Objective·To investigate the effects of rutin on proliferation,apoptosis,migration and invasion of osteosarcoma cells and its possible molecular mechanisms.Methods·Human osteosarcoma MG63 and U2OS cells were treated with rutin at concentrations of 10,20 and 40 μmol/L,respectively.The effects of rutin on proliferation,apoptosis,migration,and invasion of MG63 and U2OS cells were assessed by using CCK-8 assay,colony formation assay,flow cytometry,scratch closure assay,and Transwell assay.The expression levels of cell proliferation antigen Ki67,B-cell lymphoma-2(Bcl-2),and Bcl-2 associated X protein(Bax)proteins were detected by Western blotting.Twelve BALB/c nude mice were subcutaneously injected with osteosarcoma MG63 cells to establish a subcutaneous transplant tumor model.The mice were randomly divided into two groups:a control group and a rutin 40 mg/kg group(6 mice in each group).The rutin 40 mg/kg group was intraperitoneally injected with rutin(40 mg/kg),and the control group was intraperitoneally injected with an equal volume of saline,once every other day for 4 weeks.The tumor volume was measured every week.After 4 weeks,the mice were euthanized,and the tumors were excised and weighed.Immunohistochemistry was used to detect the expression of Ki67 and vascular endothelial growth factor(VEGF)in tumor tissues.TUNEL was used to detect tumor cell apoptosis.Results·Compared with MG63 and U2OS cells not treated with rutin,MG63 and U2OS cells treated with rutin at 20 and 40 μmol/L showed a significant decrease in proliferation rate,an increase in apoptotic rate,a decrease in migration and invasion abilities,a significant downregulation of Ki67 protein,and a significant increase in Bax/Bcl-2 ratio,with statistically significant differences(all P＜0.05).In addition,rutin significantly inhibited the in vivo growth of osteosarcoma cells,reduced the expression of Ki67 and VEGF in tumor tissues,and promoted cell apoptosis(all P＜0.05).Conclusion·Rutin can inhibit the proliferation,migration,and invasion of osteosarcoma cells,and promote apoptosis.

Objective·To investigate the effects of rutin on proliferation,apoptosis,migration and invasion of osteosarcoma cells and its possible molecular mechanisms.Methods·Human osteosarcoma MG63 and U2OS cells were treated with rutin at concentrations of 10,20 and 40 μmol/L,respectively.The effects of rutin on proliferation,apoptosis,migration,and invasion of MG63 and U2OS cells were assessed by using CCK-8 assay,colony formation assay,flow cytometry,scratch closure assay,and Transwell assay.The expression levels of cell proliferation antigen Ki67,B-cell lymphoma-2(Bcl-2),and Bcl-2 associated X protein(Bax)proteins were detected by Western blotting.Twelve BALB/c nude mice were subcutaneously injected with osteosarcoma MG63 cells to establish a subcutaneous transplant tumor model.The mice were randomly divided into two groups:a control group and a rutin 40 mg/kg group(6 mice in each group).The rutin 40 mg/kg group was intraperitoneally injected with rutin(40 mg/kg),and the control group was intraperitoneally injected with an equal volume of saline,once every other day for 4 weeks.The tumor volume was measured every week.After 4 weeks,the mice were euthanized,and the tumors were excised and weighed.Immunohistochemistry was used to detect the expression of Ki67 and vascular endothelial growth factor(VEGF)in tumor tissues.TUNEL was used to detect tumor cell apoptosis.Results·Compared with MG63 and U2OS cells not treated with rutin,MG63 and U2OS cells treated with rutin at 20 and 40 μmol/L showed a significant decrease in proliferation rate,an increase in apoptotic rate,a decrease in migration and invasion abilities,a significant downregulation of Ki67 protein,and a significant increase in Bax/Bcl-2 ratio,with statistically significant differences(all P＜0.05).In addition,rutin significantly inhibited the in vivo growth of osteosarcoma cells,reduced the expression of Ki67 and VEGF in tumor tissues,and promoted cell apoptosis(all P＜0.05).Conclusion·Rutin can inhibit the proliferation,migration,and invasion of osteosarcoma cells,and promote apoptosis.

