Collaborative regulation of yeast SPT-Orm2 complex by phosphorylation and ceramide.

The homeostatic regulation of serine palmitoyltransferase (SPT) activity in yeast involves N-terminal phosphorylation of Orm proteins, while higher eukaryotes lack these phosphorylation sites. Although recent studies have indicated a conserved ceramide-mediated feedback inhibition of the SPT-ORM/ORMDL complex in higher eukaryotes, its conservation and relationship with phosphorylation regulation in yeast remain unclear. Here, we determine the structure of the yeast SPT-Orm2 complex in a dephosphomimetic state and identify an evolutionarily conserved ceramide-sensing site. Ceramide stabilizes the dephosphomimetic Orm2 in an inhibitory conformation, facilitated by an intramolecular ß-sheet between the N- and C-terminal segments of Orm2. Moreover, we find that a phosphomimetic mutant of Orm2, positioned adjacent to its intramolecular ß-sheet, destabilizes the inhibitory conformation of Orm2. Taken together, our findings suggest that both Orm dephosphorylation and ceramide binding are crucial for suppressing SPT activity in yeast. This highlights a distinctive regulatory mechanism in yeast involving the collaborative actions of phosphorylation and ceramide.

Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.

The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development.

Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex.

The serine palmitoyltransferase (SPT) complex catalyzes the first and rate-limiting step in sphingolipid biosynthesis in all eukaryotes. ORM/ORMDL proteins are negative regulators of SPT that respond to cellular sphingolipid levels. However, the molecular basis underlying ORM/ORMDL-dependent homeostatic regulation of SPT is not well understood. We determined the cryo-electron microscopy structure of Arabidopsis SPT-ORM1 complex, composed of LCB1, LCB2a, SPTssa, and ORM1, in an inhibited state. A ceramide molecule is sandwiched between ORM1 and LCB2a in the cytosolic membrane leaflet. Ceramide binding is critical for the ORM1-dependent SPT repression, and dihydroceramides and phytoceramides differentially affect this repression. A hybrid ß sheet, formed by the amino termini of ORM1 and LCB2a and induced by ceramide binding, stabilizes the amino terminus of ORM1 in an inhibitory conformation. Our findings provide mechanistic insights into sphingolipid homeostatic regulation via the binding of ceramide to the SPT-ORM/ORMDL complex that may have implications for plant-specific processes such as the hypersensitive response for microbial pathogen resistance.

Views of Pharmacists and Government Representatives Toward the Pilot Chief Pharmacist System in Chinese Hospitals: A Multicenter Exploratory Qualitative Study.

Background: In China, the pharmacy departments of most hospitals have changed their main focus from drug procurement and distribution to providing pharmaceutical care services. Various regions of China have successively implemented the pilot Chief Pharmacist System (CPS) to help improve pharmaceutical care services and rational drug use in hospitals. This study was designed to explore the perspectives of pharmacists and government officials on CPS, including the advantages and barriers to the successful implementation of CPS. Methods: A qualitative study, based on semi-structured interviews, was conducted from October 1, 2018 to March 1, 2019. The interview data were gathered from 18 pharmacy staff and government representatives working in five distinct regions of China using purposive sampling. A thematic analysis approach and NVivo version 12 Plus was utilized to code and analysis of all interviews. Results: Five broad themes were identified: the role of the chief pharmacist; their attitudes toward the CPS; the advantages and results of the CPS; the barriers toward CPS; and their suggestions toward CPS. Most of the participants believed that the chief pharmacist played a vital role in a hospital. Under CPS, the hospital pharmacy department pays more attention to prescription review, medication monitoring, and pharmaceutical consultation. However, an insufficient number of pharmacy personnel, unclear authority, and inadequate salaries were the main barriers to the implementation of the CPS. Conclusion: The attitudes of most of the participants were found to be positive toward CPS in China. The CPS can enhance the prestige of the hospital pharmacy department, improve the quality of hospital pharmaceutical care services, and promote rational drug use. Nevertheless, certain barriers highlighted in this study should be addressed promptly.

The Novel lncRNA ENST00000530525 Affects ANO1, Contributing to Blood-Brain Barrier Injury in Cultured hCMEC/D3 Cells Under OGD/R Conditions.

