Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

Objective:To analyze the disease burden of kidney cancer, bladder cancer and prostate cancer and attributed risk factors in China from 1990 to 2019, and provide reference for the development of comprehensive prevention and control strategies.Methods:Based on the Global Burden of Disease Study 2019 platform, we collected the crude and age-standardized incidence rate, age-standardized mortality rate (ASMR), and disability-adjusted life year (DALY) of kidney cancer, bladder cancer and prostate cancer in China from 1990 to 2019. By using the log-linear regression model, trends were analyzed for overall and risk-attributable disease burden by calculating the average annual percentage change (AAPC).Results:From 1990 to 2019, the crude incidence rates of kidney cancer, bladder cancer and prostate cancer showed increasing trends in China, with an AAPC of 5.4% (95% CI: 4.9% - 5.9%), 4.1% (95% CI: 3.9% - 4.2%) and 5.6% (95% CI: 5.3% - 6.0%) (all P<0.001), respectively. Similar trends were found in age-standardized incidence rates with smaller AAPCs. For kidney cancer, the ASMR and age-standardized DALY rate significantly increased, with AAPC of 2.2% (95% CI: 1.5%-2.8%) and 1.5% (95% CI: 1.2%-1.9%) (all P<0.001), while the ASMR of bladder cancer and prostate cancer decreased gradually, with AAPC of -0.6% (95% CI: -0.7% - -0.5%) ( P<0.001) and -0.2% (95% CI: -0.3% - -0.1%) ( P=0.002). The age-standardized DALY rate of bladder cancer and prostate cancer decreased gradually, with AAPC of -0.6% (95% CI: -0.8% - -0.4%) ( P<0.001) and -0.2% (95% CI: -0.3% - -0.1%) ( P=0.002). Smoking was responsible for 48.2% of bladder cancer, 18.8% of kidney cancer and 9.8% of prostate cancer in total DALY. The age-standardized DALY rate of kidney cancer caused by smoking and high BMI showed an increasing trend, with AAPC of 3.0% (95% CI: 2.8%-3.2%) and 4.9% (95% CI: 4.7%-5.0%) (all P<0.001), and smoking-attributed age-standardized DALY rates of bladder cancer and prostate cancer decreased gradually with AAPC of -0.4% (95% CI: -0.6% - -0.2%) ( P<0.001) and -0.3% (95% CI: -0.4% - -0.1%) ( P=0.001). Conclusions:In the past 30 years, the disease burden of kidney cancer, bladder cancer and prostate cancer in China increased gradually, while the deaths and DALY of bladder cancer and prostate cancer decreased slightly. We should continue to strengthen the primary prevention strategies for smoking, obesity and other risk factors, and explore the appropriate screening tests and population-based screening strategies.

OBJECTIVE: To investigate the role and underlying mechanism of human myeloid differentiation protein 2 (MD2) in the process of neuronal death induced by lipopolysaccharide (LPS) by establishing an in vitro model of sepsis-associated encephalopathy (SAE) by LPS. METHODS: Healthy C57BL/6J mice at 14-18 days of gestation were selected, and brain cortical tissue was taken from fetal mice. Neurons were stimulated with 0 (control), 1, 5 and 10 g/L of LPS for 24 hours. The release of lactate dehydrogenase (LDH) was detected and the death of neurons was observed. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukins (IL-6, IL-1β), in order to determine the optimal dose of LPS for establishing an in vitro neuroinflammation model of SAE. The cells were divided into blank control group and LPS group. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) was used to discover apoptosis. Western blotting was used to detect the expression of the relevant protein markers activated caspase-3, necroptosis-associated protein neuronal receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and phosphorylated RIPK3 (p-RIPK3). Immunofluorescence chemical staining was used to detect the expressions of p-RIPK3 and microtubule-associated protein 2 (MAP2) to evaluate the type of cell death and the degree of neuronal death. Western blotting was used to detect MD2 expression. Immunofluorescence chemical staining was performed to observe the expression and distribution of p-RIPK3 and MD2 in neurons to assess whether MD2 was involved in the inflammatory response promoting neuronal death. In addition, the cells were divided into blank control group, LPS group, and MD2 interfering peptide group (LPS+TC group), and the levels of IL-6, IL-1β and LDH were detected to evaluate whether interfering with MD2 can alleviate LPS induced neuroinflammation. RESULTS: 10 g/L LPS induced notable neuronal death, and the release of LDH in neurons stimulated with this concentration for 24 hours was significantly higher than that in the blank control group (relative release: 1.45±0.04 vs. 1.00±0.00, P < 0.01), indicating apoptosis and necroptosis occurred in neurons, and the levels of inflammatory factors IL-6 and IL-1β were remarkable increased [IL-6 (relative level): 1.94±0.04 vs. 1.00±0.00, IL-1β (relative level): 1.53±0.09 vs. 1.00±0.00, both P < 0.01]. Compared with the blank control group, the apoptosis of cells, cleaved-caspase-3 expression, the p-RIPK3/RIPK3 ratio, and p-RIPK3 expression around neurons in the LPS group were significantly increased [cleaved-caspase-3/GAPDH: 1.55±0.10 vs. 1.00±0.00, P < 0.01; p-RIPK3/RIPK3 ratio (relative value): 1.54±0.06 vs. 1.00±0.00, P < 0.05], which suggested that typical apoptosis and necroptosis apoptosis occurred in neurons in the septic environment. Furthermore, MD2 expression was significantly increased in the LPS group compared with the blank control group (MD2/GAPDH: 1.91±0.07 vs. 1.00±0.00, P < 0.01), and MD2 expression around neurons was increased, indicating that LPS-induced MD2 upregulation may play a key role in neuroinflammation and induction of neuronal death in sepsis. In addition, compared with the LPS group, the MD2-interfering peptide could reduce the expression levels of inflammatory factors IL-6 and IL-1β [IL-6 (relative level): 1.16±0.08 vs. 1.94±0.04, IL-1β (relative level): 1.15±0.05 vs. 1.75±0.09, both P < 0.01] and decrease LDH release (relative release: 1.09±0.01 vs. 1.44±0.04, P < 0.05). CONCLUSIONS LPS induced neuronal inflammatory responses via MD2, which ultimately leads to apoptosis and necroptosis. Interfering with MD2 reduces inflammation and inhibits neuronal death.
Mice ; Humans ; Animals ; Sepsis-Associated Encephalopathy ; Caspase 3 ; Interleukin-6 ; Neuroinflammatory Diseases ; Lipopolysaccharides ; Mice, Inbred C57BL ; Cell Differentiation ; Tumor Necrosis Factor-alpha

