Effects of semaglutide on gut microbiota, cognitive function and inflammation in obese mice.

Objective: This study aims to investigate the effects of semaglutide on gut microbiota, cognitive function, and inflammation in obese mice. Method: Twenty-four C57BL/6J male mice were randomly assigned to three groups: a normal-chow diet group (NCD, n = 8), high-fat diet group (HFD, n = 8), and HFD+semaglutide group (Sema, n = 8). The mice were fed a HFD to establish an animal model of obesity and then administered with semaglutide or saline for 12 weeks. Cognitive function was assessed using the Morris water maze test. Serum pro-inflammatory cytokines were measured. 16S rRNA gene sequencing technology was used to explore gut microbiota characteristics in obese mice. Result: Obese mice showed significant cognitive impairment and inflammation. Semaglutide improved cognitive function and attenuated inflammation induced by a HFD diet. The abundance of gut microbiota was significantly changed in the HFD group, including decreased Akkermansia, Muribaculaceae, Coriobacteriaceae_UCG_002, Clostridia_UCG_014 and increased Romboutsia, Dubosiella, Enterorhabdus. Whereas semaglutide could dramatically reverse the relative abundance of these gut microbiota. Correlation analysis suggested that cognitive function was positively correlated with Muribaculaceae and Clostridia_UCG_014, and negatively associated with Romboutsia and Dubosiella. Romboutsia was positively correlated with TNFα, IL-6 and IL-1ß. While Clostridia_UCG_014 was negatively related to TNFα, IL-6 and IL-1ß. Conclusions: For the first time semaglutide displayed different regulatory effects on HFD-induced gut microbiota dysbiosis. Semaglutide could regulate the structure and composition of gut microbiota associated with cognitive function and inflammation. Thus, affecting gut microbiota might be a potential mechanism of semaglutide in attenuating cognitive function and inflammation.

Risk factors for peripherally inserted central venous catheter-related complications in children: A retrospective cohort study.

To explore the risk factors for peripherally inserted central venous catheter (PICC)-related complications in children. This retrospective study analyzed data collected from electronic medical records. A total of 584 patients with indwelling PICC treated between January 2019 and August 2021 were included in this study. According to the occurrence of PICC-related complications, the patients without PICC-related complications were included in the control group (n = 538) and those with PICC-related complications were included the observation group (n = 46). The risk factors for PICC-related complications were analyzed. Of the 584 patients with PICCs, 46 (7.88%) had PICC-related complications. Univariate analysis revealed significant differences in venipuncture (P < .001), oozing of blood from the puncture point (P < .001), indwelling time (P < .001), intravenous nutrient solution (P < .001), and catheter type (P = .003). Complications were used as dependent variables. The independent variables were vein puncture, blood oozing at the puncture point, indwelling time, intravenous nutrient solution, and catheter type. Multivariate logistic regression analysis revealed that the vein puncture (odds ratio [OR] 10.115, 95% confidence interval [CI] 5.034-20.323, P < .001), puncture point blood oozing (OR 9.217, 95% CI 3.860-22.004, P < .001), indwelling time (OR 6.390, 95% CI 3.527-10.972, P = .005), intravenous nutrient solution (OR 2.593, 95% CI 1.675-4.015, P < .001), and catheter type (OR 8.588, 95% CI 2.048-19.095, P = .013) were all risk factors for PICC-related complications in children. Venipuncture, oozing of blood from the puncture point, indwelling time, intravenous nutrient solution, and catheter type are risk factors for PICC-related complications in children. Significant attention should be paid to whether the puncture point is bleeding, the presence or absence of an intravenous nutrient solution, duration of catheterization, type of catheterization, and venipuncture. Additionally, preventive nursing measures should be implemented as soon as possible to reduce the risk of complications related to peripheral PICC.

Analysis 33 patients of non-DS-AMKL with or without acquired trisomy 21 from multiple centers and compared to 118 AML patients.

