Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

BACKGROUND:Metal ions play an important role in the human body.With the progress of material synthesis and processing technology,a variety of metal ions that can be used in bone tissue engineering have been developed,such as magnesium(Mg2+),zinc(Zn2+),manganese(Mn2+),strontium(Sr2+),and copper(Cu2+). OBJECTIVE:To summarize the research progress and development direction of metal ions in bone tissue engineering. METHODS:The literature collected by CNKI,PubMed and WanFang databases from 2014 to 2022 was retrieved.The Chinese and English key words were"metal ions,bone tissue engineering,osteogenic activity,magnesium ions,zinc ions,manganese ions,strontium ions,copper ions,calcium ions,lithium ions,cobalt ions". RESULTS AND CONCLUSION:Different metal ions will be released to varying degrees after the materials are implanted into the body,which can change the tissue microenvironment,thus improving the ability of materials to form blood vessels and bones.Compared with growth factors,metal ions are easier to control the release rate,have lower cost,and can also improve the mechanical properties of implant materials.The application of metal ions in bone tissue engineering is full of prospects.Although some metal ions can already be used to treat bone defects,the mechanism of action of many metal ions in the human body is not completely clear,and the application effect is a lack of clinical experiment verification.Further exploration is needed before clinical application.

【Objective】 To investigate the viability of rapamycin-treated rapamycin-treated dendritic cells (DCs) in intervening transfusion-related acute lung injury (TRALI) after infection. 【Methods】 1)The TRALI mouse model was induced by lipopolysaccharide (LPS) combined with anti-H2Kd antibody. The mice anal temperature and the wet/dry ratio of lung, kidney, spleen and brain tissues were measured. 2) Mouse bone marrow-derived DC cells were induced in vitro and treated with rapamycin (10nM) for 24h. 3) Mice were injected with or without rapamycin or rapamycin-treated DC, then injected with LPS intraperitoneally one hour later, finally injected with anti-H2Kd antibody 24 hours later to induce the onset of TRALI. The death situation of the mice was observed and recorded. The condition of mice after the onset of TRALI was analyzed by mouse body temperature, lung wet-dry ratio, and pleural effusion weight and lung histopathological sections. 【Results】 By comparing the induction effects of anti-H2Kd antibody solutions with different concentrations and volumes, the mouse model induced by 0.1mg/kg LPS combined with 4.5 mg/kg anti-H2Kd antibody (infusion volume of 100μL) was selected as the TRALI mouse model for this study. After the onset of TRALI, the wet/dry ratio of the lungs could be significantly increased and the body temperature could be significantly reduced in the model mice. After the intervention of TRALI mice with DCs treated with rapamycin, the mortality rate was significantly reduced, and the lung tissue lesions of the mice were significantly improved, whose protection effect was better than that of the rapamycin-treated group. Compared with the TRALI incidence group, the weight of pleural effusion in the intervention group was significantly reduced (P<0.05), but there was no significant difference in lung wet/dry ratio and body temperature. 【Conclusion】 The combination of LPS and antibodies can effectively induce a stable and typical TRALI mouse model, suggesting that the presence of infectious inflammation and blood transfusion-related inflammatory substances are the decisive factor for the pathogenesis of TRALI. Meanwhile, DCs treated with rapamycin have a protective effect on post-infection transfusion-related acute lung injury, which is expected to be a potential cell therapy strategy to intervene in the exacerbation of TRALI.

Objective: To investigate the factors related to cardiac dysfunctions during the percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Methods: Patients diagnosed as NSTEACS receiving PCI from September 2007 to June 2018 were collected in the data base of medical record management system in Qingdao Eighth People′s Hospital. Patients with cardiac dysfunctions (≥ Killip Ⅱ grade) within 1 week after PCI were included into the case group, while patients with normal cardiac function (Killip Ⅰ grade) within 1 week after PCI were included into the control group. Firstly, baseline data of age, gender, histories of hypertension, histories of type 2 diabetes, histories of high cholesterol, histories of smoking, histories of drinking, histories of myocardial infarction, NSTEACS risk stratifications, the application of platelet glycoprotein (GP)Ⅱb/Ⅲa receptor antagonists, coronary artery SYNTAX scores, the dose of contrast agent during PCI, the peak cardiac troponin (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) within 24 h after admission was compared between the two groups; then, factors with statistical differences (P < 0.05) were analyzed by the multivariate logistic regression; at last, variables screening was performed through the backward method and likelihood ratio test. Results: A total of 3927 patients with NSTEACS receiving PCI were enrolled. After patients with incomplete information were eliminated, 313 patients were admitted to the case group and 2 906 patients were admitted to the controlled group. After the analysis of multivariate logistic regression and variables screening, it showed that >80 years old (OR = 1.758, 95% CI 1.129 to 2.367, P = 0.014), increased dose of contrast agent (OR = 1.083, 95% CI 1.007 to 1.274, P = 0.020), the peak cTnT>0.2 μg/L (OR = 2.102, 95% CI 1.703 to 3.104, P = 0.031) and NT-proBNP>450 ng/L (OR = 2.243, 95% CI 1.863 to 3.257, P = 0.015) after admission were the risk factors of cardiac dysfunctions. Conclusions Advanced age (>80 years old), increased dose of contrast agent during PCI, the peak cTnT>0.2 μg/L and NT-proBNP>450 ng/L within 24 h after admission could raise the risk of cardiac dysfunctions in patients with NSTEACS after PCI.

