AIM: To provide references for the non-clinical evaluation of therapeutic targets or drugs for retinoblastoma, fluorescently labeled Y79 cells are injected into the vitreous body of BALB/c-nu mice to establish a retinoblastoma model, and the Melphalan treatment group is used as a positive control, which is verified by fluorescence imaging technology.METHODS: BALB/c-nu mice were intravitreous injected with GFP transfected Y79 cells(1.0×107 cell/mL, 3 μL)to establish the model. On the 27th day, the mice were randomly divided into model control group and different doses of Melphalan groups(1, 3, 10 μg/eye groups)according to the fluorescence value of in vivo imaging, with vitreous body single administrated and ocular symptoms observed daily. Slit-lamp examination was performed at 12, 20, 29, 35, 42, 48, 55, 76, and 83 d after modeling. In vivo imaging was performed on 12, 20, 27, 41, 48, 55, 62, 69, 76, and 83 d. At the last treatment, the eyeball, brain and cerebellum tissues were removed for histopathological examination.RESULTS: From the sixth day of modeling, cloud-like substances could be seen in the eyes of the animals, and the cloud-like substances occupied the whole eyeball of the mice in the model control group at the later stage, accompanied by irregular growth of blood vessels. After 27 days of modeling, the fluorescence value was detected in all the animals, and the fluorescence value continued to increase with the extension of modeling time. The fluorescence value of the tumor reached the peak after 69-83 days of modeling. Histological examination showed severe proliferation of intraocular tumor cells in the model control group, and tumor cells were observed in the brain of 1 model animal. In the 10 μg/eye Melphalan group, the fluorescence value was significantly decreased at 17 d after administration. The fluorescence value of the 3 μg/eye Melphalan group was significantly inhibited at 59 d after administration. No tumor cells were found in the brain tissue of animals in all Melphalan groups.CONCLUSION: After vitreous injection of Y79/pCDH-LUC-copGFP cells in BALB/c-nu mice, significant ocular lesions and proliferation of tumor cells were observed in the eyes. Meanwhile, Melphalan intervention significantly inhibited tumor cells in a dose-dependent manner, indicating that the mouse model of retinoblastoma was successfully constructed.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Objective To investigate the effect of leucine carboxyl methyltransferase 1(LCMT1)knockout on fructose-induced lipid deposition in primary mouse hepatocytes.Methods Primary hepatocytes were isolated from wild-type(WT)and hepatocyte-specific LCMT1 knockout(KO)mice via a two-step hepatic portal vein perfusion method.The cells were divided into four groups:WT-control group,WT-fructose group,KO-control group,and KO-fructose group.Cell viability was determined through Alamar-Blue assays.Hepatocyte injury was evaluated based on alanine aminotransferase and aspartate aminotransferase levels.Lipid deposition was visualized via Oil Red O staining and lipid droplet green fluorescence staining,and the cellular triglyceride content was quantified via a GPO-POD assay.The mRNA expression of lipid metabolism-related genes was detected via quantitative real-time PCR,and the protein expression of LCMT1 and PP2Ac was detected via Western blot.Results Fructose treatment did not alter cell viability significantly in any group,and no significant cell damage was observed(P＞0.05).The WT-fructose group exhibited greater accumulation of lipid droplets in hepatocytes than that in the WT-control group(P＜0.001),with significantly elevated triglyceride contents(P＜0.05).The mRNA levels of the de novo lipid synthesis genes ChREBP,SREBP-1c,and ACC1 were increased significantly(P＜0.05,P＜0.001,P＜0.001),whereas FAS expression did not differ significantly between groups(P＞0.05).The mRNA levels of the lipid uptake genes FABP1 and FATP2 also increased significantly(both P＜0.05).In contrast,the KO-fructose group presented a reduced number of lipid droplets(P＜0.01,P＜0.001),decreased triglyceride content(P＜0.05),and decreased mRNA levels of ChREBP,SREBP-1c,ACC1,FABP1,and FATP2(P＜0.01,P＜0.001,P＜0.001,P＜0.001,P＜0.05);CPT1 mRNA levels were markedly increased(P＜0.01).Total PP2Ac expression was significantly higher(P＜0.05)and PP2Ac demethylation was significantly lower(P＜0.01)in the WT-fructose group than in the WT-control group.In the KO-control group,total PP2Ac expression remained unchanged(P＞0.05),whereas PP2Ac demethylation was markedly elevated(P＜0.001).Compared with levels in the WT-fructose group,the KO-fructose group presented markedly lower total PP2Ac expression and significantly higher PP2Ac demethylation levels(P＜0.05,P＜0.01,respectively).Conclusions LCMT1 knockout alleviates fructose-induced lipid deposition in primary hepatocytes by inhibiting lipid uptake,increasing fatty acid oxidation,and downregulating de novo lipid synthesis.These effects are medicated by the LCMT1 knockout-mediated upregulation of PP2Ac demethylation,thereby modulating PP2A activity.