BACKGROUND: Acute megakaryoblastic leukemia (AMKL) without Down syndrome (non-DS-AMKL) usually a worse outcome than DS-AMKL. Acquired trisomy 21(+21) was one of the most common cytogenetic abnormalities in non-DS-AMKL. Knowledge of the difference in the clinical characteristics and prognosis between non-DS-AMKL with +21 and those without +21 is limited. OBJECTIVE: Verify the clinical characteristics and prognosis of non-DS-AMKL with +21. METHOD: We retrospectively analyzed 33 non-DS-AMKL pediatric patients and 118 other types of AML, along with their clinical manifestations, laboratory data, and treatment response. RESULTS: Compared with AMKL without +21, AMKL with +21 has a lower platelet count (44.04 ± 5.01G/L) at onset (P > 0.05). Differences in remission rates between AMKL and other types of AML were not significant. Acquired trisomy 8 in AMKL was negatively correlated with the long-term OS rate (P < 0.05), while +21 may not be an impact factor. Compared with the other types of AML, AMKL has a younger onset age (P < 0.05), with a mean of 22.27 months. Anemia, hemorrhage, lymph node enlargement, lower white blood cell, and complex karyotype were more common in AMKL (P < 0.05). AMKL has a longer time interval between onset to diagnosis (53.61 ± 71.15 days) (P < 0.05), and patients with a diagnosis delay ≥3 months always presented as thrombocytopenia or pancytopenia initially. CONCLUSIONS: Due to high heterogeneity, high misdiagnosis rate, and myelofibrosis, parts of AMKL may take a long time to be diagnosed, requiring repeated bone marrow punctures. Complex karyotype was common in AMKL. +21 may not be a promising indicator of a poor prognosis.

Retinal Microvascular Diameters are Associated with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the association between retinal microvascular diameters and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 690 patients with T2DM were included in this retrospective study. Patients were divided into DKD and non-DKD groups according to urine microalbumin/creatinine ratio and estimated glomerular filtration rate. Retinal microvascular diameters were measured by the automated retinal image analysis system. Multivariate logistic regression analysis and restricted cubic splines were used to assess the relationships between the retinal microvascular diameters and DKD in patients with T2DM. Results: Multivariate logistic regression showed that widened diameters of retinal venules and narrowed diameters of retinal arterioles were associated with DKD after adjusting for potential confounding variables. There was a significant linear trend between the diameters of superior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.080), inferior temporal retinal venula (P for trend < 0.001, P for non-linearity = 0.111) and central retinal venular equivalent (CRVE) (P for trend < 0.001, P for non-linearity = 0.392) and risk of DKD in patients with T2DM. The restricted cubic splines showed that narrowed retinal arteriolar diameters, superior and inferior nasal retinal venulas were associated with the risk of DKD in a non-linear fashion (all P for non-linearity < 0.001). Conclusion: Wider retinal venular diameters and narrower retinal arteriolar diameters were associated with an increased risk of DKD in patients with T2DM. Widened retinal venular diameters, especially CRVE, superior and inferior temporal retinal venula, were positively associated with an increased risk of DKD in a linear fashion. In contrast, narrowed retinal arteriolar diameters were associated with the risk of DKD in a non-linear fashion.

Influence of land use changes on landscape connectivity for North China leopard (Panthera pardus japonensis).

North China leopard (Panthera pardus japonensis) is the most widespread subspecies of leopard and one of the rare and endangered species in China. It is currently confined to several isolated natural reserves, and little is known about its habitat network connectivity with land use changes. This study was conducted to assess the impacts of land use changes on landscape connectivity for North China leopard in the Great Taihang Region. Circuit theory-based connectivity models and least-cost path analyses were used to delineate pathways suitable for species movement, and evaluate the impacts of land use changes on landscape connectivity. The results revealed that there were 37 least-cost paths in 1990 and 38 in 2020. The area of forest land increased from 57,142.74 km2 to 74,836.64 km2, with the percentage increasing from 26.61% to 34.85%. In general, the increase in forest land area promoted the landscape connectivity for North China leopard at broad spatial scales. The improvement of landscape connectivity was not always consistent with the land use changes, and there was a slightly decreasing trend on connectivity in some key movement barrier areas with high intensity of human activities. Improving landscape connectivity at broad spatial scales is as important as protecting the habitats (natural reserves) where the species lives. Our study can serve as an example of exploring the relationships between land use changes and landscape connectivity for species conservation at broad spatial scales with limited movement pattern data. This information is proved to be critical for enhancing landscape connectivity for the conservation concern of North China leopard and planning of natural reserves network.

Circ_0000745 promotes acute lymphoblastic leukemia progression through mediating miR-494-3p/NET1 axis.