Objective:To examine the characteristics and trends regarding the 30-day coronary heart disease (CHD) readmission rates in patients discharged for acute myocardial infarction (AMI) in Beijing, during 2007-2012.Methods:Patients hospitalized for AMI in Beijing from 1 January 2007 to 31 December 2012 were identified from "The Cardiovascular Disease Surveillance System in Beijing". In total, 64 355 patients aged 25 years and over with permanent Beijing residency survived and discharged for AMI in Beijing during the above-said six years. After excluding duplicate and validation for the completeness and accuracy of the records, clinical features and 30-day CHD readmission rates for those AMI discharged patients were analyzed. Trends regarding the 30-day CHD readmission rates in patients discharged for AMI were analyzed by Poisson regression models.Results:The overall age-standardized average 30-day CHD readmission rate for AMI discharged patients was 7.7 % in patients aged 25 years and over in Beijing. During the six years under study, an increasing trend was observed on the 30-day CHD readmission rates for AMI discharged patients after adjusting the age and gender ( P<0.001). The age-standardized 30-day CHD readmission rates for AMI discharged patients increased by 21.3 % in the past six years, from 7.0 % in 2007 to 8.5 % in 2012. The increase of 30-day CHD readmission rates was noted in both men and women during the six years, whereas it appeared higher in women (8.4 %) than in men (7.4 %), after adjusting for age. Among the AMI discharged patients, the 30-day CHD readmission rates were higher in patients with non-ST-segment elevation myocardial infarction (NSTEMI) than those with ST-segment elevation myocardial infarction patients ( P<0.01), and higher in discharged patients with multiple comorbidities than those without multiple comorbidities ( P<0.01). Conclusions:An increasing trend in the 30-day CHD readmission rates for AMI discharged patients was observed during 2007-2012 among Beijing residents aged 25 years and over. It called for an urgent need in improving the secondary prevention of AMI discharged patients, particularly in women, with NSTEMI and those with multiple comorbidities. Findings from these unselected "real-world" data in Beijing may help to guide the management of AMI in the country as well as in other developing countries.

Objective:To analyze clinical features, prognosis and risk factors of bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH).Methods:Clinical data of 338 infants with BPD were collected from the neonatal intensive care unit (NICU) in Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University between January 2016 and December 2018. These infants were divided into PH group and non-PH group. The clinical features and prognosis were compared between these two groups by Chi-square test or nonparametric test. Risk factors for BPD-PH were analyzed with binary logistic regression model.Results:Among the 338 BPD infants, 314 had no PH (92.9%) and 24 had PH (7.1%), with an average gestational age of (27.1±1.8) weeks, and 206 were males and 132 females.PH infants had younger gestational age ((26.4±2.1) vs. (27.2±1.7) weeks, t=2.201, P=0.028) and lower birth weight ((798±255) vs. (1 003±240) g, t=4.030, P<0.01), compared to non-PH infants. Besides, duration of mechanical ventilation and non-invasive positive pressure ventilation were higher in PH group than that in non-PH group (14.3 (2.1, 43.7) vs. 0.5 (0, 4.7) d, Z=-4.553, P<0.01; 30.0 (22.5, 64.2) vs. 15.0 (7.0, 26.0) d, Z=-4.838, P<0.01). The proportions of maternal hypertension, small for gestational age (SGA), late onset sepsis, ventilator associated pneumonia, hemodynamically significant patent ductus arteriosus (hsPDA), patent ductus arteriosus (PDA) requiring ligation, severe BPD and severe extrauterine growth retardation (EUGR) were higher in PH group than those in non-PH group ((20.8% (5/24) vs. 6.4% (20/314), 33.3% (8/24) vs. 7.6% (24/314), 54.2% (13/24) vs. 7.3% (23/314), 25.0% (6/24) vs. 6.1% (19/314), 75.0% (18/24) vs. 39.2% (123/314), 45.8% (11/24) vs. 1.9% (6/314), 66.7% (16/24) vs. 7.3% (23/314), 75.0% (18/24) vs. 45.5% (143/314), all P<0.05). Multivariate logistic regression analysis showed that maternal hypertension ( OR=12.950, 95 %CI: 1.740-96.385), severe bronchopulmonary dysplasia ( OR=10.160, 95 %CI: 2.725-37.884), SGA ( OR=4.992, 95 %CI: 1.432-16.920), PDA requiring ligation ( OR=19.802, 95 %CI: 3.297-118.921), severe EUGR ( OR=20.316, 95 %CI: 2.221-185.853) were independent risk factors of BPD associated PH. In the 24 infants with PH, all 7 mild PH infants and 8 moderate PH infants survived, while 4 out of 9 severe PH infants died. Among the survivors, the longest duration of oxygen therapy was up to the corrected gestational age of 1 year and 2 months. Conclusions:PH is a severe complication of BPD, and associated with higher mortality and poor prognosis. Echocardiography screening and regular post-discharge follow up are recommended for BPD infants with risk factors of PH.

