PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Objective To investigate the cumulative incidence of recurrence(CIR)in children with acute lymphoblastic leukemia(ALL)after treatment with the Chinese Children's Cancer Group ALL-2015(CCCG-ALL-2015)protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019.CIR was calculated,and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia(B-ALL)were analyzed.Results Among the 852 children with ALL,146(17.1%)experienced recurrence,with an 8-year CIR of 19.8%±1.6%.There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group(P>0.05).For the 146 children with recurrence,recurrence was mainly observed in the very early stage(n=62,42.5%)and the early stage(n=46,31.5%),and there were 42 children with bone marrow recurrence alone(28.8%)in the very early stage and 27 children with bone marrow recurrence alone(18.5%)in the early stage.The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene(HR=4.177,95%CI:2.086-8.364,P<0.001)and minimal residual disease≥0.01%on day 46(HR=2.013,95%CI:1.163-3.483,P=0.012)were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol,mainly bone marrow recurrence alone in the very early stage and the early stage,and minimal residual disease≥0.01%on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Based on the views of FAN's Eight Dynamic-Static Sequential Methods,Professor FAN Guan-Jie believes that the obesity has the pathological factor of blood stasis in addition to qi deficiency and phlegm-damp.The compatibility of blood-activating and stasis-removing drugs for the treatment of obesity is accorded to the progression of the disease.In the clinic,Crataegi Fructus associated medicinal cluster of activating blood and removing stasis is usually recommended.The medicinal cluster is with Crataegi Fructus as the chief medicinal,and is compatible with drug pairs of Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos and Moutan Cortex-Paeoniae Radix Rubra.Crataegi Fructus associated medicinal cluster is able to treat qi and blood simultaneously,mainly aimed at removing blood stasis,supplemented by nourishing blood,promoting qi and blood movement,and invigorating spleen and stomach,which has the features of simultaneous dispersing and astringency,and proper combination of static therapy and dynamic therapy,and is suitable for obese patients with blood stasis obstruction in the vessels.

The number of type 2 diabetes(T2DM)accounts for more than 90％of all Diabetes mellitus(DM).The decrease of islet β cell mass and dysfunction are the core links of T2DM.With the prolongation of the course of disease,the number and function of β cells are gradually attenuated,and the damage mechanism has not been elucidated.At present,it is believed that it is closely related to metabolic stress,abnormal regulation of insulin secretion,changes in islet microenvironment,mitochondrial damage,glycolipid toxicity and dedifferentiation of islet β cells.Therefore,the mechanism of islet β cell damage in T2DM is summarized and elaborated in order to provide some reference for the precise intervention of T2DM.

Objective To investigate the knowledge and behavioral status of foot care among patients with type 2 diabetes in Xinjiekou Community in Beijing and analyze its influencing factors. Methods A convenient sampling method was used to select 278 diabetes patients from Xinjiekou Community in Beijing for questionnaire surveys, which included general information, foot care knowledge, and behaviors of the patients. Results The average score of foot care knowledge among the 278 patients was (71.65±14.59), indicating a moderate level overall. The average score of foot care behavior was (48.83±8.83), indicating a poor level overall. Multivariate stepwise regression analysis showed that gender, duration of diabetes, and whether the patients had received foot care education or not were independent influencing factors for both the foot care knowledge score and the foot care behavior score among community diabetes patients (P < 0.05). Pearson correlation analysis showed that a positive correlation between foot care knowledge and foot care behavior among community diabetes patients was observed(r=0.593, P < 0.001). Conclusion The level of foocare knowledge among diabetes patients in this community in Beijing is moderate, while the status of foot care behaviors is not optimistic. Community healthcare professionals should strengthen health education on foot care, improve patients' knowledge of foot care and compliance with foot care behaviors, and pay attention to male patients and those with a shorter duration of diabetes to reduce the occurrence of diabetic foot.

Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
Humans ; Liposomes ; Hepatic Stellate Cells ; Glycyrrhetinic Acid/pharmacology* ; Liver ; Liver Cirrhosis/genetics* ; Collagen/pharmacology*