BACKGROUND: Circular RNAs (circRNAs) have shown important regulatory roles in tumorigenesis. However, the role and working mechanism of circ_0000745 in acute lymphoblastic leukemia (ALL) development remain largely unclear. METHODS: The expression of circ_0000745, sperm antigen with calponin homology and coiled-coil domains 1 (SPECC1), microRNA-494-3p (miR-494-3p), and neuroepithelial cell transforming 1 (NET1) messenger RNA (mRNA) and protein was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. Flow cytometry was performed to assess cell apoptosis and cell cycle progression. Extracellular acidification rate (ECAR) was assessed to analyze cell glycolysis. Cell viability was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Ferroptosis was assessed through measuring the intracellular levels of iron and lipid reactive oxygen species (ROS). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to validate the interaction between miR-494-3p and circ_0000745 or NET1. RESULTS: Circ_0000745 expression was elevated in ALL patients and cell lines. Circ_0000745 knockdown restrained cell cycle progression and glycolysis and triggered cell apoptosis and ferroptosis. Circ_0000745 acted as a molecular sponge for miR-494-3p in ALL cells. miR-494-3p silencing partly diminished circ_0000745 knockdown-induced anti-tumor effects in ALL cells. NET1 was a target of miR-494-3p, and miR-494-3p overexpression-induced anti-tumor influences were partly counteracted by the accumulation of NET1 in ALL cells. Circ_0000745 can positively regulate NET1 expression by sponging miR-494-3p in ALL cells. CONCLUSION: Circ_0000745 contributed to ALL development partly by binding to miR-494-3p to induce NET1 expression.0020.

Spinal cord stimulation reduces cardiac pain through microglial deactivation in rats with chronic myocardial ischemia.

Angina pectoris is cardiac pain that is a common clinical symptom often resulting from myocardial ischemia. Spinal cord stimulation (SCS) is effective in treating refractory angina pectoris, but its underlying mechanisms have not been fully elucidated. The spinal dorsal horn is the first region of the central nervous system that receives nociceptive information; it is also the target of SCS. In the spinal cord, glial (astrocytes and microglia) activation is involved in the initiation and persistence of chronic pain. Thus, the present study investigated the possible cardiac pain­relieving effects of SCS on spinal dorsal horn glia in chronic myocardial ischemia (CMI). CMI was established by left anterior descending artery ligation surgery, which induced significant spontaneous/ongoing cardiac pain behaviors, as measured using the open field test in rats. SCS effectively improved such behaviors as shown by open field and conditioned place preference tests in CMI model rats. SCS suppressed CMI­induced spinal dorsal horn microglial activation, with downregulation of ionized calcium­binding adaptor protein­1 expression. Moreover, SCS inhibited CMI­induced spinal expression of phosphorylated­p38 MAPK, which was specifically colocalized with the spinal dorsal horn microglia rather than astrocytes and neurons. Furthermore, SCS could depress spinal neuroinflammation by suppressing CMI­induced IL­1ß and TNF­α release. Intrathecal administration of minocycline, a microglial inhibitor, alleviated the cardiac pain behaviors in CMI model rats. In addition, the injection of fractalkine (microglia­activating factor) partially reversed the SCS­produced analgesic effects on CMI­induced cardiac pain. These results indicated that the therapeutic mechanism of SCS on CMI may occur partially through the inhibition of spinal microglial p38 MAPK pathway activation. The present study identified a novel mechanism underlying the SCS­produced analgesic effects on chronic cardiac pain.

Predictive role of perioperative neutrophil to lymphocyte ratio in pediatric congenital heart disease associated with pulmonary arterial hypertension.

BACKGROUND: We aimed to explore the relationship between the neutrophil to lymphocyte ratio (NLR) and the early clinical outcomes in children with congenital heart disease (CHD) associated with pulmonary arterial hypertension (PAH) after cardiac surgery. METHODS: A retrospective observational study involving 190 children from January 2013 to August 2019 was conducted. Perioperative clinical and biochemical data were collected. RESULTS: We found that pre-operative NLR was significantly correlated with AST, STB, CR and UA (P < 0.05), while post-operative NLR was significantly correlated with ALT, AST, BUN (P < 0.05). Increased post-operative neutrophil count and NLR as well as decreased lymphocyte count could be observed after cardiac surgery (P < 0.05). Level of pre-operative NLR was significantly correlated with mechanical ventilation time, ICU stay time and total length of stay (P < 0.05), while level of post-operative NLR was only significantly correlated to the first two (P < 0.05). By using ROC curve analysis, relevant areas under the curve for predicting prolonged mechanical ventilation time beyond 24 h, 48 h and 72 h by NLR were statistically significant (P < 0.05). CONCLUSION: For patients with CHD-PAH, NLR was closely related to early post-operative complications and clinical outcomes, and could act as a novel marker to predict the occurrence of prolonged mechanical ventilation.

