Objective To explore the effects of proteasome 20S subunit beta 8 (PSMB8) on the proliferation,migration,and invasion of clear cell renal cell carcinoma (ccRCC) cells and whether PSMB8 promotes tumor progression by activating the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. Methods The Cancer Genome Atlas was employed to analyze the mRNA levels of PSMB8 in ccRCC and normal tissue,and the expression levels of PSMB8 in ccRCC tissue and cells were determined by real-time quantitative PCR,Western blotting,and immunohistochemistry.Furthermore,the cell lines with stable overexpression and knockdown of PSMB8 were constructed.The CCK-8 assay and colony formation assay were employed to examine the cell proliferation,and the wound healing assay and Transwell assay were employed to examine the invasion and migration of cells.Kyoto Encyclopedia of Genes and Genomes pathway enrichment was performed to analyze the co-expressed genes of PSMB8.Western blotting was used to measure the phosphorylation levels of the proteins in the MEK/ERK signaling pathway.Finally,the rescue experiment was carried out with the ERK agonist C16-PAF. Results Compared with the normal tissue,the ccRCC tissue showed up-regulated mRNA and protein levels of PSMB8 (both P<0.001),which were associated with the TNM stage of patients with ccRCC (P<0.001).Compared with the negative control group,overexpression of PSMB8 promoted the proliferation (P=0.021,P=0.039),migration and invasion (all P<0.001) of 786-O and ACHN cells,and the knockdown of PSMB8 inhibited the proliferation (P=0.022,P=0.005),migration and invasion (all P<0.001) of 786-O and ACHN cells.The pathway enrichment analysis of co-expressed genes of PSMB8 predicted the mitogen-activated protein kinase signaling pathway (P<0.001).After the knockdown of PSMB8,786-O and ACHN cells showed lowered phosphorylation levels of MEK1/2 (P=0.017,P=0.016) and ERK1/2 (P=0.010,P=0.040) and down-regulated transcription levels of ERK downstream factors c-Myc (P=0.043,P=0.038),c-Fos (P=0.025,P=0.008),and CyclinD1 (P=0.006,P=0.047).Compared with the ERK agonist C16-PAF group,the PSMB8 knockdown + C16-PAF group showed inhibited proliferation (P=0.003,P=0.002),migration and invasion (all P<0.001) of 786-O and ACHN cells. Conclusion PSMB8 may promote the proliferation,migration,and invasion of ccRCC cells by activating the MEK/ERK signaling pathway.
Objective To explore the effect and mechanism of uric acid (UA) in regulating the larval growth and development of Drosophila melanogaster. Methods A total of 1350 newly hatched first-instar larvae of wild-type Drosophila melanogaster (W1118) were collected,and the Drosophila melanogaster model of hyperuricemia was constructed with a high purine diet.The larvae were assigned into three groups (n=150):control (standard corn meal medium),low-dose adenine (corn meal medium containing 0.05% adenine),and high-dose adenine (corn meal medium containing 0.10% adenine),and two parallel groups were set up.The growth and development of larvae in each group was observed,and the UA and hormone levels were measured.In addition,the expression levels of genes involved in growth and development were determined. Results Compared with the control group,the low- and high-dose adenine groups showed elevated UA levels (both P<0.001) and prolonged developmental period (P=0.024,P<0.001).The high-dose adenine group showed decreased survival rate,pupation rate,and eclosion rate and elevated levels of juvenile hormone (JH) and 20-hydroxyecdysone (20E) (all P<0.001).The PCR results showed that compared with the control group,high-dose adenine upregulated the mRNA levels of reactive oxygen species (ROS),forkhead box O (FOXO),and mammalian target of rapamycin (mTOR) while downregulating the mRNA levels of Sestrin,mTOR complex 1(mTORC1),and AMP-activated protein kinase (all P<0.001). Conclusion High concentrations of UA may promote the expression of ROS/FOXO/mTORC1/mTOR signaling pathway by regulating the levels of JH and 20E,thereby inhibiting the larval growth and development of Drosophila melanogaster.