Objective:To investigate the value of radiomics based on unenhanced CT texture analysis in predicting the WHO/International Society of Urological Pathology (ISUP) grading of clear cell renal cell carcinoma (ccRCC).Methods:Postoperative pathology-confirmed ccRCC subjects ( n=90) who received CT scanning and had a definite pathological grading in Cancer Hospital of the University of Chinese Academy of Sciences were collected retrospectively from December 2016 to May 2019. The cases were randomly divided into training group ( n=63) and test group ( n=27) as a ratio of 7∶3. All cases were classified into low grade (grades Ⅰ and Ⅱ, n=57) and high grade (grades Ⅲ and Ⅳ, n=37) according to the new pathological grading (WHO/ISUP grading, version 2016) of renal carcinoma. 3D-ROI segmentation was performed on unenhanced CT images and 93 texture features were extracted. The least absolute shrinkage and selection operator (LASSO) regression was used to reduct dimension of texture parameters and then the radiomics score (Rad-score) was established. The logistic regression was used to develop the prediction model with the pathological grading as the gold standard. The ROC curve and calibration curve were used to evaluate the predictive performance of the model, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. The Hosmer-Lemeshow test was used to evaluate calibration degree of the model. Results:The 10 non-zero coefficient texture features were screened out through dimension reduction steps. The Rad-score was formed according to the linear combination of these ten features and corresponding coefficients, and then the prediction model was developed. The AUC of the model in training group was 0.933 (95%CI 0.862-1.000), the sensitivity was 92.3%, the specificity was 89.2%, and the model accuracy was 90.5%. The calibration curve showed the good calibration ( P=0.257). The AUC value in test group was 0.875 (95%CI 0.734-1.000), the sensitivity, specificity and accuracy were 72.7%, 87.5% and 81.5%. The calibration curve showed the good calibration ( P=0.125). Conclusion:The radiomics prediction model based on unenhanced CT texture analysis have application potential for the evaluation of WHO/ISUP grading of ccRCC.

