1.Sanguinarine alleviates ulcerative colitis in mice by regulating the Nrf2/NF-κB pathway
Na ZHAO ; Mengdi SHEN ; Rui ZHAO ; Di AO ; Zetan LUO ; Yinliang ZHANG ; Zhidong XU ; Fangtian FAN ; Hailun ZHENG
Journal of Southern Medical University 2024;44(8):1467-1475
Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.
2.Sanguinarine induces ferroptosis of colorectal cancer cells by upregulating STUB1 and downregulating GPX4
Yinliang ZHANG ; Zetan LUO ; Rui ZHAO ; Na ZHAO ; Zhidong XU ; Di AO ; Guyi CONG ; Xinyu LIU ; Hailun ZHENG
Journal of Southern Medical University 2024;44(8):1537-1544
Objective To investigate the effect of sanguinarine(SAN)on proliferation and ferroptosis of colorectal cancer cells.Methods SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC50 of SAN in the two cells.The inhibitory effects of SAN on proliferation,invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays.ROS production in the treated cells was analyzed with flow cytometry,and lipid peroxide production was assessed by detecting malondialdehyde(MDA)level.Glutathione(GSH)levels in the cells were detected,and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4.Results SAN significantly inhibited the proliferation,invasion and migration of SW620 and HCT-116 cells.SAN treatment significantly promoted ROS production,increased intracellular MDA level,and lowered GSH level in the two cells(P<0.05).Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4(P<0.05).Conclusion SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4,which may serve as a new therapeutic target for colorectal cancer.
3.Sanguinarine alleviates ulcerative colitis in mice by regulating the Nrf2/NF-κB pathway
Na ZHAO ; Mengdi SHEN ; Rui ZHAO ; Di AO ; Zetan LUO ; Yinliang ZHANG ; Zhidong XU ; Fangtian FAN ; Hailun ZHENG
Journal of Southern Medical University 2024;44(8):1467-1475
Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.
4.Sanguinarine induces ferroptosis of colorectal cancer cells by upregulating STUB1 and downregulating GPX4
Yinliang ZHANG ; Zetan LUO ; Rui ZHAO ; Na ZHAO ; Zhidong XU ; Di AO ; Guyi CONG ; Xinyu LIU ; Hailun ZHENG
Journal of Southern Medical University 2024;44(8):1537-1544
Objective To investigate the effect of sanguinarine(SAN)on proliferation and ferroptosis of colorectal cancer cells.Methods SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC50 of SAN in the two cells.The inhibitory effects of SAN on proliferation,invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays.ROS production in the treated cells was analyzed with flow cytometry,and lipid peroxide production was assessed by detecting malondialdehyde(MDA)level.Glutathione(GSH)levels in the cells were detected,and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4.Results SAN significantly inhibited the proliferation,invasion and migration of SW620 and HCT-116 cells.SAN treatment significantly promoted ROS production,increased intracellular MDA level,and lowered GSH level in the two cells(P<0.05).Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4(P<0.05).Conclusion SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4,which may serve as a new therapeutic target for colorectal cancer.
5.Construction of evaluation index system of occupational protection competency of nurses in Operating Room
Xiaojun ZHU ; Lei SONG ; Dan ZHOU ; Na KONG ; Xue YANG ; Ao FENG ; Lin ZHAO
Chinese Journal of Modern Nursing 2023;29(19):2562-2568
Objective:To construct the evaluation index system of occupational protection competence of Operating Room nurses based on the competency model.Methods:A research team was established in October 2022 to preliminarily construct an evaluation index system for occupational protection competency of Operating Room nurses through literature retrieval and expert interviews. From November to December 2022, 2 rounds of expert letter consultation were conducted with 23 experts, and the evaluation index system of occupational protection competence of Operating Room nurses was finally established. The enthusiasm of experts was expressed through the effective response rate of the inquiry questionnaire, the degree of expert authority was expressed using the expert authority coefficient, and the degree of coordination of expert opinions was expressed using the Kendall's W coefficient. Results:The effective recovery rates of the questionnaire in 2 rounds of expert consultation were respectively 100.00% (23/23) and 91.30% (21/23), the expert authority coefficients were respectively 0.878 and 0.920, and Kendall's W of the overall index in 2 rounds of letter consultation were respectively 0.239 and 0.312 ( P<0.01). Finally, an evaluation index system of occupational protection competency of Operating Room nurses was formed, including 4 first-level indexes, 12 second-level indexes and 53 third-level indexes. Conclusions:The competency evaluation index system of occupational protection for Operating Room nurses based on competency model is scientific and reasonable, which can provide training ideas for future clinical training practitioners and college educators.