Objective To explore the mechanism of butylphthalide (NBP) in regulating microglia activation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy after carbon monoxide poisoning (DEACMP). Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized into three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegetable oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-binding adapter molecule 1 (IBA1) was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA. Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency (P=0.001,P=0.029),reduced nerve cells (P=0.001,P=0.035),up-regulated expression of IBA1 (P=0.001,P=0.042),increased mean fluorescence intensity of IBA1 (P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α (TNF-α) (P=0.002,P=0.024),interleukin (IL)-6 (P=0.001,P=0.015),and IL-1β (P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency (P=0.025),increased nerve cells (P=0.039),down-regulated expression of IBA1 (P=0.035),decreased average fluorescence intensity of IBA1 (P=0.031),and lowered levels of TNF-α (P=0.028),IL-6 (P=0.037),and IL-1β (P=0.034). Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cognitive dysfunction and brain tissue damage caused by DEACMP.
Objective To develop the knowledge,attitude,and practice evaluation scale for teachers’ early childhood sex education and analyze the reliability and validity of the scale,providing evaluation tools for the research on teachers’ early childhood sex education. Methods On the basis of relevant guidelines,publications,and the theory of knowledge,attitude,and practice,a preliminary pool of items for the scale was formed by group discussions.The scale was drafted after two rounds of Delphi expert consultation.In May 2023,stratified cluster sampling was conducted,and 535 preschool teachers from Changshou District,Chongqing were selected for a survey.Cronbach’s α coefficient,split-half reliability,exploratory factor analysis,and content validity were adopted to assess the reliability and validity of the scale. Results An evaluation scale for teachers’ early childhood sex education was formulated,involving 27 items in 3 dimensions of knowledge,attitude,and practice.The total Cronbach’s α coefficient of the scale was 0.875,and that of the knowledge,attitude,and practice dimensions were 0.902,0.743,and 0.879,respectively.The total split-half reliability of the scale was 0.937,and that of the knowledge,attitude,and practice dimensions were 0.934,0.821,and 0.912,respectively.The content validity of the scale was good,with a factor loading range of 0.500-0.836 and a cumulative variance contribution rate of 61.57.The average score of teachers’ knowledge,attitude,and practice in sex education was 72.85±7.13,with a good rate of 70.84%. Conclusions The developed scale for evaluating teacher’s early childhood sex education demonstrates good reliability and validity,and it can be used to evaluate the teachers’ knowledge,attitude,and practice in early childhood sex education.The evaluation results indicate that teachers have low levels of knowledge,attitude,and practice in sex education,and relevant departments need to carry out training on the sex education for young children.
Objective To analyze the risk factors of septic cardiomyopathy (SC),and to construct and evaluate the risk prediction model of SC. Methods The clinical data of patients with sepsis were extracted from MIMIC-Ⅳ database and randomized into a training set and a validation set at a ratio of 7 to 3.According to the presence or absence of SC,the patients were assigned into SC and non-SC groups.The independent risk factors of SC were determined by univariate and multivariate Logistic regression analysis,and a risk prediction model and a nomogram were established.The area under the receiver operating characteristic curve (AUC),calibration curve,and decision curve analysis (DCA) were employed to evaluate the distinguishing degree,calibration,and clinical applicability of the model,respectively. Results A total of 2628 sepsis patients were enrolled in this study,including 1865 patients in the training set and 763 patients in the validation set.There was no significant difference in the incidence of SC between the training set and the validation set (58.98% vs. 62.25%,P=0.120).Except chronic obstructive pulmonary disease (P=0.015) and length of stay in intensive care unit (P=0.016),there was no significant difference in other clinical indicators between the two groups (all P>0.05).Logistic regression analysis showed that coronary heart disease (P=0.028),heart failure (P<0.001),increased neutrophil count (P=0.001),decreased lymphocyte count (P=0.036),increased creatine kinase isoenzyme (P<0.001),and increased blood urea nitrogen (P=0.042) were independent risk factors for SC.The AUC of the nomogram prediction model in the training set and validation set was 0.759 (95% CI=0.732-0.785) and 0.765 (95% CI=0.723-0.807),respectively.The established model showcased good fitting degrees in both data sets (training set:P=0.075;validation set:P=0.067).The DCA results showed that the nomogram prediction model had good clinical applicability. Conclusion The nomogram prediction model based on basic diseases and clinical biochemical indicators can effectively predict the risk of SC occurrence.
