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.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

OBJECTIVE: To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient. METHODS: A patient sent from the Blood Transfusion Department of Shanxi Provincial People's Hospital to Blood Transfusion Technology Research Laboratory of Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient's blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient's blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)]. RESULTS: The patient's blood type was B, RhD positive. Initial screening of the patient's serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient's serum showed varying reaction intensities with red blood cells treated with different enzymes. MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c.376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient's son was found to have a heterozygous variant c.376C>T (p.Gln126Ter), and another heterozygous variant c.421C>A (p.Gln141Lys), which predicted a Jr(a+w) phenotype. Crossmatch tests confirmed the compatibility of blood from the patient's son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient's ongoing treatment, saving the patient's life. CONCLUSION Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.
Humans ; Blood Grouping and Crossmatching/methods* ; Blood Group Antigens/immunology* ; Blood Transfusion ; Male ; Isoantibodies/blood* ; Female ; Genotype

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.

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Objective To observe the effects of different epidural anesthesia regimens on pain degree and postpartum pelvic floor function of primiparas.Methods A total of 80 primiparas who underwent painless epidural anesthesia delivery in Xiangyang Hospital Affiliated to Hubei University of Traditional Chinese Medicine from September 2021 to September 2022 were selected as the research subjects.The primiparas were divided into control group(n=40)and observation group(n=40)according to the anesthesia plan.The primiparas in the control group received epidural anesthesia with ropivacaine combined with physiological saline,while the primiparas in the observation group received epidural anesthesia with ropivacaine combined with sufentanil.The rate of natural delivery,rate of cesarean section,rate of vaginal delivery and the duration of each labor of primiparas were compared between the two groups;the analgesic effect of primiparas in the two groups was evaluated by pain visual analogue scale(VAS)at 5,60 min after analgesia,full opening of the cervix and postpartum 24 hours;the asphyxia sta-tus of newborns in the two groups was evaluated by neonatal Apgar score at 1,5 min after birth;the complications of nausea and vomiting,cervical or perineal injuries,urinary retention of puerperas and neonatal asphyxia were recorded and the total inci-dence of complications was compared between the two groups.At 6-8 weeks after delivery,pelvic floor functional indicators such as fiber muscle strength,pelvic floor muscle closure contraction force,and static tension of pelvic floor muscles of postpar-tum women in the two groups were measured by biological stimulus feedback instrument.Results The natural delivery rate,vaginal delivery rate and cesarean section rate of primiparas in the control group was 72.5％(29/40),7.5％(3/40),20.0％(8/40),respectively;the natural delivery rate,vaginal delivery rate and cesarean section rate of primiparas in the observation group was 90.0％(36/40),5.0％(2/40)and 5.0％(2/40),respectively.The natural delivery rate of primiparas in the ob-servation group was significantly higher than that in the control group,and the cesarean section rate was significantly lower than that in the control group(P＜0.05);there was no significant difference in the vaginal delivery rate of primiparas between the two groups(P＞0.05).The first and second stages of labor of primiparas in the observation group were significantly shorter than those in the control group(P＜0.05),and there was no significant difference in the third stage of labor of primiparas be-tween the two groups(P＞0.05).The VAS score of primiparas in the observation group was significantly lower than that in the control group at 5,60 min after analgesia,full opening of the cervix and postpartum 24 hours(P＜0.05).There was no signifi-cant difference in the Apgar score of newborns between the two groups at 1,5 min after birth(P＞0.05).The total incidence of complications in the control group and the observation group was 42.50％(17/40)and 20.00％(8/40),respectively;the total incidence of complications in the observation group was significantly lower than that in the control group(x2=4.713,P＜0.05).The fiber muscle strength and pelvic floor muscle closure contraction force of postpartum women in the observation group were significantly higher than those in the control group,the static tension of pelvic floor muscles was significantly lower than that in the control group(P＜0.05).Conclusion Sufentanil combined with ropivacaine epidural anesthesia can improve the analgesic effect of primiparas during childbirth,reduce the cesarean section rate,shorten the labor process,and facilitate the recovery of pelvic floor function in primiparas,reduce maternal and infant complications.

Functional membrane microdomains (FMMs) that are mainly composed of scaffold proteins and polyisoprenoids play important roles in diverse cellular physiological processes in bacteria. The aim of this study was to identify the correlation between MK-7 and FMMs and then regulate the MK-7 biosynthesis through FMMs. Firstly, the relationship between FMMs and MK-7 on the cell membrane was determined by fluorescent labeling. Secondly, we demonstrated that MK-7 is a key polyisoprenoid component of FMMs by analyzing the changes in the content of MK-7 on cell membrane and the changes in the membrane order before and after destroying the integrity of FMMs. Subsequently, the subcellular localization of some key enzymes in MK-7 synthesis was explored by visual analysis, and the intracellular free pathway enzymes Fni, IspA, HepT and YuxO were localized to FMMs through FloA to achieve the compartmentalization of MK-7 synthesis pathway. Finally, a high MK-7 production strain BS3AT was successfully obtained. The production of MK-7 reached 300.3 mg/L in shake flask and 464.2 mg/L in 3 L fermenter.
Bacillus subtilis/metabolism* ; Vitamin K 2/metabolism* ; Bioreactors/microbiology* ; Membrane Microdomains/metabolism*

