Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

Objective: To investigate the mechanism of Anemoside B4 (AB4) on glutamine metabolism in oral li- chen planus (OLP) epithelial cells via the nitric oxide synthase 3 (NOS3)-dihydrofolate reductase (DHFR) axis . Methods: Bioinformatics analysis was performed to identify the intersection of molecular targets of OLP , AB4 , and genes related to glutamine metabolism . A lipopolysaccharide ( LPS)-induced HOK-16B model of OLP was estab- lished . HOK-16B were divided into Ctrl group , OLP group , AB4 group , OLP + oe-NOS3 group , OLP + sh-NOS3 group , OLP + sh-NOS3 + oe-DHFR group , and OLP + sh-NOS3 + AB4 group . Cell proliferation was detected by cell counting kit-8 (CCK-8) ; cell apoptosis was detected by TdT-mediated dUTP Nick-End Labeling ( TUNEL) ; inflammatory factors iInterleukin (IL)-1β, tumor necrosis factors-α ( TNF-α) concentrations in cell supernatants were measured using enzyme-linked immunosorbent assay (ELISA) kits; glutamine uptake and glutamate produc- tion were determined using kits; and the protein expression of alanine-serine-cysteine transporter2 ( ASCT2) and glutamine synthase (GLS) was assessed by Western blot. Results: Bioinformatics analysis of molecular targets of OLP , AB4 , and genes related to glutamine metabolism revealed three intersection targets : NFE2L2 , NOS1 , and NOS3 . Compared with the Ctrl group , the OLP group exhibited decreased HOK-16B cell viability (P < 0. 001) , increased apoptosis rate (P < 0. 01) , upregulated concentrations of IL-1βand TNF-α(P < 0. 001) , elevated glu- tamine uptake and glutamate production (P < 0. 01) , and enhanced expression of ASCPT2 and GLS proteins (P < 0. 001) . Compared with the OLP group , the AB4 group showed improved cell viability (P < 0. 05) , reduced apop- tosis rate and release of IL-1βand TNF-α(P < 0. 05) , decreased glutamine uptake and glutamate production (P < 0. 05) , and downregulated expression of ASCPT2 and GLS proteins ( P < 0. 001) . Compared with the OLP group , the OLP + oe-NOS3 group had increased HOK-16B cell viability (P < 0. 01) , reduced apoptosis rate (P < 0. 05) , decreased concentrations of IL-1βand TNF-α(P < 0. 05) , lowered glutamine uptake and glutamate pro- duction (P < 0. 05) , and weakened expression of ASCPT2 and GLS proteins (P < 0. 01) ; whereas the OLP + sh- NOS3 group had decreased HOK-16B cell viability ( P < 0. 05) , increased apoptosis rate ( P < 0. 05) , elevated concentrations of IL-1βand TNF-α ( P < 0. 01 ) , increased glutamine uptake and glutamate production ( P < 0. 05) , and enhanced expression of ASCPT2 and GLS proteins (P < 0. 001) . Compared with the OLP + sh-NOS3 group , both the OLP + sh-NOS3 + oe-DHFR group and the OLP + sh-NOS3 + AB4 group showed increased HOK- 16B cell viability (P < 0. 001) , reduced apoptosis rate (P < 0. 05) , decreased concentrations of IL-1βand TNF-α (P < 0. 01) , lowered glutamine uptake and glutamate production ( P < 0. 05) , and weakened expression of AS- CPT2 and GLS proteins ( P < 0. 05) . Conclusion AB4 inhibits the progression of OLP by mediating glutamine metabolism via the regulation of the NOS3-DHFR axis .