Objective:To investigate the correlation between venous collateral circulation and clinical data such as symptoms, parenchymal injury, and prognosis in patients with cerebral venous thrombosis(CVT).Methods:The clinical and imaging data of patients with CVT diagnosed in the department of Neurosurgery of the Third Affiliated Hospital of Southern Medical University from December 2011 to August 2018 were retrospectively analyzed. A total of 32 patients with CVT were included, 19 males and 13 females, aged from 20 to 60 (39±12) years. All patients underwent cerebral angiography, individualized delayed rotational phlebography. According to the number and diameter of collateral circulation and the phenomenon of flow delay of contrast medium, the collateral venous circulation scale (CVCS) was developed and divided into 3 levels. The clinical data (risk factors, course of disease, clinical symptoms), imaging data (parenchymal injury, thrombus site), treatment (endovascular treatment, decompressive craniectomy) and prognosis of all patients were recorded. The differences in clinical data, imaging appearances, parenchymal injury, and prognosis between patients with different CVCS were compared, and the correlation between variables with statistically significant differences and CVCS was compared using the Gamma method or Spearman correlation analysis.Results:Among the 32 patients with CVT, 9 were CVCS 0, 13 were CVCS 1 and 10 were CVCS 2. Among them, there were 19 cases of neurological deficit and 17 cases of brain parenchymal injury. There were significant differences in course of disease, neurological deficit, focal dyskinesia, language dysfunction, consciousness disorder, isolated headache, deep vein thrombosis, cortical vein thrombosis and prognosis across different CVCS ( P<0.05). Correlation analysis showed that CVCS was positively correlated with course of disease and isolated headache ( r=0.724, 0.637, P<0.001), and negatively correlated with neurological deficit symptoms, focal dyskinesia, disturbance of consciousness, brain parenchymal injury and deep vein thrombosis ( r=-0.797, -0.451, -0.782, -0.697, -0.427, P<0.05). The results of 90 days follow-up showed that there were 18 cases with mRS 0, 6 cases with mRS 1, 2 cases with mRS 2-4, and 1 case with mRS 5-6 points. There was a negative correlation between CVCs grading and mRS score at 90 days ( r=-0.732, P<0.001). Conclusion:Lower cerebral venous collateral circulation grade is associated with higher incidence of brain parenchymal injury, neurological deficit symptoms, and worse clinical prognosis.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

We have previously reported that Cystatin C (CysC) is a pivotal mediator in the neuroprotection induced by hyperbaric oxygen (HBO) preconditioning; however, the underlying mechanism and how CysC changes after stroke are not clear. In the present study, we demonstrated that CysC expression was elevated as early as 3 h after reperfusion, and this was further enhanced by HBO preconditioning. Concurrently, LC3-II and Beclin-1, two positive-markers for autophagy induction, exhibited increases similar to CysC, while knockdown of CysC blocked these elevations. As a marker of autophagy inhibition, p62 was downregulated by HBO preconditioning and this was blocked by CysC knockdown. Besides, the beneficial effects of preserving lysosomal membrane integrity and enhancing autolysosome formation induced by HBO preconditioning were abolished in CysC rats. Furthermore, we demonstrated that exogenous CysC reduced the neurological deficits and infarct volume after brain ischemic injury, while 3-methyladenine partially reversed this neuroprotection. In the present study, we showed that CysC is biochemically and morphologically essential for promoting autophagic flux, and highlighted the translational potential of HBO preconditioning and CysC for stroke treatment.
Animals ; Autophagy ; physiology ; Beclin-1 ; metabolism ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; pathology ; therapy ; Cystatin C ; genetics ; metabolism ; Disease Models, Animal ; Gene Expression ; Gene Knockdown Techniques ; Hyperbaric Oxygenation ; Lysosomes ; metabolism ; pathology ; Male ; Microtubule-Associated Proteins ; metabolism ; Neurons ; metabolism ; pathology ; Neuroprotection ; physiology ; Oxygen ; therapeutic use ; Random Allocation ; Rats, Sprague-Dawley ; Rats, Transgenic ; Reperfusion Injury ; metabolism ; pathology ; therapy