Objective To explore the risk factors for the returning of pediatric liver transplant recipients to the intensive care unit (ICU) and provide reference for the clinical decision-making after surgery. Methods A retrospective analysis was conducted with the information of all the pediatric patients who underwent liver transplantation in Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine and were returned to the ICU from 2019 to 2021.The patients returned to the ICU during hospitalization and the reasons for the return were recorded.Each patient of ICU return was matched with three pediatric patients who did not return to the ICU during hospitalization.The basic information,the vital signs and laboratory indicators on the day of transfer from ICU,immunosuppressants and drug concentrations were compared between the two groups.Multivariate Logistic regression analysis was performed to explore the risk factors for the returning of pediatric liver transplant recipients to the ICU. Results The returning rate of pediatric liver transplant recipients to the ICU was 4.36%,and it was 16.00% within 48 h.The main reasons for the return included respiratory complications,abdominal infections,and hepatic vascular occlusion.Multivariate Logistic regression analysis showed that post-operative red blood cell transfusion (OR=4.554,95%CI=1.743-11.901,P=0.002) and high serum level of uric acid (OR=1.005,95%CI=1.001-1.009,P=0.014) were the risk factors for returning to the ICU.High diastolic blood pressure (OR=0.922,95%CI=0.885-0.960,P<0.001) and high total protein level (OR=0.937,95%CI=0.891-0.986,P=0.012) were the protective factors for returning to the ICU. Conclusion Post-operative red blood cell transfusion and high serum level of uric acid are independent risk factors for the returning of pediatric liver transplant recipients to the ICU.
Objective To explore the research hotspots on systemic lupus erythematosus (SLE) in pregnancy based on the bibliometric analysis of the related articles published from 2018 to 2023 and provide directions for the future research in this field. Methods PubMed,Web of Science,and Embase were searched for the articles on SLE in pregnancy that were published from January 1,2018 to December 31,2023.VOSviewer was used to visualize the high-frequency keywords in the selected articles. Results A total of 266 articles were selected,from which 25 high-frequency keywords were extracted.The bibliometric analysis showed that the available studies about SLE in pregnancy mainly focused on maternal complications,maternal and fetal outcomes,and medications.The studies were limited regarding the predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring. Conclusion Maternal complications,maternal and fetal outcomes,and medications are currently hotspots in the research on SLE in pregnancy,while predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring may become future research directions.
Objective To construct a continuous nursing quality evaluation indicator system for inflammatory bowel disease patients and provide a basis for the evaluation of continuous nursing quality. Methods On the basis of Donabedian’s three-dimensional (structure,process,and outcome) quality structure,we employed literature review,qualitative interview,Delphi method,and hierarchical analysis to determine the content and weights of indicators of continuous nursing quality for the patients with inflammatory bowel disease. Results A total of 15 experts completed 2 rounds of consultation,which had the questionnaire recovery rates of 100%,the expert authority coefficients of 0.930 and 0.919,and the Kendall harmony coefficients of 0.149 and 0.177 (both P<0.001),respectively.The established nursing quality evaluation indicator system included 3 first-level indicators,10 second-level indicators,and 39 third-level indicators. Conclusion The continuous nursing quality evaluation indicator system for the patients with inflammatory bowel disease that was constructed in this study was reasonable,reliable,and practical,providing reference for evaluating the continuous nursing quality for the patients with inflammatory bowel disease.