Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y₁₄R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y₁₄R axis in ALF. In this study, hepatic P2Y₁₄R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y₁₄R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y₁₄R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Alb ^cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Lrat ^cre/+ ) mice. Mechanistically, P2Y₁₄R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y₁₄R in ALF and provide an effective adjuvant strategy for treatment of ALF.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

OBJECTIVE: To explore the diagnosis and treatment of acute cerebral infarction following extracorporeal membrane oxygenation (ECMO) therapy in patients with cardiogenic shock to review the literature. METHODS: The clinical data of two patients with cardiogenic shock treated with veno-arterial ECMO (VA-ECMO) complicated with acute cerebral infarction admitted to department of intensive care unit (ICU) of Affiliated Hospital of Guizhou Medical University were retrospectively analyzed and the treatment experience was shared. RESULTS: Case 1 was a 46-year-old male patient who was admitted to the hospital on September 16, 2021, due to "repeated chest tightness, shortness of breath, syncope for 2+ years, and worsened for 15 days. Coronary artery angiography showed 3-vessel coronary artery disease lesions. On October 15, 2021, coronary artery bypass grafting (CABG), pericardial fenestration and drainage, thoracic closed drainage, femoral bypass, thoracotomy exploration, and sternal internal fixation were performed under support of extracorporeal circulation. After surgery, the heart rate was 180-200 bpm, the blood pressure could not be maintained, and the improvement was not obvious after active drug treatment. The right femoral artery and femoral vein were intubated, VA-ECMO support treatment was performed, and the patient was transferred to the ICU. Intra-aortic balloon pump (IABP) was treated on the day of transfer because the circulation could not be maintained. Due to acute cerebral infarction in the left hemisphere and right parieto-occipital lobe, subfalcine herniation, tentorial herniation, the patient ultimately died after withdrawing from ECMO. Case 2 was a 43-year-old male patient who was admitted to the hospital on June 29, 2021, with "fever for 8 days and vomiting for 4 days". Bedside ultrasound showed cardiac enlargement and diffuse wall motion reduction in the left and right ventricles. On June 30, 2021, the patient underwent catheterization through the right femoral artery and femoral vein, VA-ECMO support, and was transferred to ICU for treatment. Acute cerebral infarction on both sides of the cerebellum occurred, and after treatment, the patient was discharged with mild impairment of daily living ability. CONCLUSIONS Strengthen monitoring of anticoagulation; regular neurological examination of patients undergoing ECMO therapy; ECMO under light sedation or awake can be performed if the condition permitsif the condition permits, perform light sedation or awake ECMO, which helpful for the early detection of nervous system injury.
Male ; Humans ; Middle Aged ; Adult ; Shock, Cardiogenic/therapy* ; Extracorporeal Membrane Oxygenation ; Retrospective Studies ; Coronary Artery Bypass/adverse effects* ; Cerebral Infarction/therapy*

Objective: To investigate the current status of knowledge and practice pertaining to nosocomial infection control among medical professionals in grassroots healthcare institutions, so as to provide the evidence of improving the level of infection control in grassroots healthcare institutions. Methods: All medical professionals working in grassroots healthcare institutions in Pukou District, Nanjing City, were enrolled. The participants' demographic features and knowledge and practice of nosocomial infection control were collected using self-designed questionnaires and descriptively analyzed. Results: A total of 402 participants were enrolled, included 116 men ( 28.86% ) and 286 women ( 71.14% ). The respondents were predominantly at ages of 41 years and older ( 187 subjects, 46.52% ), with bachelor and above as the predominant educational level ( 200 subjects, 49.75% ) and intermediate title and above as the predominant professional title ( 168 subjects, 41.79%) , and there were 236 participants ( 58.71% ) with the length of service for more than 10 years. The awareness rate of nosocomial infection control knowledge was 56.22% among medical professionals working in grassroots healthcare institutions, with the highest awareness for COVID-19 prevention and control ( 89.55% ) and the lowest awareness for the key aspects in nosocomial infection control ( 39.55% ). The formation rate of implementing nosocomial infection control practices was 84.08%, with a low rate for “Implement satisfactorily the isolation interventions for patients with multidrug resistant bacteria” ( 71.14% ) and “Implement satisfactorily the control measures for nosocomial infections in key departments and key aspects”( 64.68% ). Conclusions Low levels are seen in the awareness of nosocomial infection control, behaviors of multidrug resistance management and key aspects in nosocomial infection control among medical professionals in grassroots healthcare institutions in Pukou District.