Constipation,a common functional gastrointestinal disorder,not only severely impairs patients'quality of life but is also highly comorbid with psychiatric conditions such as anxiety and depression.Emerging evidence indicates that gut microbiota dysbiosis is a critical link connecting these two disease states.On one hand,dysbiosis exacerbates constipation by affecting host metabolism and intestinal function;on the other,it plays a central role in the pathophysiology of mood disorders.This complex interaction is primarily mediated through the"microbiota-gut-brain axis."Therefore,elucidating the intrinsic relationship among anxiety,depression,gut microbiota,and constipation has become a frontier of interdisciplinary research.

Objective:To explore the implementation method of the "daily-monthly-quarterly" quality control model based on total quality management (TQM) theory in nursing quality management, and evaluate its application effectiveness.Methods:A quasi-experimental research method was used. The quarterly quality control model employed at Shanxi Medical University Second Hospital from 2018 to 2019 was set as the control group, and the"day-month-quarter" quality control model based on TQM implemented from 2020 to 2022 was set as the observation group. The nurse practice environment assessment scores from 2018 to 2022 were analyzed; the nursing quality-sensitive indicators between the two groups were compared, including the incidence rate of overall adverse event, falls among hospitalized patients, pressure ulcers of stage 2 and above, unplanned extubations, and catheter-related infections (central venous catheter-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections).Results:The nurse practice environment assessment scores from 2018 to 2022 were (69.11 ± 19.66), (75.20 ± 18.70), (77.60 ± 17.65), (82.45 ± 16.44), and (88.00 ± 15.06). The differences compared to the previous year were statistically significant ( t=3.63-9.24, all P<0.05).After the intervention, the incidence rates of overall adverse events, falls among hospitalized patients, unplanned extubation, central venous catheter-related bloodstream infections, and ventilator-associated pneumonia in the control group were 0.385% (499/129 678), 0.072% (94/129 678), 0.051% (66/129 678), 0.037% (23/62 390), and 0.746% (43/5 761). Compared to 0.258% (551/213 851), 0.048% (103/213 851), 0.033% (71/213 851), 0.019% (19/98 642), and 0.444% (88/19 826) in the observation group. The differences were statistically significant ( χ2values were 3.89-42.83, all P<0.05). There were no statistically significant differences in the incidence rates of pressure ulcers of stage 2 and above and catheter-associated urinary tract infections (both P>0.05). Conclusions:The "daily-monthly-quarterly" quality control model based on TQM is beneficial in improving nursing quality and ensuring patient safety.

Constipation,a common functional gastrointestinal disorder,not only severely impairs patients'quality of life but is also highly comorbid with psychiatric conditions such as anxiety and depression.Emerging evidence indicates that gut microbiota dysbiosis is a critical link connecting these two disease states.On one hand,dysbiosis exacerbates constipation by affecting host metabolism and intestinal function;on the other,it plays a central role in the pathophysiology of mood disorders.This complex interaction is primarily mediated through the"microbiota-gut-brain axis."Therefore,elucidating the intrinsic relationship among anxiety,depression,gut microbiota,and constipation has become a frontier of interdisciplinary research.

