[Improved synthesis process of optical-magnetic bimodal probe of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes].

OBJECTIVE: To improve the methods to synthesize and purify of optical-magnetic bimodal molecular probe of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluorescein thioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes. METHODS: Target compound (7), optical-magnetic bimodal molecular molecular probe, was synthesized by the use of 1, 4, 7, 10-tetraazacyclododecane (1) as starting material via substitution reaction, hydrolysis reaction, coupling reaction and complexation reaction with metal. RESULTS: The synthetic route of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes was improved. The optical-magnetic bimodal molecular probes were synthesized by substitution reaction, hydrolysis reaction, coupling reaction and complex reaction with metal respectively. For the improved route, the total yield could reach 34.6% which was higher than the original route (18.0%). The structures of those compounds were identified by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and mass spectrometry. The improved route could avoid the uncontrollable disadvantage of the substitution reaction, this process could reduce the formation of impurities and made the purification process easier, and in the aspect of purification and separation, the preparative high-performance liquid chromatography with less sample loading and high cost was improved to a column chromatography with many sample loads and being easy to operate. Therefore, the use of column chromatography could be more conducive to mass production of the optical-magnetic bimodal molecular molecular probe. CONCLUSION: The improved synthetic route improves the controllability of the reaction conditions and makes it easier to purify and separate the compounds. At the same time, the improved synthetic route can increase the total yield significantly. The optical-magnetic bimodal molecular probe can combine the living magnetic resonance imaging with the in vitro optical imaging to realize the dual synchronous detection of magneto-optics, so that the detection results of the living magnetic resonance imaging and the in vitro optical imaging are mutually verified. In other words, this synthetic optical-magnetic bimodal molecular probe will make the experimental results more accurate and reliable. In subsequent biological experimental studies, the optical-magnetic bimodal molecular probe can be applied to related research of brain structure and function, and the probe can be used for the brain-related diseases researches, such as brain tumors. after intravenous administration, and thus the optical-magnetic bimodal molecular probe can play an important role in medical treatment of brain tumors and cerebrovascular diseases.

[Gene-age interaction study of breast cancer prognosis based on epigenomic data].

Objective: Exploring gene-age interactions associated with breast cancer prognosis based on epigenomic data. Methods: Differential expression analysis of DNA methylation was conducted using multiple independent epigenomic datasets of breast cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The false discovery rate (FDR) method was used for multiple corrections, retaining differentially methylated sites with q-FDR≤0.05. A three-stage analytic strategy was implemented, using a multivariable Cox proportional hazards regression model to examine gene-age interactions. In the discovery phase, signals with q-FDR ≤ 0.05 were screened out using TCGA-BRCA database. In validation phaseⅠ, the interaction was validated using GSE72245 data, with criteria of P≤0.05 and consistent effect direction. In validation phaseⅡ, the signals were further validated using GSE37754 and GSE75067 data. A prognostic prediction model was constructed by incorporating clinical indicators and interaction signals. Results: The three-stage analytic strategy identified a methylation site (cg16126280EBF1), which interacted with age to jointly affect the overall survival time of patients (interaction HR= 1.001 1,95%CI:1.000 7-1.001 5,P<0.001). Stratified analysis by age showed that the effect of hypermethylation of cg16126280EBF1 was completely opposite in younger patients (HR=0.550 5, 95%CI: 0.383 8-0.789 6, P=0.001) and older patients (HR=2.166 5, 95%CI: 1.285 2-3.652 2, P=0.004). Conclusions: The DNA methylation site cg16126280EBF1 exhibits an interaction with age, jointly influencing the prognosis of breast cancer in a complex association pattern. This finding contributes new population-based evidence for the development of age-specific targeted drugs.

[Clinical features and outcomes of cancer-related versus non-cancer-related sepsis in pediatric intensive care unit].