Objective:To evaluate the early side effects and influencing factors in patients undergoing intensity-modulated radiation therapy after cervical cancer surgery.Methods:A retrospective analysis of 106 patients with cervical cancer who underwent postoperative intensity-modulated radiation therapy in our hospital from January 2014 to December 2017 was conducted. The occurrence of toxic and side effects were summarized, and the related clinical indicators were analyzed using univariate and multivariate analyses.Results:The 3-year overall survival rate was 88.1%, and the 3-year progression-free survival rate was 84.8%. The incidence of acute hematologic toxicity greater than grade 3 was 33%. The incidence of early intestinal reactions was 35%, of which only 1.8% was greater than grade 3. Univariate analysis demonstrated that severe acute hematologic side effects were statistically significant ( χ2=1.789-17.895, P<0.05) with the level of hemoglobin before radiotherapy, radiation in the abdominal aortic lymphatic drainage area or not, an increase of local radiotherapy dose in the target area, and chemotherapy or not. Multivariate analysis showed that concurrent chemotherapy significantly increased the incidence of severe acute hematologic toxicity ( χ2=3.929, P<0.05). Conclusions:In patients with cervical cancer undergoing postoperative intensity-modulated radiation therapy, grade 3 and greater toxic side effects are mainly related to hematological toxicity, and the incidence of severe bowel toxicity in the early stage is low.

Objective To evaluate 18F-fluorodeoxyglucose (FDG) PET/CT in the rabbit model of vulnerable plaques by correlation with 99Tcm-Arg-Gly-Asp (RGD) SPECT/CT imaging,lipid levels,pathological and immunohistochemical results.Methods Sixteen male New Zealand white rabbits were randomly divided into normal diet group (group A,n =4),stable plaque group (group B,n =4) and vulnerable plaque group (group C,n =8) using completely random grouping method.The animals were given abdominal aorta sham operation (groups A and B) or balloon injury of the abdominal aorta (group C) 2 weeks after feeding.Animals were injected with 18F-FDG and 99Tcm-RGD respectively at the end of 4,8 and 12 weeks.PET/CT was performed at 1,2 and 3 h post-injection.SPECT/CT was performed at 30 min post-injection.One rabbit was sacrificed at the end of 4 and 8 weeks after imaging studies,respectively.The others were sacrificed at the end of 12 weeks after imaging studies.All abdominal aortas were harvested.Pathology and immunohistochemistry analysis were performed.The data were analyzed by one-way analysis of variance and Pearson correlation analysis.Results There was no uptake in any group at 4th week and no uptake in group A or group B at 8th week.There was mild uptake in group B at 12th week and group C at 8th week.There was intense uptake in group C at 12th week,whereas both mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) were significantly higher than the other two groups (F values:7.952,14.279,both P＜0.05).In group C,SUVmax(0.43±0.08,0.68±0.06,1.74±0.63) and SUV (0.37±0.03,0.56±0.03,1.26+0.23) had significant difference at 3 h post-injection for imaging at 4th,8th and 12th week (F values:10.939,39.747,both P＜0.05).At 12th week,there was a strong correlation between the uptake of 18 F-FDG and target/non-target (T/NT) ratio of 99Tcm-RGD in all groups(r values:0.748,0.709,both P＜0.05).Histopathology results showed that the plaques had rich macrophages and a small amount of smooth muscle cells in group C,little macrophages in group B,while no macrophages in group A.Conclusion 18F-FDG PET/CT might be an effective noninvasive method for early assessment of aortic vulnerability to atherosclerotic plaque.

