MS or NMO were selected, and the patients were divided into 2 groups:MMF group (MMF combined with glucocorticoid treatment group, 10 cases) and glucocorticoid group (only glucocorticoid treatment group, 17 cases). There were 5 cases with MS and 5 cases with NMO in MMF group. There were 13 cases with MS and 4 cases with NMO in glucocorticoid group. The therapeutic efficacy 6 months after treatment, expanded disability status scale (EDSS) before treatment and 6 months after treatment, and annualized relapse rate (ARR) were compared; and the safety was observed. Results There was no statistical difference in efficacy rate 6 months after treatment between MMF group and glucocorticoid group: 9/10 vs. 11/17, P>0.05. The EDSS scores 6 months after treatment in MMF group and glucocorticoid group were significantly lower than those before treatment: (2.41 ± 2.05) scores vs. (3.40 ± 2.05) scores and (1.17 ± 0.92) scores vs. (2.38 ± 1.28) scores, and there were statistical differences (P<0.05), particularly for the patients with MS. The ARR 6 months after treatment in MMF group was significantly lower than that before treatment: 0 time/year vs. 0.75 times/year, and there was statistical difference (P<0.05). The difference of ARR before and after treatment in MMF group was significantly higher than that in glucocorticoid group: 0.75 times/year vs.- 0.46 times/year, and there was statistical difference (P<0.01), particularly for the patients with MS. Only 1 female patient had myalgia when taking higher dosage of MMF, and the symptom tended to relieve after the dosage was reduced. Conclusions MMF is effective in the treatment of MS and NMO. MS can improve the neurological function and reduce the recurrence of the disease;and the safety is high.