OBJECTIVE: To explore the high risk factors of adult complex appendicitis, and to provide a reference for the development of a reasonable treatment strategy for acute appendicitis. METHODS: A retrospective case-control study was conducted to collect clinical data of 312 adult patients with acute appendicitis confirmed by pathology undergoing appendectomy, including open and laparoscopic surgery, from May 2011 to August 2016 at Affiliated Hospital of Qingdao University. Age <14 years old, pregnant women, complicating abscess around the appendix, AIDS, blood system diseases, autoimmune diseases, inflammatory bowel disease or progressive cancer patients were excluded. According to the intra-operative findings and pathological types, patients were divided into complex appendicitis(112 cases, including gangrene and perforation) and non-complex appendicitis (200 cases, including simple and non-perforated appendicitis, ie suppurative appendicitis). After comparing the clinical data of these two groups, statistically significant variables were induded for multivariate logistic regression analysis to identify risk factors of complex appendicitis, and to establish a regression model. Enter method was applied to establish the regression equation: P=ExpiΣBiXi/1+ExpΣBiXi, and to calculate the relative risk of each variable. Meanwhile, retrospective and prospective verification was performed on this predictive model (cases of acute appendicitis from September 2016 to December 2017 were further collected). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of complex appendicitis were calculated with the regression model. RESULTS: Comparison of the clinical data between the complex appendicitis group and the non-complex appendicitis group showed that differences of 10 preoperative indexes were statistically significant, including period from abdominal pain to admission [(59.1±42.6) hours vs. (47.5±34.4) hours, t=3.051, P=0.002], white blood cell count [(12.9±3.7)×10/L vs. (9.2±4.0)×10/L, t=9.755, P<0.001], neutrophil count [(9.8±4.0)× 10/L vs.(7.1±3.9)×10/L, t=6.020, P<0.001], neutrophil percentage[(84.5±8.7)% vs.(68.2±16.0)%, t=12.754, P<0.001], C-reactive protein levels [(86.0±45.4) μg/L vs. (55.9±35.8) μg/L, t=7.614, P<0.001], serum albumin levels [(334.0±4.8) g/L vs. ( 41.0±4.3) g/L, t=16.055, P<0.001], vomiting ratio [44.6%(50/112) vs. 23.5%(47/200), χ²=14.980, P<0.001], high fever(≥39°C) ratio [16.1%(18/112) vs. 7.5%(15/200), χ²=5.577, P=0.022], the proportion of patients ≥60 years old [22.3%(25/112) vs. 13.0%(26/200), χ²=4.562, P=0.038] and previous history of appendicitis [16.1%(18/112) vs. 7.5%(15/200), χ²=5.577, P=0.022]. The above 10 variables were included in the logistic regression model for multivariate analysis. The results showed that six variables were associated with complex appendicitis. According to their strength, they were old age (≥60 years old) X1(OR=5.094), high fever (≥39°C) X2(OR=4.464), neutrophil count X6 (OR=1.269), neutrophil percentage X4 (OR=1.077), C-reactive protein level X5 (OR=1.027), and serum albumin level X3 (OR=0.763). A predictive regression model was established: P=1/[1+e], whose sensitivity and specificity of judging complex appendicitis were 76.8%(86/112) and 90.0%(180/200),respectively. Sensitivity and specificity for predictive value of complex appendicitis in further prospective validation of the model were 76.2%(48/63) and 81.1% (30/37), respectively. CONCLUSIONS Age ≥ 60 years old, body temperature ≥39°C, increased neutrophil count, neutrophil percentage and C-reactive protein levels, and hypoalbuminemia are risk factors for complex appendicitis. The establishment of predictive model may help determine complex appendicitis.
Acute Disease ; Adolescent ; Adult ; Age Factors ; Appendicitis ; diagnosis ; epidemiology ; pathology ; Case-Control Studies ; Female ; Humans ; Leukocyte Count ; Middle Aged ; Models, Statistical ; Pregnancy ; Retrospective Studies ; Risk Factors

AIM: To investigate the effects of propofol on the expression of tissue-type plasminogen activator (tPA) and matrix metalloproteinase 9 (MMP9) in the hippocampus and the cognitive function in neonatal rats.METHODS: The 7-day-old rats were randomly divided into 3 groups: the rats in control (CON) group were intraperitoneally injected with normal saline for 7 d;the rats in single dose of propofol anesthesia (SP) group were intraperitoneally injected with normal saline for 6 d and with propofol on the 7th day;the rats in repeated dose of propofol anesthesia (RP) group were intraperitoneally injected with propofol for 7 d.Blood glucose and blood gas analysis were tested in 6 rats of each group.The rats were randomly selected from each group to isolate the hippocampal tissues at 2 h, 24 h, 48 h, 72 h and 30 d after the last injection.The spatial learning and memory functions of the other rats aged 25 d were determined by Morris water maze.The morphological changes of the hippocampus were observed by HE staining and Nissl's staining.The expression of tPA and MMP9 at mRNA and protein levels was determined by RT-PCR and Western blot.RESULTS: Compared with group CON, the protein expression of tPA and MMP9 in RP group was significantly decreased at each time point, while no significant decrease was observed in SP group except at the time point of 24 h.Compared with CON group, the mRNA expression of tPA and MMP9 was down-regulated obviously in RP group, which was not significantly down-regulated in SP group.From the 3rd training day of Morris water maze beginning, the escape latency was prolonged, and the space exploration time and the number of crossing the original platform location were reduced in RP group compared with CON group and SP group, while no significant difference was observed between CON group and SP group.Compared with CON group, the number of nerve cells reduced and nerve cells arranged in disorder in the hippocampus in RP group.Moreover, the number of Nissl body decreased significantly and finally developed into neuronal degeneration and necrosis in RP group, and no significant difference between SP group and CON group was observed.CONCLUSION: Repeated dose of propofol anesthesia leads to long-term cognitive dysfunction in neonatal rats, which may be related to the down-regulation of tPA and MMP9 expression and destruction of normal morphology and function of neurons in hippocampus, whereas single dose of propofol anesthesia has no such effects.