MicroRNA­802 increases hepatic oxidative stress and induces insulin resistance in high­fat fed mice.

The expression of microRNA­802 (miR­802) is known to be associated with insulin resistance (IR); however, the mechanism remains unclear. The present study investigated how miR­802 contributes to the development of IR using C57BL/6J mice fed a high­fat diet (HFD) to establish a model of IR. Adeno­associated virus overexpressing miR­802 was administered to the mice via tail vein injection. The effects of miR­802 on reactive oxygen species (ROS), lipid peroxidation (LPO) and the activities of multiple ROS­related enzymes were investigated. Western blot analysis was used to estimate the protein levels of extracellular signal regulated kinase (ERK), p38mitogen­activated protein kinases (p38MAPK), c­Jun N­terminal kinase (JNK), insulin receptor substrate 1 (IRS­1) and protein kinase B (AKT1). The results demonstrated that the levels of ROS and LPO production were increased in the livers of the miR­802­treated group compared with the control group. The activities of the ROS­related enzymes were reduced. Furthermore, the expression of phosphorylated (phosphor)­p38MAPK and phosphor­JNK were upregulated in the miR­802 overexpression group, whereas there was no difference in the expression levels of phosphor­ERK. The expression levels of phosphor­AKT1 were reduced in the miR­802­treated group and these effects were reversed by miR­802 knockdown. In conclusion, the results demonstrate that miR­802 may cause IR by activating the JNK and p38MAPK pathways to increase hepatic oxidative stress.

The clinical effect of Prednisone in combination with Mycophenolate mofetil on idiopathic thrombocytopenic purpura (ITP) and its influence on the level of peripheral blood T lymphocytes and NK lymphocytes.

OBJECTIVE: To explore he curative effect and safety of Prednisone in combination with Mycophenolate in treating ITP and its influence on the level of peripheral blood T lymphocytes and NK lymphocytes. METHOD: 93 cases of ITP patients were divided into the observation group and the control group by the Random Number Table method, 48 cases for the observation group, 45 for another. Patients in the control group orally took 0.5 mg/kg Prednisone Acetate tablets daily, two times each in the morning and evening. And the observation group, based on the treatment of the control group, orally took Mycophenolate Mofetil Dispersible tablets twice a day, 1 g each time. According to patients' conditions, 3 to 5 courses were set for treatment with 3 weeks a course. Compared PLT amount and the changing situation of inflammatory factors, CD3+ and CD3+CD95L+ before and after the treatment, the level of CD3+Caspase-3+ and CD3+Caspase-8+, NK+, NK+ CD95L+, NK+Caspase-3+, NK+Caspase-8, the curative effect and adverse events. RESULT: After treatment, PLT amount in both groups increased, and the increase in the observation group was much higher than that of the control group, the difference had statistical significance (P < 0.05). The time needed for PLT amount in the control group to reach the normal and peak values was longer than that of the observation group, whose PLT peak value was higher than another group. The difference had statistical significance (P < 0.05). After the treatment, the levels of TNF-α and IL-6 were lowered, and the value of the observation group was lower than that of another. The difference between and within the group has statistical significance. After the treatment, the level of CD3+, CD3+CD95L+ and CD3+Caspase-8+ is much higher and CD3+Caspase-3+ level lower than that before the treatment. The difference has statistical significance (P < 0.05). After the treatment, the level of NK+ and NK+ CD95L+ is higher and the level of NK+Caspase-8+ lower than that before the treatment. The difference has statistical significance (P < 0.05). After the treatment, the total effective rate 91.67% of the observation group is much higher than that 75.56% of another. The difference has statistical significance (P < 0.05). After the treatment, the incidence rate of adverse events in the control group is 11.11% (5/45), while 4.17% (2/48) in the observation group. The difference between groups has statistical significance (χ2 = 3.890, P < 0.05). CONCLUSION: The curative effect of Prednisone in combination with Mycophenolate on ITP patients is better than orally taking Prednisone tablets. Moreover, when it comes to Prednisone in combination with Mycophenolate, both the PLT amount and immunocompetence are improved without much adverse reaction, and the molecules of peripheral blood T lymphocytes and NK lymphocytes can be effectively adjusted to relieve the symptoms. So the method is trustworthy to be popularized for clinical practices.