Objective:To investigate the correlation between the annual professional proficiency test results and the theoretical examination score of completion assessment in standardized residency training, as well as the value of the annual professional proficiency test results in predicting whether a resident passes the theoretical examination of completion assessment.Methods:The residents who participated in the annual professional proficiency test of residency training in Affiliated Hospital 2 of Nantong University in 2019-2021 and the completion assessment of residency training in 2020-2022 were selected as subjects, and related data were collected, including sex, education background, personnel type, training specialty, the results of annual professional proficiency test, and the theoretical examination score of completion assessment. According to whether the resident passed the theoretical examination of completion assessment, they were divided into passed group and failed group. SPSS 19.0 was used to perform the chi-square test, the independent samples t-test, and the binary logistic regression analysis; the Pearson correlation coefficient was used for correlation analysis; the sensitivity analysis was represented by ROC curve. Results:Compared with the residents who passed the theoretical examination of completion assessment, the residents who did not pass the examination had a significant reduction in the proportion of the residents from our hospital and a significant increase in the proportion of the residents commissioned by foreign institutions ( χ 2=7.00, P=0.008). The passed group had a significantly higher national percentile of annual professional proficiency test score than the failed group (43.46%±26.61% vs. 23.40%±18.71%, t=6.02, P<0.001). The national percentile of annual professional proficiency test score was positively correlated with the theoretical examination score of completion assessment ( r=0.43, P<0.05). The source of residents commissioned by foreign institutions and the low percentile of annual professional proficiency test score were independent risk factors for failing the theoretical examination of completion assessment ( P=0.020 and P<0.001). The national percentile of annual professional proficiency test score had an area under the ROC curve of 0.73 (95% CI: 0.65-0.80) in predicting the outcome of theoretical examination and had a certain predictive value with a cut-off value of 15.1%. Conclusions:In addition to strengthening homogenization and professional base management for residency training, it is necessary to make full use of the results of annual professional proficiency test in standardized residency training and timely check the professional knowledge of the residents whose a national percentile of <15.1%, so as to effectively improve the pass rate of theoretical examination and the quality of training.

Objective:To analyze the epidemiological characteristics and risk factors of brucellosis in Yan'an City, and to provide a theoretical basis for scientifically formulating prevention and control measures for brucellosis.Methods:A descriptive analysis method was used to analyze the general information, epidemiological characteristics of confirmed brucellosis cases at General Hospital of Yan'an Second Medical Group from 2019 to 2023. Univariate and multivariate logistic regression models were used to analyze the risk factors for brucellosis infection in the population.Results:From 2019 to 2023, a total of 301 cases of brucellosis were confirmed, and the number of cases in each year was 1, 7, 85, 85 and 123 cases, respectively. There were 231 males and 70 females, with a gender ratio of 3.3 ∶ 1.0. The patients were mainly aged between 15 and 64 years old (88.70%, 267/301), with a higher incidence in summer and autumn (36.55%, 110/301; 30.23%, 91/301). The occupation was dominated by farmers (62.98%, 182/289). The area with the highest number of cases was Ansai District (20.67%, 62/300), followed by Baota District (19.33%, 58/300) and Zhidan County (17.67%, 53/300). The results of multivariate logistic analysis showed that contact with livestock and unprotected contact were risk factors for brucellosis infection ( OR = 2.81, 6.75, 95% CI: 1.14 - 5.98, 1.23 - 15.72, P < 0.05). Conclusions:From 2019 to 2023, the number of brucellosis cases in Yan'an has been increasing year by year, with a higher incidence among young and middle-aged people. Summer and autumn are the high incidence seasons for the disease, and Ansai District, Baota District, and Zhidan County are key areas for brucellosis prevention and control in Yan'an City. Failure to take protective measures when in contact with livestock can increase the probability of brucellosis infection.

Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.

Objective This study aimed to evaluate the bone integration performance of antibacterial carbon dot(CD)-modified polyether ether ketone(PEEK)in infectious bone defect environments.Methods Guanidine-based CDs(G-CDs)prepared by the melting method combined with dialysis purification were used to modify PEEK implants using polyvinyl butyraldehyde(PVB)by the soaking-drying method(PEEK/PVB-G-CDs).SD rats were divided into the following groups:(1)PEEK-implanted uninfected(PEEK(-)),(2)PEEK/PVB-G-CDs-implanted uninfected(PEEK/PVB-G-CDs(-)),(3)PEEK-implanted infected(PEEK(+)),and(4)PEEK/PVB-G-CDs-implanted infected(PEEK/PVB-G-CDs(+)).A hole(diameter 2 mm,depth 5 mm)was drilled at the lateral condyle of the vertical femur in all rats to simulate a bone defect.Rats in the PEEK(-)and PEEK/PVB-G-CDs(-)groups without infection were injected with 30 μL physiological saline into the bone marrow cavity,and rats in the PEEK(+)and PEEK/PVB-G-CDs(+)groups with infection were injected with 30 μL MRSA bacterial suspension(1.5 × 104 colony-forming units/mL)into the bone marrow cavity.The implantation site was observed using animal-specific X-ray examination at 0,2,and 4 weeks after implantation,and the bone tissue characteristics of the implantation site were evaluated by micro computed tomography(CT)at 6 weeks after surgery.The bone implantation sites in each group of rats were examined by bacterial culture of bone marrow and hematoxylin and eosin staining,Toluidine blue,Goldner trichrome,and immunohistochemical staining.Results X-ray,Micro-CT,bacterial culture of bone marrow,and histopathological analysis confirmed no signs of infection in the PEEK(-)and PEEK/PVB-G-CDs(-)groups and the implants were integrated with the bone defects.Rats in the PEEK/PVB-G-CDs(+)group showed signs of antibacterial activity that effectively controlled the osteomyelitis caused by MRSA and achieved bone integration,while rats in the PEEK(+)group failed to achieve bone integration because of persistent infection.Immunohistochemical staining confirmed lower levels of anti-inflammatory factors such as IL-4 and IL-10 in the PEEK(+)group,and stronger expression of pro-inflammatory factors such as IL-6 and TNF-α compared with the other three groups,indicating that G-CD-modified PEEK inhibited MRSA infection,regulated inflammation levels in the local microenvironment,and promoted bone integration at the site of bone defects.Conclusions Antibacterial G-CDs modified PEEK exhibits excellent bone integration performance,providing a candidate strategy for future clinical treatment of infectious bone defects.

