Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective:To construct talent training objectives and courses for undergraduate education of tropical medicine.Methods:Two rounds of questionnaire consultation were conducted among 15 experts by Delphi method. SPSS 26.0 software was used for statistical analysis, and the recovery rate, expert authority coefficient, mean of importance score, full score ratio, coefficient of variation and Kendall coordination coefficient were calculated respectively. Kendall's rank correlation test was used to analyze the degree of expert coordination, and the "boundary value method" was used to screen the indicators.Results:The effective recovery rates of the two rounds of consultation were all 100.00% and the expert authority coefficient was 0.815. The coordination coefficient was 0.25, 0.32, and 0.27, 0.36 respectively, and the significance test showed P<0.001. Finally, 11 talent training objectives and 7 courses for undergraduate education of tropical medicine were formed. Conclusions:The talent training objectives and courses for undergraduate education of tropical medicine are reasonable and reliable, which can provide theoretical support for tropical medicine talent training and have certain guiding value.

Humans ; Animals ; Mice ; NF-kappa B/metabolism* ; Crohn Disease/drug therapy* ; Dextran Sulfate ; Colitis/metabolism* ; Macrophages/metabolism* ; Adenosine Triphosphate/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/metabolism*

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with autism spectrum disorder (ASD) in conjunct with congenital heart disease (CHD). METHODS: A child who was hospitalized at the Third People's Hospital of Chengdu on April 13, 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). A GTX genetic analysis system was used to analyze the WES data and screen candidate variants for ASD. Candidate variant was verified by Sanger sequencing and bioinformatics analysis. Real-time fluorescent quantitative PCR (qPCR) was carried out to compare the expression of mRNA of the NSD1 gene between this child and 3 healthy controls and 5 other children with ASD. RESULTS: The patient, an 8-year-old male, has manifested with ASD, mental retardation and CHD. WES analysis revealed that he has harbored a heterozygous c.3385+2T>C variant in the NSD1 gene, which may affect the function of its protein product. Sanger sequencing showed that neither of his parent has carried the same variant. By bioinformatic analysis, the variant has not been recorded in the ESP, 1000 Genomes and ExAC databases. Analysis with Mutation Taster online software indicated it to be disease causing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. By qPCR analysis, the expression level of mRNA of the NSD1 gene in this child and 5 other children with ASD was significantly lower than that of the healthy controls (P < 0.001). CONCLUSION The c.3385+2T>C variant of the NSD1 gene can significantly reduce its expression, which may predispose to ASD. Above finding has enriched the mutational spectrum the NSD1 gene.
Male ; Child ; Humans ; Autism Spectrum Disorder/genetics* ; Heart Defects, Congenital/genetics* ; Computational Biology ; Genomics ; Mutation ; RNA, Messenger/genetics* ; Histone-Lysine N-Methyltransferase/genetics*

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective:Correct chest compression posture (CCP) is an important basis for high-quality cardiopulmonary resuscitation, but the research on CCP was still very limited. In this study, a new automatic analysis model was developed to achieve the purpose of objectification, standardization and automation of CCP monitoring.Methods:A total of 15 participants, including 11 professionals and 4 nonprofessionals, were recruited to participate in the field experiment. The video data were recorded simultaneously with zed cameras in the front and 45-degree sides. All participants performed 120 consecutive external chest compression operations on the Smartman CPR simulator. Three experts annotated the videos independently. An intelligent algorithm was used to extract human bone points for subsequent analysis and model development. The chi-square test was used to compare the rates of the professional and nonprofessional groups.Results:The results showed that problems with wrists, fingers, center of body weight and elbow bending had the highest incidence. Through 28 800 sets of standard human skeleton point coordinate data, we obtained a reasonable range of arm angles of 169.24°- 180.00° for the left arm and 168.49°-180.00° for the right arm. By the same method, the reasonable range of the center of gravity angle is 0.00°-18.46°. Based on these results, a new chest compression posture detection model based on a dual ZED camera was developed, which can accurately identify CCP errors (accuracy 91.31%; sensitivity 80.16%; specificity 93.53%).Conclusions:This study innovatively proposed an objective evaluation method for CCP. Moreover, a new chest compression posture detection model based on a dual ZED camera was developed, which can accurately identify CCP errors to achieve automation and standardization of quality control in CPR training.

Objective:To observe the drainage effects of the venous and arterial perivascular and adventitial connective tissues(PACT)on edema of lower limbs in mice model, and to provide a new understanding of the drainage for the elderly lower extremity edema.Methods:Different doses of fluorescent sodium(FluoNa)were injected into the venous and arterial perivascular connective tissues in the feet and ankles of the lower limbs to create a model of lower extremity edema in mice.Then, at the level of the femoral artery and vein sheath, a stereoscopic fluorescence microscope was used to observe and record the drainage effect of vascular PACT pathways on the edema.Results:By tracking the diffusion and flowing of FluoNa in the interstitial space of ankle and foot, we found that(1)in addition to the local diffusion at the injection site, FluoNa can also flow along the venous and arterial PACT and the interstitial spaces between the corresponding vein and artery.(2)The flowing process along the vascular adventitia included transmission along the vascular long axis, and the long axis-perpendicular diffusion into the vascular peripheral tissue.(3)When low-dose and high-dose FluoNa were administered into the venous adventitia of the lower extremities, the venous PACT imaging was observed.(4)When low-dose and high-dose FluoNa were administered into the arterial adventitia of the lower extremities, the arterial PACT imaging was observed; (5)When low-dose and high-dose of FluoNa were administered into the near the arteriovenous-accompanying blood vessels, not only the venous PACT pathway and the arterial PACT pathway are imaged, but also the interstitial space between the pathway of the accompanying vein and artery was also visualized at the same time; (6)Histological analysis showed that the tissues stained by FluoNa were the venous and arterial adventitia and perivascular connective tissues.Conclusions:The interstitial fluid in lower extremity tissue edema can not only be drained by the venous or arterial PACT pathway, but also be drained through the interstitial space between the accompanying vein and artery when a large amount of the interstitial fluid accumulates.