Objective:To explore any effects of combining virtual reality training with aromatherapy in caring for Alzheimer′s disease patients in a nursing home.Methods:Fifty nursing home residents with Alzheimer′s were divided at random into an observation group and a control group, each of 25. Both groups received routine rehabilitation, while the observation group was additionally given 45 minutes of virtual reality training combined with aromatherapy, 3 times a week for 6 months. Both groups′ cognition was then evaluated using the MMSE and an Alzheimer′s cognition assessment scale (ADAS-cog). Psycho-behavioral symptoms were quantified using the Alzheimer′s disease pathological behavior scale (BEHAVE-AD). Motor functioning was quantified using the timed up and go test (TUGT), the 30-second sit-to-stand test (30sCST), the 30-second arm curl test (30sACT) and the sit-and-reach test (CSRT). Ability in the activities of daily living (ADL) and life quality were quantified using the activity of daily living scale and of the quality of life scale for Alzheimer′s disease (QOL-AD) before and after the intervention.Results:After the intervention the average MMSE, ADAS-cog, BEHAVE-AD and ADL scores of both groups had improved significantly, with the average improvement in the observation group significantly greater than that in the control group. The TUGT, 30sCST, 30sACT and CSRT results of both groups were also significantly better, with those of the observation group again significantly superior, on average, to the control group′s results. The average QOL-AD score in the observation was significantly improved after the intervention, and was then significantly better than the control group′s average.Conclusions:Virtual reality training combined with aromatherapy can significantly improve the cognition, psycho-behavioral symptoms, activity in daily living, motor functioning and life quality of Alzheimer′s patients in a nursing home. It is worthy of promotion and application in nursing homes.

Objective:To observe any effect of virtual reality (VR) training on the cognitive functioning and functional fitness of nursing home residents with subjective cognitive decline (SCD).Methods:Fifty-six of such residents were randomly divided into an observation group and a control group, each of 28. Both groups received health education and routine care, but the observation group was additionally provided with 45 minutes of VR training three times a week for 6 months. The training included Baduanjin, magic, flying bird, supermarket shopping, gravity ball and gym episodes. Both groups′ cognition was evaluated using the subjective cognitive decline questionnaire (SCD-Q), the Montreal cognitive assessment (MoCA), the Rivermead Behavioural Memory Test (second edition) (RBMT-Ⅱ), a digit symbol substitution test (DSST), an animal fluency test (AFT) and trail-making test A-B (TMT A-B). Functional fitness was quantified using the 8-foot up-and-go test (8UGT), a 30-second arm curl test (30sACT), a 30-second chair stand test (30sCST), a back scratching test (BST), the sit-and-reach test (CSRT) and a 2-minute step test (2MST) before and after the 6-month intervention.Results:After the intervention, the average SCD-Q, MoCA, RBMT-Ⅱ, DSST, TMT-A, and TMT-B scores of the observation group were significantly better than before the intervention, and significantly better than the control group′s averages. And except for the back scratching their functional results were also significantly better, on average, than those of the control group.Conclusions:VR training can effectively improve the cognition and functional fitness of nur-sing home residents with SCD. Such training is worthy of promotion and wider application in nursing homes.

CRISPR/Cas9 has been widely used in engineering Saccharomyces cerevisiae for gene insertion, replacement and deletion due to its simplicity and high efficiency. The selectable markers of CRISPR/Cas9 systems are particularly useful for genome editing and Cas9-plasmids removing in yeast. In our previous research, GAL80 gene has been deleted by the plasmid pML104-mediated CRISPR/Cas9 system in an engineered yeast, in order to eliminate the requirement of galactose supplementation for induction. The maximum artemisinic acid production by engineered S. cerevisiae 1211-2 (740 mg/L) was comparable to that of the parental strain 1211 without galactose induction. Unfortunately, S. cerevisiae 1211-2 was inefficient in the utilization of the carbon source ethanol in the subsequent 50 L pilot fermentation experiment. The artemisinic acid yield in the engineered S. cerevisiae 1211-2 was only 20%-25% compared with that of S. cerevisiae 1211. The mutation of the selection marker URA3 was supposed to affect the growth and artemisinic acid production. A ura3 mutant was successfully restored by a recombinant plasmid pML104-KanMx4-u along with a 90 bp donor DNA, resulting in S. cerevisiae 1211-3. This mutant could grow normally in a fed-batch fermentor with mixed glucose and ethanol feeding, and the final artemisinic acid yield (> 20 g/L) was comparable to that of the parental strain S. cerevisiae 1211. In this study, an engineered yeast strain producing artemisinic acid without galactose induction was obtained. More importantly, it was the first report showing that the auxotrophic marker URA3 significantly affected artemisinic acid production in a pilot-scale fermentation with ethanol feeding, which provides a reference for the production of other natural products in yeast chassis.
Artemisinins ; Fermentation ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*