Objective To investigate the role of H9c2-derived exosomes in regulating angiogenesis in rat cardiomyocytes under hypoxia.Methods The hypoxia model of H9c2 cells was prepared by mixed gas method(the hypoxia model group),and the normal cultured cells were used as the control group.The exosomes secreted by the two groups of cells were extracted respectively.The concentration and particle size of exosomes were detected by nanoparticle tracking analysis.The morphology and size of exosomes were detected by transmission electron microscopy.Western blot assay was used to verify the exosome marker proteins.The hypoxia model of human umbilical vein endothelial cells(HUVEC)was established.HUVECs were incubated with H9c2 exosomes and divided into the normoxia group,the hypoxia group,the hypoxia+normal H9c2 exosomes(EXO-C)group and the hypoxia+hypoxia H9c2 exosomes(EXO-M)group.The proliferation,migration and tube formation of HUVECs were detected by CCK-8 method,cell scratch test and Matrigel in vitro three-dimensional forming test.Results The results of exosome identification showed that the particle concentration of H9c2 exosome samples was 1×107-1×1012 particles/mL and the particle size was 40-160 nm in the normoxia group and the hypoxia group.The morphological characteristics were spherical or saucer-like structure,uniform in size and complete in shape.Exosome marker proteins TSG101,CD63 and CD9 were expressed,and there was no expression of negative protein Calnexin.Compared with the normoxic group,the proliferation ability,migration area and migration rate of HUVEC were significantly decreased in the hypoxic group,and the length of tube,the number of branches and the number of nodes were decreased(P＜0.01).Compared with the hypoxia group,the proliferation ability of HUVEC cells was decreased,the migration area was decreased,the migration rate was decreased and the length and number of branches involved in tube formation were further decreased in the EXO-M group(P＜0.05).Compared with the EXO-C group,the proliferation ability of the EXO-M group decreased,the cell migration area decreased and the migration rate decreased(P＜0.01).Conclusion Exosomes derived from hypoxic H9c2 can inhibit the proliferation,migration and tube formation of HUVEC.

To explore the feasibility of applying magnetic stimulation technology to the movement control of animal robots, the influence of coil radius, number of turns and other factors on the intensity, depth and focus of magnetic stimulation was simulated and analyzed for robot pigeons. The coil design scheme was proposed. The coil was placed on the head and one of the legs of the pigeon, and the leg electromyography (EMG) was recorded when magnetic stimulation was performed. Results showed that the EMG was significantly strengthened during magnetic stimulation. With the reduction of the output frequency of the magnetic stimulation system, the output current was increased and the EMG was enhanced accordingly. Compared with the brain magnetic stimulation, sciatic nerve stimulation produced a more significant EMG enhancement response. This indicated that the magnetic stimulation system could effectively modulate the functions of brain and peripheral nerves by driving the coil. This study provides theoretical and experimental guidance for the subsequent optimization and improvement of practical coils, and lays a preliminary theoretical and experimental foundation for the implementation of magnetic stimulation motion control of animal robots.
Animals ; Columbidae ; Robotics ; Motion ; Brain ; Magnetic Phenomena

【Objective】 To investigate the situation of whole blood collection in Tianjin after COVID-19 prevention and control measures were fully lifted. 【Methods】 The relevant data on whole blood collection of voluntary blood donors in Tianjin 15 days before Spring Festival (2023.01.07-2023.01.21, when China has managed COVID-19 with measures against Class B infectious disease instead of Class A infectious diseases) and 15 days before Spring Festival in 2018 (2018.02.01- 2018.02.15) and 2019 (2019.01.21-2019.02.04) before the breakout of COVID-19 were retrospectively collected and compared. 【Results】 The comparison between the above period in 2023, 2018 and 2019 was as follows: the number of blood donors was 6 124 vs 3 940 vs 4 069; blood collection volume (U) was 9 623 vs 7 378 vs 7 808; the proportion of first-time blood donors, local blood donors and group blood donors was 69.17% (4 236/6 124) vs 65.86% (2 595/3 940) vs 62.05% (2 525/4 069), 59.31% (3 632/6 124) vs 23.27% (9170) vs 18.19% (740/4 069) and 43.42% (2 659/6 124) vs 8.05% (317/2 595) vs 0.15% (6/4 069) (all P<0.05). 【Conclusion】 The adjustment of COVID-19 prevention and control policy has a significant impact on voluntary blood donation, and the corresponding adjustment of blood donor recruitment strategy in blood centers should be conducted to increase the whole blood collection.