Objective To investigate the effect of leucine carboxyl methyltransferase 1(LCMT1)knockout on fructose-induced lipid deposition in primary mouse hepatocytes.Methods Primary hepatocytes were isolated from wild-type(WT)and hepatocyte-specific LCMT1 knockout(KO)mice via a two-step hepatic portal vein perfusion method.The cells were divided into four groups:WT-control group,WT-fructose group,KO-control group,and KO-fructose group.Cell viability was determined through Alamar-Blue assays.Hepatocyte injury was evaluated based on alanine aminotransferase and aspartate aminotransferase levels.Lipid deposition was visualized via Oil Red O staining and lipid droplet green fluorescence staining,and the cellular triglyceride content was quantified via a GPO-POD assay.The mRNA expression of lipid metabolism-related genes was detected via quantitative real-time PCR,and the protein expression of LCMT1 and PP2Ac was detected via Western blot.Results Fructose treatment did not alter cell viability significantly in any group,and no significant cell damage was observed(P＞0.05).The WT-fructose group exhibited greater accumulation of lipid droplets in hepatocytes than that in the WT-control group(P＜0.001),with significantly elevated triglyceride contents(P＜0.05).The mRNA levels of the de novo lipid synthesis genes ChREBP,SREBP-1c,and ACC1 were increased significantly(P＜0.05,P＜0.001,P＜0.001),whereas FAS expression did not differ significantly between groups(P＞0.05).The mRNA levels of the lipid uptake genes FABP1 and FATP2 also increased significantly(both P＜0.05).In contrast,the KO-fructose group presented a reduced number of lipid droplets(P＜0.01,P＜0.001),decreased triglyceride content(P＜0.05),and decreased mRNA levels of ChREBP,SREBP-1c,ACC1,FABP1,and FATP2(P＜0.01,P＜0.001,P＜0.001,P＜0.001,P＜0.05);CPT1 mRNA levels were markedly increased(P＜0.01).Total PP2Ac expression was significantly higher(P＜0.05)and PP2Ac demethylation was significantly lower(P＜0.01)in the WT-fructose group than in the WT-control group.In the KO-control group,total PP2Ac expression remained unchanged(P＞0.05),whereas PP2Ac demethylation was markedly elevated(P＜0.001).Compared with levels in the WT-fructose group,the KO-fructose group presented markedly lower total PP2Ac expression and significantly higher PP2Ac demethylation levels(P＜0.05,P＜0.01,respectively).Conclusions LCMT1 knockout alleviates fructose-induced lipid deposition in primary hepatocytes by inhibiting lipid uptake,increasing fatty acid oxidation,and downregulating de novo lipid synthesis.These effects are medicated by the LCMT1 knockout-mediated upregulation of PP2Ac demethylation,thereby modulating PP2A activity.

Objective:To explore the implementation method of the "daily-monthly-quarterly" quality control model based on total quality management (TQM) theory in nursing quality management, and evaluate its application effectiveness.Methods:A quasi-experimental research method was used. The quarterly quality control model employed at Shanxi Medical University Second Hospital from 2018 to 2019 was set as the control group, and the"day-month-quarter" quality control model based on TQM implemented from 2020 to 2022 was set as the observation group. The nurse practice environment assessment scores from 2018 to 2022 were analyzed; the nursing quality-sensitive indicators between the two groups were compared, including the incidence rate of overall adverse event, falls among hospitalized patients, pressure ulcers of stage 2 and above, unplanned extubations, and catheter-related infections (central venous catheter-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections).Results:The nurse practice environment assessment scores from 2018 to 2022 were (69.11 ± 19.66), (75.20 ± 18.70), (77.60 ± 17.65), (82.45 ± 16.44), and (88.00 ± 15.06). The differences compared to the previous year were statistically significant ( t=3.63-9.24, all P<0.05).After the intervention, the incidence rates of overall adverse events, falls among hospitalized patients, unplanned extubation, central venous catheter-related bloodstream infections, and ventilator-associated pneumonia in the control group were 0.385% (499/129 678), 0.072% (94/129 678), 0.051% (66/129 678), 0.037% (23/62 390), and 0.746% (43/5 761). Compared to 0.258% (551/213 851), 0.048% (103/213 851), 0.033% (71/213 851), 0.019% (19/98 642), and 0.444% (88/19 826) in the observation group. The differences were statistically significant ( χ2values were 3.89-42.83, all P<0.05). There were no statistically significant differences in the incidence rates of pressure ulcers of stage 2 and above and catheter-associated urinary tract infections (both P>0.05). Conclusions:The "daily-monthly-quarterly" quality control model based on TQM is beneficial in improving nursing quality and ensuring patient safety.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy ; Taurine ; Macrophages/metabolism* ; Protein Kinases/metabolism* ; RNA, Messenger