Interstitial fluid (ISF) flow through vascular adventitia has been discovered recently. However, its kinetic pattern was unclear. We used histological and topographical identification to observe ISF flow along venous vessels in rabbits. By magnetic resonance imaging (MRI) in live subjects, the inherent pathways of ISF flow from the ankle dermis through the legs, abdomen, and thorax were enhanced by paramagnetic contrast. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACTs) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis, which coincided with the findings by MRI. The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow. By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues, consisting of longitudinally assembled fibers. Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow: one along adventitial fibers and another one between the vascular adventitia and its covering fascia. Using nanoparticles and surfactants, a PACT pathway was found to be accessible by a nanoparticle of <100 nm and contained two parts: a transport channel and an absorptive part. The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6‒15.6 mm/s. These data revealed that a PACT pathway was a "slit-shaped" porous biomaterial, comprising a longitudinal transport channel and an absorptive part for imbibition. The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels. A hypothetical "gel pump" is proposed based on interfacial tension and interactions to regulate ISF flow. These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.

Objective:To explore an ideal method for establishing a mouse model of chronic atrophic gastritis (CAG).Methods:CAG mouse models were established with five different modeling methods ( N-methyl- N′-nitro- N-nitrosoguanide (MNNG), sodium salicylate, sodium deoxycholate, Helicobacter pylori infection, and combinations of them) in BALB/c and C57 mice. The effect of each modeling method was evaluated by histological observation of gastric mucosa, plasma biochemical parameters, inflammatory response score, and the expression of anti-inflammatory factors. Results:The results of histological observation of gastric mucosa showed that all of the 5 methods could successfully establish CAG mouse models. In BALB/c mice, compared with the healthy control group, significant features of CAG accompanied with intestinal metaplasia was found in the model group established by combination of MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate. From the results of serological detection, compared with the normal control group, the mRNA expression levels of related anti-inflammatory factors interleukin-2, interleukin-10, interleukin-13 and growth differentiation factor-15 of each model group decreased, which indicated that the mice of each CAG model group had different degrees of inflammation. The results of plasma biochemical parameters indicated that plasma gastrin of each group decreased and the ratio of pepsinogen Ⅰ and pepsinogen Ⅱ significantly dropped. The above results demonstrated that in BLAB/c mice, MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate was better than other four modeling methods. For C57 mice, it was also found that simple chemical drug mutagenesis and Helicobacter pylori replication method both could successfully establish CAG models. No matter from pathological observation, relative expression of anti-inflammatory factors and analysis of plasma biochemical parameters, the effects of combination of the two methods was better. Conclusion:The CAG mouse model established by MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate can provide a certain reference for the establishment and application of mouse model in CAG experiments in the future for pharmacological research.

Objective:To investigate the therapeutic efficacy of Ilizarov bone shortening-lengthening technique for tibial defects of bone and soft tissue without vascular injury.Methods:A retrospective analysis was made of the 28 patients who had been treated by Ilizarov bone shortening-lengthening technique at Department of Orthopaedics, Wuxi No.9 People's Hospital from January 2007 to October 2017 for tibial de-fects of bone and soft tissue without vascular injury.They were 20 males and 8 females, aged from 18 to 69 years (average, 36.4 years).By the Gustillo classification, 5 cases belonged to type Ⅱ, 6 to type ⅢA and 17 to type ⅢB.Infection was complicated in 17 cases.After debridement or epluchage, the area of skin defects ranged from 4 cm × 3 cm to 16 cm × 5 cm and the length of bone defects from 4.5 to 11.0 cm (average, 6.9 cm).The wound healing, bone healing, functionary recovery of lower extremity and complications were observed postoperatively.Bone healing and functional recovery of lower extremity were evaluated according to the grading of Association for the Study and Application of the Method of Ilizarov (ASAMI).The complications associated with Ilizarov technique were assessed according to the Paley criteria.Results:The follow-up for all the patients lasted from 12 to 45 months (average, 20.5 months).The healing time for wounds ranged from 13 to 35 days (average, 21.9 days), the healing time for lengthened bone from 6 to 12 months (average, 8.9 months), and the healing time for bone defects at the dock sites from 6 to 11 months (8.3 months).According to the ASAMI grading, the bone healing was excellent in 21 cases and good in 7, giving an excellent to good rate of 100%(28/28) while the functionary recovery of lower extremity was excellent in 10 cases, good in 15, fair in 2 and poor in one, giving an excellent to good rate of 89.3%(25/28).The incidence was 14.3%(4/28) for major complications after Ilizarov surgery, 57.1%(16/28) for minor complications, 60.7%(17/28) for overall complications, and 1.7 times for each case.Conclusion:In the treatment of tibial defects of bone and soft tissue without vascular injury, Ilizarov bone shortening-lengthening technique can deal with the difficulties in repair of soft tissue defects, characterized by simplified wound closure, fast and improved bone healing at the dock sites, reduced complications and satisfactory functionary recovery of lower extremity.