ABSTRACT OBJECTIVE To investigate the current situation of pediatric pharmacist-managed clinic in China, and to provide reference for pediatric pharmacist-managed clinic construction and improvement. METHODS Domestic Children's hospitals, Women's & Children's Hospital, and general hospitals with pediatric unit were selected as the survey objects, questionnaires were distributed through the Wenjuanxing Application, and SPSS 26.0 was used to describe the data. The development of pediatric pharmacist-managed clinic, the qualification of visiting pharmacists, the situation of post training and training needs were analyzed. RESULTS A total of 101 valid questionnaires were collected. Pediatric pharmacist-managed clinics had been set up in 55(54.5%) hospitals, of which 35 were independent pharmacists' clinics, and most had well medical document and patient management processes. However, about 70% of hospitals did not charge registration fees, and more than half of hospitals had fewer than 5 patient-visits per day. 85.5% of the hospitals were visited by clinical pharmacists, and about half of them were senior clinical pharmacists with more than 10 years of working experience. But only 3.6% of visiting pharmacists had the right of specific prescription. In 101 hospitals relevant post training for pharmacists had been carried out in 36 hospitals, of which 25 hospitals had set up pharmacist-managed clinic. In addition to pharmaceutical expertise, more than 50% of pharmacists had a strong demand for the improvement of physician-patient communication and problem-solving ability, and 30%-40% of the demand was focused on the collection of medication history, psychological counseling ability, and case-based learning in the pharmacist-managed clinic. CONCLUSION At present, the domestic pediatric pharmacist-managed clinic shows a vigorous development trend, however, there are insufficient registration fees, visits, and post training. Appropriate service methods of pediatric pharmacist-managed clinic should be actively explored, and a pediatric specialized training system for should be well constructed to improve the competency.

Coronary angiography (CAG) as a typical imaging modality for the diagnosis of coronary diseases hasbeen widely employed in clinical practices. For CAG-based computer-aided diagnosis systems, accurate vessel segmentation plays a fundamental role. However, patients with bradycardia usually have a pacemaker which frequently interferes the vessel segmentation. In this case, the segmentation of vessels will be hard. To mitigate interferences of pacemakers and then extract main vessels more effectively in CAG images, we propose an approach. At first, a pseudo CAG (pCAG) image is generated through a part of a CAG sequence, in which the pacemaker exists. Then, a local feature descriptor is employed to register the relative location of pacemaker between the pCAG image and the target CAG image. Finally, combining the registration result and segmentation results of main vessels and pacemaker, interferences of pacemaker are removed and the segmentation of main vessels is improved. The proposed method is evaluated based on 11 CAG images with pacemakers acquired in clinical practices. An optimization ratio of the Dice coefficient is 12.04%, which demonstrates that our method can remove overlapping pacemakers and achieve the improvement of main vessel segmentation in CAG images.Our method can further become a helpful component in a CAG-based computer-aided diagnosis system, improving its diagnosis accuracy and efficiency.
Humans ; Coronary Angiography/methods* ; Diagnosis, Computer-Assisted ; Pacemaker, Artificial ; Image Processing, Computer-Assisted/methods* ; Algorithms