Objective To analysis the clinical pathway management efficiency under different DRG groups, for a basis for further optimizing clinical pathway management. Methods The retrospective analysis method was used to compare the average length of stay, sub-average costs, and drug proportions of patients with different DRGs in the same clinical pathway. Shapiro-Wilk was used to detect the normality of the samples, t test was used to analyze measurement data conformed to the normal distribution, non-parametric test was used to analyze the abnormal distribution data, and enumeration data was detected by using chi-square test. Results For patients with a clinical pathway of bronchial pneumonia, patients with severe complications and concomitant symptoms had no significant difference in mean hospitalization and sub-costs, regardless of whether they completed or entered the clinical pathway ( P >0.05). For the other two DRG patients, the difference between the average length of stay, sub-average costs, and the proportion of medications for patients who completed the clinical pathway and withdrew from or did not complete the clinical pathway was significant(P<0.05). In the severe surgical group, the length of stay and average cost for patients who completed the clinical pathway were lower than those who exited or did not enter the clinical pathway(P<0.05). Conclusions Patients with different severity of DRGs should be cautious when they are enrolled in the clinical pathway.

Objective To analyze the differences in hospitalization days and costs of patients with acute cholecystitis in different departments or diagnosis related groups ( DRGs ), and provide scientific references for clinical medical management. Methods All the medical record homepages of the patients with acute cholecystitis were selected from a tertiary hospital from January 2017 to December 2017. The hospital analysis system of DRGs was used to calculate the classification results of DRGs. The Kruskal-Wallis H test was used to analyze the differences in hospital stays and costs between different DRGs or departments. Results The average length of stay was the shortest and the hospitalization cost in the department of hepatobiliary surgery was lower than other departments among patients with surgery and non-surgical(all P<0.05); The average length of stay at the department of hepatobiliary surgery was lower than the same other DRGs groups, namely the department of digestive medicine and gastrointestinal surgery(all P<0.05). There was no significant difference in the cost of " acute biliary tract disease with complications" between the various departments(P>0.05). The average cost in the department of hepatobiliary surgery was the lowest, and the average cost of gastrointestinal surgery was the highest in two DRGs of " acute biliary disease without complications and concomitant symptoms" and " laparoscopic cholecystectomy without common bile duct exploration" ( all P < 0.05 ). Conclusions Department of hepatobiliary surgery was better than other departments in the treatment of acute cholecystitis. Medical institutions should follow the principle of special treatment to reduce interdisciplinary patients and improve the professional competitiveness of the department.