Objective To investigate the value of pulmonary ventilation/ perfusion (V/ Q) SPECT in evaluation of anticoagulant therapy for patients with pulmonary embolism (PE) and identify factors which may affect the therapy. Methods From July 2014 to December 2016, sixty-three patients (23 males, 40 females, age (60±14) years), who were clinically diagnosed as PE and underwent V/ Q SPECT before and after anticoagulant therapy, were recruited retrospectively in this study. According to the percentage of lung perfusion defect (PD) out of total lung volume, the patients were divided into mild (<20％) PE, moderate (20％-50％) PE, and severe (>50％) PE groups. The lung PD decreased≥50％ after anticoagulant thera-py and no new PD detected was defined as the standard of effective therapy, otherwise the treatment were defined as ineffective. Data of different groups were compared. Factors that may predict the severity of PD or affect the treatment were analyzed. χ2 test and logistic regression were used for data analysis. Results PE were detected in 476 pulmonary segments and sub segments. The distribution of PE in different lung lobes had no statistically significant difference ( χ2 = 4. 995, P > 0. 05). More pulmonary arterial hypertension (PAH) were detected in patients with severe PE (80％, 12/ 15) and moderate PE (66.7％,16/ 24) in comparison with patients with mild PE (41.7％,10/ 24; χ2 = 7.062, P<0.05). The occurrence of PAH was related to the severity of PD, with odds ratio (OR) value of 2.680 (95％ CI: 1.115-6.446, P<0. 05).PAH was an independent risk factor for treatment effect (OR value: 3.134(95％ CI: 1.341-7. 324), P<0. 05). Conclusions V/ Q SPECT has an important value for evaluating the effect of anticoagulant therapy and guiding individual therapy. The more extent of PE involved, the higher prevalence of PAH. Anticoagu-lant therapy may be ineffective in PE patients with moderate or severe PAH.

Objective To investigate the feasibility of a novel molecular probe 99Tcm-3P4-RGD2 in evaluating arterial plaque stability after atorvastatin intervention in rabbits with SPECT/CT. Methods Eighteen male New Zealand rabbits were randomly divided into group A (stable plaque), group B (vulnerable plaque), and group C (vulnerable plaque with statin intervention). All rabbits were fed with high-fat food for 12 weeks. After high-fat feeding for two weeks, sham surgery was performed on group A. In the meantime, abdominal aorta injury was performed on group B and group C. After that, rabbits of group C were given oral atorvastatin (2.5 mg·kg-1·d-1). 99Tcm-3P4-RGD2 SPECT/CT imaging was performed on each group at the end of 4, 8 and 12 weeks. T/NT ratios were calculated. Animals were sacrificed at the end of 12 week after imaging studies. The abdominal aortas were collected, imaged with SPECT/CT, and evaluated by pathological HE staining and immunohistochemical analysis. MVD was calculated. Differences among 3 groups were analyzed using one-way analysis of variance. Results There was no significant radioactive uptake in the abdominal aortas of three groups on the 4th week′s imaging. The radioactive uptake in abdominal aortas increased slightly on the 8th week, with the highest radioactive uptake in group B. The radioactivity in abdominal aortas of the 3 groups maintained increasing on the 12th week, with T/NT ratios of 1.579±0.217, 1.873±0.226 and 1.524±0.237, respectively (F=8.984, P<0.05). In ex vivo abdominal aorta images, especially images of group B, radioactivity in lesion sites was higher than that in normal tissue. Accordingly, results of HE staining showed that artery plaques of group A and group C were grade Ⅱ and group B was grade Ⅳ. The MVD of group A, B and C was 8.17±1.17, 15.86±1.07 and 7.17±1.60, respectively (F=9036, P<0.05). Conclusion 99Tcm-3P4-RGD2 SPECT/CT imaging has a high sensitivity in the evaluation of arterial plaque stability after statin intervention in rabbits.

Objective To summarize our experiences in the long-term continuous maintenance of the peripherally inserted central catheter (PICC) in a patient with intestinal fistula.Method The systematic holistic nursing care has been provided according to the nursing practices to a patient with intestinal fistula since 2006,during which eitht PICCs were used successively.Results The eight PICCs were placed for 3-14 months.The 1 st,3rd,5th,and 7th cathers were retained for 12,13,11,and 14 months.The second catheter was retained for 6 months,and then removed due to increased body temperature (38.7℃).The 4th cather was retained for 3 months,then catheter-related bloodstream infection was suspected due to high body temperature (39℃) ; culture for fungi at the tip showed positive results.The 6th catheter was retained for 7 months,inserting from jugular vein to the superior vena cava; however,it was removed due to puncture point local purulent changes at the puncture site.The 8th catheter was applied for 8 months,but was rmoved due to tube occlusion,which responded poorly to urokinase.Conclusion The application of PICC in patients with fistula can relieve the pain and improve the quality of life.