Background::Contrast-enhanced ultrasound (CEUS) can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion. This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) with or without CEUS assessment.Methods::Clinical, imaging, and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital, with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated. Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy. According to FNA cytology diagnoses, we combined non-diagnostic, neoplastic, and negative cases into a negative category. The positive category included malignant, suspicious, and atypical cases. The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of US-FNA were evaluated between the two groups.Results::This study enrolled 107 male and 74 female patients (average age: 60 years). There were 58 cases in the US group and 123 cases in the CEUS group. No statistically significant differences in age, gender, or lesion size were found between the two groups. The diagnostic accuracy of the CEUS group was 95.1% (117/123), which was higher than the 86.2% (50/58) observed in the US group ( P = 0.036). The sensitivity, specificity, PPV, and NPV of the CEUS group were increased by 7.5%, 16.7%, 3.4%, and 18.8%, respectively, compared with the US group. However, the differences of the two groups were not statistically significant. Conclusions::Compared with the conventional US, the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy, especially for some complicated FNA cases.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

Objective:To investigate the effect of hemoglobin (Hb) volatility on cardiovascular prognosis in peritoneal dialysis (PD) patients.Methods:Retrospective cohort study was designed. Patients undergoing stable PD for more than 3 months and followed up regularly for at least 1 year were enrolled from May 1, 2013 to October 31, 2014 in the General Hospital of Ningxia Medical University. According to the Hb variation based on the mean changes in Hb standard deviation at 1 month, 3 months, 6 months, 12 months over baseline Hb, all patients were divided into low volatility group (≤10 g/L), moderate volatility group (>10-20 g/L) and high volatility group (>20 g/L), and baseline information were compared among these groups. Kaplan-Meier survival analysis and Cox regression equation were used to analyze the relationship between Hb variation and cardiovascular mortality and all-cause mortality. Besides, the patients were divided into qualified group (Hb≥110 g/L) and substandard group (Hb<110 g/L) by the Hb level at the study endpoint (cardiovascular death and all-cause death) according to KDIGO guidelines and relevant literature. Cox regression analysis was used to analyze the relationship between Hb variation and cardiovascular death in qualified group or substandard group. Multivariate linear regression analysis was used to analyze the related factors of Hb fluctuation in PD patients.Results:A total of 267 patients were enrolled. There were 160 males (59.93%) in this study. The age was (52.66±13.72) years old, and the median dialysis age was 37(21, 61) months. The patients' baseline Hb (before dialysis) was (80.16±14.89) g/L and at the end of the study Hb was (105.34±22.08) g/L. Body mass index and baseline Hb levels in the high volatility group were lower than those in low volatility group and moderate volatility group (all P<0.05). Both moderate and high volatility groups had lower estimated glomerular filtration rate than that in low volatility group, and high volatility group had higher urea nitrogen level than that in low volatility group (all P<0.05). The amount of erythropoietin usage in the high volatility group was higher than that in moderate volatility group ( P<0.05). The Kaplan-Meier survival analysis results showed that there was no significant difference in survival rate for all-cause death (Log-rank χ2=0.735, P=0.693) and cardiovascular death (Log-rank χ2=2.961, P=0.228) in different Hb volatility groups. Cox regression analysis showed that after adjusting for age, sex, serum creatinine, and blood albumin, higher Hb volatility was associated with a lower risk of cardiovascular death ( HR=0.972, 95% CI 0.947-0.999, P=0.040). After adjusting for related confounding factors, higher Hb volatility was still a protective factor for cardiovascular death in the substandard group ( HR=0.946, 95% CI 0.903-0.992, P=0.022), but there was no significant correlation between Hb fluctuation and all-cause death. Multivariate linear regression analysis results showed that the fluctuation level of Hb was positively correlated with Kt/V ( B=4.682, 95% CI 2.480-6.884, P<0.001) and erythropoietin dosages ( B=0.001, 95% CI 0-0.001, P=0.003), and negatively correlated with baseline Hb ( B=-0.554, 95% CI -0.651--0.457, P<0.001). Conclusions:High Hb variability is a protective factor for cardiovascular death in PD patients with lower Hb level (substandard Hb). Adopting a reasonable program to correct anemia timely to reach the standard level has a greater impact on reducing risk of cardiovascular death in PD patients than Hb variation in anemia treatment.