Objective To investigate the effect of 810 nm low-level laser on neuronal axonal regeneration of mice with spinal cord injury and its related mechanism.Methods In vivo experiment:20 Balb/c mice were randomly divided into the spinal cord injury group(SCI group)and the 810 nm low-level laser irradiation group(low-level laser group)after spinal cord injury according to the random number table method,with each group containing ten mice.A mice SCI model was established through clamp injury and the low-level laser group continuously irradiated the damaged area with weak 810 nm low-level laser with selected parameters(continuous wave with wave length 810 nm,power density 2 mW/cm2,spot are 4.5 cm2,irradiation time 50 minutes,energy 6000J/cm2).Then immunofluorescence staining was used to observe the M1 macrophage marker-inducible nitric oxide synthase(iNOS),the M2 macrophage marker arginase 1(Arg-1)and the universal marker F4/80 of macrophages after 14 days.Furthermore,in the in vitro experiment,standardized low-level laser-macrophage irradiation model was established.Another 20 Balb/c mice were used to obtain primary bone marrow-derived macrophages which were induced into M1 macrophages using lipopolysaccharide(LPS)and interferon-gamma(INF-γ).The M1 macrophages were randomly divided into the M1 macrophage group(M1 group)and the low-level laser therapy group(M1 + low-level laser group)equally according to the random number table method.The M1 group was not treated,and the M1 + low-level laser group was treated with low-level laser of selected parameters.RT-qPCR and ELISA were used to detect the expression of interleukin-1 receptor antagonist(IL-1RA)and interleukin-10(IL-10)in M1 macrophages 24 hours after irradiation.Western blot was used to analyze the expression of iNOS,Arg-1,differentiation antigen cluster 206(CD206),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),cyclic adenosine response element binding protein(CREB)and phosphorylated cyclic adenosine response element binding protein(p-CREB)in M1 macrophages 48 hours after irradiation.Dorsal root gangtion neurons(DRG)were cultured in two groups of macrophage conditioned medium,and the length of DRG axon growth was measured 48 h later to evaluate the effect of low-level laser on neuronal axon growth.Results In the in vivo experiment,compared with mice with spinal cord injury alone,the fluorescence intensity of F4/80+ iNOS+ in the spinal cord injury area decreased(1.00±0.08vs. 0.06±0.04)(P＜ 0.05)and the fluorescence intensity of F4/80 + Arg-1 + increased after low-level laser(1.00±0.07vs.2.15±0.12)(P＜0.01).In the in vitro experiment,compared with the M1 group,the expression of the M1 macrophage marker iNOS in the M1 + low-level laser group decreased(1.00±0.11 vs.0.08±0.01)(P＜ 0.01);the M2 macrophage marker Arg-1(1.00±0.14vs.2.44±0.16)(P＜0.01),and the expression of CD206(1.00±0.12 vs.1.83±0.05)(P＜0.01)increased.In addition,IL-1RA expression was increased in the M1 + low-level laser group compared with the M1 group(RT-qPCR:1.00±0.00vs.2.27±0.22)(P＜0.01)(ELISA:1435.58±100.48vs.2006.12±123.91(P＜0.05);IL-10 expression was also increased in the M1 +low-level laser group compared with the M1 group(RT-qPCR:1.00±0.00 vs. 3.45±0,56)(P＜0.05)(ELISA:137.13±4.20 vs.188.29±8.49)(P＜ 0,01);compared with the M1 group,the macrophage polarization pathway protein in the M1 + low-level laser group increased,AKT(1.07±0.12vs.1.74±0.04)(P＜0.01),p-AKT(1.00±0.12 vs.1.64±0.15)(P＜0.05),p-CREB(1.00±0.10vs.2.12±0.18)(P＜0.01).Compared with the M1 group,the conditioned medium of the M1 + low-level laser group significantly promoted DRG axon growth(567.66±63.59 vs.1068.95±130.14)(P＜ 0,05).Conclusions The 810 nm low-level laser irradiation can promote neuronal axon regeneration of mice with spinal cord injury,which may be related to the regulation of macrophage polarization phenotype by low-level laser through AKT/CREB pathway.

Objective To analyse the risk factors associated with spontaneous intestinal perforation (SIP) in extremely premature infants/extremely low birth weight infants. Method From January 2015 to December 2018, infants with gestational age (GA)<28 weeks or birth weight (BW)<1000 g admitted to our neonatal intensive care unit were enrolled to the retrospective nested case-control study.The clinical data of SIP infants (SIP group) and infants with the same GA but without SIP (control group) were randomly selected and compared. Multivariable Logistic regression was used to analyse the risk factors of SIP. Result A total of 409 extremely premature infants/extremely low birth weight infants were born during the study period. Among them, 25 SIP infants and 55 controls were enrolled. The incidence of SIP in infants with GA 22～25 weeks was 11.8％(16/136), which is higher than infants with GA 26～27 weeks (2.0％, 5/247) (χ2=16.057, P<0.001). The incidence of SIP in infants with BW 400～749 g was 13.0％(14/108), which is higher than infants with BW 750～999 g (3.4％, 8/236) (χ2=11.343, P=0.001). Multivariate Logistic regression analysis showed that twins (OR=4.153, 95％CI 1.392～12.384, P=0.011), umbilical veins catheterization (OR=15.942, 95％CI 1.026～247.789, P=0.048) and ibuprofen use within 3 days after birth (OR=15.387, 95％CI 1.519～155.883, P=0.021) were independent risk factors of SIP. Conclusion The smaller the GA and BW, the higher the incidence of SIP. Twins,umbilical veins catheterization and ibuprofen use early after birth may be independent risk factors of SIP.