Objective This study aimed to evaluate the bone integration performance of antibacterial carbon dot(CD)-modified polyether ether ketone(PEEK)in infectious bone defect environments.Methods Guanidine-based CDs(G-CDs)prepared by the melting method combined with dialysis purification were used to modify PEEK implants using polyvinyl butyraldehyde(PVB)by the soaking-drying method(PEEK/PVB-G-CDs).SD rats were divided into the following groups:(1)PEEK-implanted uninfected(PEEK(-)),(2)PEEK/PVB-G-CDs-implanted uninfected(PEEK/PVB-G-CDs(-)),(3)PEEK-implanted infected(PEEK(+)),and(4)PEEK/PVB-G-CDs-implanted infected(PEEK/PVB-G-CDs(+)).A hole(diameter 2 mm,depth 5 mm)was drilled at the lateral condyle of the vertical femur in all rats to simulate a bone defect.Rats in the PEEK(-)and PEEK/PVB-G-CDs(-)groups without infection were injected with 30 μL physiological saline into the bone marrow cavity,and rats in the PEEK(+)and PEEK/PVB-G-CDs(+)groups with infection were injected with 30 μL MRSA bacterial suspension(1.5 × 104 colony-forming units/mL)into the bone marrow cavity.The implantation site was observed using animal-specific X-ray examination at 0,2,and 4 weeks after implantation,and the bone tissue characteristics of the implantation site were evaluated by micro computed tomography(CT)at 6 weeks after surgery.The bone implantation sites in each group of rats were examined by bacterial culture of bone marrow and hematoxylin and eosin staining,Toluidine blue,Goldner trichrome,and immunohistochemical staining.Results X-ray,Micro-CT,bacterial culture of bone marrow,and histopathological analysis confirmed no signs of infection in the PEEK(-)and PEEK/PVB-G-CDs(-)groups and the implants were integrated with the bone defects.Rats in the PEEK/PVB-G-CDs(+)group showed signs of antibacterial activity that effectively controlled the osteomyelitis caused by MRSA and achieved bone integration,while rats in the PEEK(+)group failed to achieve bone integration because of persistent infection.Immunohistochemical staining confirmed lower levels of anti-inflammatory factors such as IL-4 and IL-10 in the PEEK(+)group,and stronger expression of pro-inflammatory factors such as IL-6 and TNF-α compared with the other three groups,indicating that G-CD-modified PEEK inhibited MRSA infection,regulated inflammation levels in the local microenvironment,and promoted bone integration at the site of bone defects.Conclusions Antibacterial G-CDs modified PEEK exhibits excellent bone integration performance,providing a candidate strategy for future clinical treatment of infectious bone defects.

Many studies have found a correlation between suicidal behavior (SB) and anhedonia, the main symptom of depression, in terms of both psychological and neurophysiological findings. The purpose of this review is to find the relationship between the two neuroimaging mechanisms, and to provide help for the future study of how the brain imaging changes can promote the mechanism of SB in depression patients with anhedonia symptoms. This review also emphasizes the necessity of intervention for the symptoms of anhedonia when preventing depression from committing suicide. The latest research results were reviewed about anhedonia in depression and magnetic resonance imaging of SB.The results showed that the default network, insula, lateral orbitofrontal gyrus, anterior cingulate gyrus, ventral striatum gyrus, ventral lateral and dorsolateral prefrontal gyrus, thalamus and habenula nucleus were dysfunction in depression with state anhedonia symptoms, affecting SB in terms of mood, execution, reward and aversion processing, especially the low lethal SB.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.