6.Study of the effect of liraglutide on the correlation between NLRP3 inflammasome and non-alcoholic fatty liver disease
Zhuoqi MA ; Na AO ; Nan YANG ; Jing YANG ; Shi JIN ; Cen DU ; Jian DU
Chinese Journal of Hepatology 2022;30(6):624-630
Objective:To observe the effect of liraglutide on the correlation between nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) infl ammasome and nonalcoholic fatty liver disease (NAFLD).Methods:Thirty-nine NAFLD cases (group N) and thirty-nine healthy subjects (group C) were selected from the physical examination center, and their general data were collected to determine the serum levels of NLRP3, IL-1β, and IL-18. The differences and correlations were analyzed between the two sets of indicators. Thirty male SD rats were randomly divided into normal (NC, n=10) and high-fat diet group (HF, n=20). The normal group were fed with normal diet and high-fat diet group were fed with high-fat diet. After 12 weeks of feeding, HF group was randomly divided into HF group ( n=10) and liraglutide group (100L, n=10), and were given 0.5 ml/kg sterile isotonic saline and 100 g/kg liraglutide subcutaneously twice a day, respectively. Four weeks later, serum biochemical indicators, liver NLRP3 infl ammasome protein expression, and infl ammatory cytokine conditions were detected in each group. Statistical analysis was performed using t test, oneway analysis of variance (ANOVA) or χ2 test. Results:There were no statistically signifi cant differences between N and C group in terms of age, gender, diastolic blood pressure, glycosylated hemoglobin, mean platelet volume, erythrocyte distribution width, serum low-density lipoprotein cholesterol (HDL-Ch), total cholesterol, and total bileacid. Compared with group C, group N had elevated systolic blood pressure, body mass index (BMI), fasting blood glucose, blood creatinine, alkaline phosphatase (ALP), NLRP3, interleukin (IL)-1β, IL-18, TG, blood uric acid, γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and white blood cell counts, while HDL-Ch and total bilirubin were depleted than group C, and the difference was statistically significant ( P< 0.05). NLRP3 was positively correlated with systolic blood pressure, BMI, fasting blood glucose, serum creatinine, IL-1β, IL-18, triglycerides, serum uric acid, GGT, ALT, AST, but negatively correlated with total bilirubin and HDL-Ch, and the difference was statistically signifi cant. Compared with NC group, HF group had significantly increased body mass, liver mass, serum biochemical indicators (triglycerides, AST, ALT), liver NLRP3 inflammasome protein expression, and inflammatory cytokines. After treatment with liraglutide, 100L group indicators were signifi cantly decreased when compared to HF group. Conclusion:Compared with healthy subjects, the infl ammation-related indicators, body mass, blood lipids and liver function-related indicators are signifi cantly changed in patients with NAFLD, which is also consistent with the results of rat model study. Liraglutide treatment had improved NAFLD to certain extent in NAFLD rats, so NLRP3 regulation may be one of the mechanisms to improve liver inflammation and steatosis.
7.Influencing factors and etiological characteristics of postoperative multidrug-resistant organism infection in patients with traumatic brain injury
Na ZHANG ; Caihong LIU ; Juan AO ; Huijuan HOU ; Fengjiang ZHANG
Chinese Journal of Modern Nursing 2022;28(8):1002-1007
Objective:To analyze the risk factors and etiological characteristics of multidrug-resistant organism (MDRO) infection after traumatic brain injury, and to explore its nursing countermeasures.Methods:From January 2019 to January 2021, convenience sampling was used to select 478 patients with post-traumatic infection in the First Affiliated Hospital of Zhengzhou University as the research object. The patients' gender, age, underlying diseases, and infection types were collected, and the patients were divided into MDRO infection group ( n=69) and non-MDRO infection group ( n=409) according to whether the pathogen was MDRO. Binary Logistic regression was used to analyze the risk factors of MDRO infection. Results:Logistic regression analysis showed that cerebrovascular disease, malnutrition, history of shock, invasive operation, and combined use of antibiotics were independent risk factors for MDRO infection, and the difference was statistical ( P<0.05) . A total of 516 strains of pathogenic bacteria were detected in the infected samples of 478 patients, of which 386 were target strains, involving 73 strains of MDRO (18.91%) , including 22 strains of Staphylococcus aureus (30.14%) , 14 strains of Pseudomonas aeruginosa (19.18%) , 13 strains of Klebsiella pneumoniae (17.81%) , 11 strains of Escherichia coli (15.07%) , 10 strains of Acinetobacter baumannii (13.70%) , 3 strains of Enterococcus faecalis (4.11%) . The lower respiratory tract was the main site of infection, followed by the urinary tract, wound and upper respiratory tract. Conclusions:Combination of underlying diseases, invasive operation, and combined use of antibiotics all increase the risk of postoperative MDRO infection in patients with traumatic brain injury. Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae are common MDROs. Clinical nurses should strengthen the monitoring of the condition of patients with traumatic brain injury, do a good job of isolation protection, to prevent the occurrence of respiratory system, urinary system and wound infection in patients.