Objective: To compare the clinical features and outcomes of cancer-related and non-cancer-related sepsis in children who were admitted pediatric intensive care unit (PICU). Methods: The clinical history of patients with sepsis, who were admitted to PICU in Shanghai Children's Hospital, Shanghai Jiao Tong University from August 2016 to July 2019, were retrospectively reviewed. A total of 768 patients were divided into the cancer-related sepsis group (135 cases) and the non-cancer-related sepsis group (633 cases). The patients in the cancer-related group were further categorized into three subgroups including hematological malignancy (80 cases), solid tumor (43 cases) and hemophagocytic lymphohistiocytosis (HLH) (12 cases). The variables of clinical features, laboratory tests, pathogens, management strategies and in-hospital mortality were compared between the two groups by student t test, Mann-Whitney U test or Chi-square test. Results: The patients with cancer-related sepsis accounted for 17.6% of all patients (135/768). Regarding the site of initial infection, the incidence of gastrointestinal infection (43.0% (58/135) vs. 28.6% (181/633), χ(2)=10.718, P=0.001), blood stream infection (29.6% (40/135) vs. 17.1% (108/633), χ(2)=11.297, P=0.001) and skin and soft tissue infection (22.2% (30/135) vs. 4.1% (26/633), χ(2)=54.013, P<0.01) were higher in the patients with cancer-related sepsis than in those with non-cancer-related sepsis. On first PICU admission, the levels of hemoglobin (71 (61, 83) vs. 106 (92, 116) g/L, Z=13.594, P<0.01), white blood cell (1.4 (0.3, 5.2) vs. 9.8 (5.8, 15.1)×10(9)/L, Z=11.213, P<0.01), platelet count (51 (15, 121) vs. 286 (192, 384)×10(9)/L, Z=13.336, P<0.01), CD19(+)cells (0.106 (0.008, 0.274) vs. 0.325 (0.224, 0.454), Z=6.555, P<0.01), and neutrophil (0.449 (0.170, 0.730) vs. 0.683 (0.537, 0.800), Z=5.974, P<0.01) were significantly lower in patients with cancer-related sepsis; however, the levels of C-reactive protein (82 (25, 155) vs. 36 (11, 86) mg/L, Z=-5.257, P<0.01), procalcitonin (1.5 (0.3, 12.0) vs. 0.8 (0.2, 4.0) µg/L, Z=-2.767, P=0.006), CD8(+)cells (0.329 (0.253, 0.514) vs. 0.209 (0.156, 0.275), Z=-5.699, P<0.01), interleukin (IL) -6 (0.1 (0.1, 522.4) vs. 0.1 (0.1, 0.1) ng/L, Z=-2.747, P=0.006), IL-8 (0.1 (0.1, 177.0) vs. 0.1 (0.1, 4.5) ng/L, Z=-2.087, P=0.037), and IL-10 (0.1 (0.1, 42.7) vs. 0.1 (0.1, 6.6) ng/L, Z=-2.148, P=0.032) were significantly higher in patients with cancer-related sepsis. Similarly, the rate of continuous renal replacement therapy (CRRT) (34.8% (47/135) vs. 16.9% (107/633), χ(2)=26.267, P<0.01) and the use of intravenous immunoglobulin (IVIG) (83.0% (112/135) vs. 66.2% (419/633), χ(2)=14.667, P<0.01) were significantly higher in cancer-related sepsis group. Moreover, the incidence of co-infection with fungi was also higher in cancer-related sepsis group (14.1% (19/135) vs. 0.5%(3/633), χ(2)=73.965, P<0.01), and so was the number of multiple organ dysfunction (3 (2, 5) vs. 2 (1, 3), Z=-6.988, P<0.01). Finally, the in-hospital mortality rate of cancer-related sepsis and non-cancer-related sepsis were 36.3% (49/135) and 9.3% (59/633), respectively, also significantly different (χ(2)=67.000, P<0.01). There was no difference in the in-hospital mortality among children with hematologic tumors, solid tumors and HLH (35.0% (28/80) vs. 32.6% (14/43) vs. 7/12, χ(2)=2.838, P=0.242). Conclusions: The site of initial infection, inflammatory markers on PICU admission, and co-infection pathogen during hospitalization are different between patients with cancer-related sepsis and non-cancer-related sepsis. Besides, the in-hospital mortality of cancer-related sepsis is about 4-fold that of non-cancer-related sepsis. The monitoring of clinical features and organ dysfunction, and timely treatment are crucial for cancer-related sepsis.

[Laboratory study on the relationship between drinking water and hepatoma--quantitative evaluation using hepatic gamma-GT method].

One to two-month-old male Fischer 344 (F-344) rats were used in this investigation. The experiment was devised simulating the Two-stage Hepatocarcinogenesis Model described by Pitot. Quantitative stereological method was applied to evaluate the gamma-GT enzyme altered foci (EAF) in examined liver slides. The results showed that pond-ditch water had an enhancement effect on the expression of gamma-GT in the livers of male F-344 rats, where as well water had no such effect. When AFB1 was given alone to the male F-344 rats after partial hepatectomy, there was no effect on gamma-GT, if it was followed by pond-ditch water the rats would express high frequency of EAF. In this experiment the effect of organochlorinated pesticide DDT on hepatic gamma-GT was also studied. It showed a strong influence on the quantity and size of EAF.

Comparison of medial and lateral septal neuron activity during performance of spatial tasks in rats.

The septal complex, having close and reciprocal connections with the hippocampus, is known to play an important role in learning and memory. Anatomically, the septal complex is divided into the medial and lateral areas (MS and LS). In the present study, in order to elucidate functional differences between the MS and LS, we recorded single unit activity in the MS or LS and electroencephalogram (EEG) in the hippocampus simultaneously while the rats performed the following 2 spatial tasks in an open-field chamber. In task 1, the rat received rewarding intracranial electrical stimulation (ICES) when it entered in a reward place that was set randomly in the open field in each trial. In task 2, the rat received rewarding ICES when it alternately visited two fixed reward places in the open field. Unit activity was analyzed in relation to the pattern of hippocampal EEG, and rat's location, locomotion direction and locomotion speed in the spatial tasks. A total of 47 neurons were recorded in the septal complex (MS, 19; LS, 28). The majority of neurons with activity correlated with hippocampal EEG were found in the MS (14/19). All of the neurons with place-related activity (an increase in unit activity when the rat was in a specific location in the open field) were found in the LS (n = 15). The majority of neurons with direction-related activity were found in the LS (18/23). Twenty-one neurons displayed speed-related activity (MS, 9; LS, 12). The present results indicate that (1) the MS is directly involved in the formation and control of hippocampal EEG patterns, and (2) the LS is important for the processing and integration of spatial information in the environment.

Percutaneous probe reduction of frontal fractures of the humeral capitellum.

Nine frontal fractures of the humeral capitellum treated by percutaneous probe reduction are reported. Most of the fractures were percutaneously reduced with a Steinmann pin inserted along the lateral border of the biceps tendon. To prevent redisplacement of the fragment, the elbow joint was first flexed more than 90 degrees with plaster immobilization for two weeks. The favorable results obtained with this method are due to reduced surgical trauma to local tissues and good reduction of the fracture. The percutaneous probe reduction should be considered for frontal fracture of the humeral capitellum before open reduction is performed.