8. Effect of FKBP38 expression on occurrence and development of nonalcoholic fatty liver disease in mice
Min-Yi TANG ; Shuai WANG ; Chao-Feng XING ; Ao-Lu LIU ; Zi-Jian ZHAO ; Yun-Ping MU ; Li-Na WANG ; Fang-Hong LI
Chinese Pharmacological Bulletin 2022;38(4):518-524
Aim To investigate the effects of FKBP38 gene on nonalcoholic fatty liver disease ( NAFLD ) model induced by methionine and choline deficiency j J diet (MCD) in mice.Methods The mutant model of hepatocellular specific deletion of FKBP38 gene was successfully established.The mice were divided into wild-type group ( WT) and homologous knockout group (L-FKBP38 ).Mice were fed with MCD for four weeks to construct NAFLD model.Liver injury was e- valuated by the contents of alanine transaminase (ALT), aspartate transaminase (AST) in the serum samples.We also performed HE staining, examined lipid accumulation by triglyceride (TG) and total cholesterol (CHO) and oil red staining, as well as macrophage infiltration by F4/80 immunohistochemical stai-ning of the liver sections.Fatty acid metabolism-relat ed genes were quantifier] by Quantitative Real-time PCR assays.Results Comparer] with WT group, the levels of ALT, AST, TG and CHO in serum signifi- eantly inereased ( P < 0.05 ) ; liver damage , lipid ac- eumulation, and maerophage infiltration were markedly more severe, and the expressions of fatty aeirl oxidation related genes PPARa, ACOX-1 , CPT-la and SIRT3 markedly rleereaserl ( P < 0.05) in the liver samples of L-FKBP38 group.Conclusions Hepatocellular speeifie deletion of FKBP38 intensifies lipid accumula- tion by inhibiting fatty aeid oxidation in the liver, thus exaeerbating nonaleoholie fatty liver disease.
9. Research progress of dopamine and dopamine receptor in pathogenesis of asthma
Ao Li-Bin LI ; Na WU ; Xue-Ping YAO
Chinese Pharmacological Bulletin 2022;38(1):5-8
Asthma is a common respiratory disease charaeterized by airway inflammation and airway hyperresponsiveness.Dopamine is an important neurotransmitter in human body.In reeent years it has been reported that dopamine reeeptor is expressed in immune eells, type I alveolar eells, airway epithelium and airway smooth muscle, and affects ovalbumin ( OVA )-indueed asthma in animals.This review introduees the role of dopamine in the occurrence and development of asthma from the aspeets of airway inflammation, pulmonary nerve regulation, airway epithelial and smooth muscle abnormalities.
10.Role of ski injury treatment system between the ski resort medical station of Winter Olympics and the nearby medical care hospital.
Yu Ping YANG ; Xiao MA ; Na Yun CHEN ; Yan Fang JIANG ; Xiao Wei ZHANG ; Zhong Wei DING ; Tao LIU ; Ying Fang AO
Journal of Peking University(Health Sciences) 2021;53(3):580-585
OBJECTIVE:
To make a retrospective analysis of the situation and process of treating skiers' injuries in the medical station of the Wanlong ski resort in Chongli and the nearest treatment hospital, and to provide a basis for the establishment and optimization of the treatment process between the medical station of the Winter Olympics ski resort and the nearest treatment hospital, and to gain experience for medical security of mass skiing.
METHODS:
The data of all ski injuries in Chongli District were collected from the medical station of the Wanlong ski resort during the 2018-2019 snow season (November 2018 to April 2019) and the nearest treatment hospital during two periods (March 2019, and November 2019 to January 2020). The differences of injury causes, injury types, injury sites, and treatment effects of the injured skiers were analyzed.
RESULTS:
A total of 755 cases of ski injuries were recorded in the medical station of Wanlong ski resort, the estimated incidence of injury was 2.02‰ per day. The nearest treatment hospital treated a total of 838 injured skiers from different ski resorts in Chongli District in the two periods. In the records of the ski resort medical station, the main causes of injury were technical defects and turnovers (53.6%). Knee joint injury rate was the highest (18.7%), followed by head and neck (12.9%) and lower limb (11.9%). The number of injuries on intermediate roads was the highest (40.0%), the greatest number of injuries (81.2%) occurred when the age of skiing was less than 5 years. In the records of the nearest treatment hospital, the injury types were fracture or fissure fracture, contusion and trauma, and muscle and soft tissue injury, accounting for 30.5%, 27.4%, and 21.2% respectively. 9.6% of the injured took the snow field ambulance to the hospital, and 50% of them suffered from fractures or fissure fractures.
CONCLUSION
The injury rate of skiing in the 2018-2019 snow season of the Wanlong ski resort in Chongli was higher than that reported by foreign literature. Severe trauma (including severe fractures and concussions) could occur and patients needed to be transferred to the nearest hospital for treatment. The ski resort medical station and the nearest treatment hospital should be strengthened with adequate medical staff and equipment, and promote cooperation in the timely referral of seriously injured patients, the organization and construction of ski patrols and the medical security of large-scale competitions, thus playing an important role in forming a grassroots network of medical security and treatment system for skiing.
Athletic Injuries/therapy*
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Child, Preschool
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Hospitals
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Humans
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Retrospective Studies
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Seasons
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Skiing

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