Ischemic stroke (IS) is a major neurological disease with high fatality and residual disability burdens. Long noncoding RNAs (lncRNAs) have been found to play an important role in IS. However, the roles and significance of most lncRNAs in IS are still unknown. This study was performed to identify differentially expressed (DE) lncRNAs using a lncRNA microarray in whole blood samples of patients suffering from acute cerebral ischemia. Bioinformatics analyses, including GO, KEGG pathway enrichment analysis, and proximity to putative stroke risk location analysis were performed. The novel lncRNA, ENST00000530525, significantly decreased after IS. Furthermore, we evaluated lncRNA ENST00000530525 expression in cultured hCMEC/D3 cells under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions using fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (RT-qPCR) analysis. To investigate the function of lncRNA ENST00000530525, its over-expression (OE) and negative control (NC) plasmids were transfected into hCMEC/D3 cells, and cell viability was detected by a cell counting kit-8 (CCK-8) assay after OGD/R. LncRNA ENST00000530525 and ANO1 expression were investigated using RT-qPCR and immunofluorescence. For blood-brain barrier (BBB) permeability, FITC-dextran transendothelial permeability assay and tight junction (TJ) protein immunofluorescence assays were performed. There were 3352 DE lncRNAs in the blood samples of acute IS patients. The validation results were consistent with the gene chip data. The GO and KEGG results showed that these lncRNAs were mainly related to oxygen and glucose metabolism, leukocyte transendothelial migration, mitophagy and cellular senescence. Among these, lncRNA ENST00000530525 was the most highly downregulated lncRNA and it was mapped within the IS-associated gene anoctamin-1 (ANO1). We further found that lncRNA ENST00000530525 was downregulated in hCMEC/D3 cells under 4 h OGD and 20 h reoxygenation (OGD4/R20) conditions. Upregulating lncRNA ENST00000530525 by plasmid transfection decreased cell viability while increasing ANO1 expression and it contributed to BBB injury in hCMEC/D3 cells after OGD4/R20. The lncRNA ENST00000530525 might play deleterious roles in post-stroke pathogenesis. These results show that some DE lncRNAs in humans participate through characteristic roles in post-stroke pathogenesis; thus, the roles and significance of some novel lncRNAs in IS warrant further study.

Access to Insulin Products in Pakistan: A National Scale Cross-Sectional Survey on Prices, Availability, and Affordability.

Background: Diabetes is among the top ten most prevalent diseases in Pakistan, and the availability of medicines to treat the disease is vital for a great percentage of the country's population. Insulin was discovered a century ago; however, its access in several parts of the globe remains an issue. This study aims to evaluate prices, availability, and affordability (access components) of insulin and five comparator medicine access in Pakistan. Methods: A nationwide cross-sectional survey was conducted to evaluate the access to insulin and some comparator medicines in eight cities of Pakistan, using a modified WHO/HAI methodology. The survey included 80 medicine outlets, i.e., 40 private pharmacies and 40 public hospitals. Data for every unique insulin product available in the Pakistani market were obtained, including five comparator medicines. Percentage availability, median unit prices (MUPs), and affordability (the number of days' wages (NDWs) required for a month's course by the lowest-paid unskilled government worker) of all products were calculated, including originator brands (OBs) and biosimilar (BS) products. Results: Of all insulin products surveyed (n = 320), 87.5% were manufactured by foreign multinational companies (MNCs). None of the insulin products had an ideal availability of 80% in any of the surveyed health facilities. In the public sector, none of the insulin products had an availability of more than 50%. In the public sector, the overall availability of human insulin was 70% (including OB and BS). While in the private sector, the overall availability of human insulin was 90% and that of analog insulin was 62.5%. The analog insulin products were 72.8% costlier than the human insulin products. The median prices of BS insulin were 25.4% lower than the OB products, indicating that almost one-fourth of the cost could be saved by switching to BS human insulin from OB human insulin. All oral anti-diabetic medicines were found to be affordable, whereas none of the insulin was affordable. The NDWs for human and analog insulin were 1.38 and 5.06. Conclusion: In Pakistan, the insulin availability falls short of the WHO's benchmark of 80%. Insulin continues to be unaffordable in both private and government sectors. To increase insulin access, the government should optimize insulin procurement at all levels, promote local production, enforce biosimilar prescribing, and provide financial subsidies for these products.

Understanding of Future Prescribers About Antimicrobial Resistance and Their Preparedness Towards Antimicrobial Stewardship Activities in Pakistan: Findings and Implications.

Background: Insufficient antimicrobial-related training for physicians during their undergraduate education could have a negative impact on their prescribing. Unlike previous studies, this study not only explored the understanding and perception of Pakistani medical students about antibiotics and resistance, but also their preparedness towards antimicrobial stewardship programs. Methods: An online cross-sectional study was undertaken with final-year medical students using a validated questionnaire from January 2021 to May 2021. Descriptive and inference statistics were applied for data analysis. Results: Of 411 students, only 6.3% had undergone antimicrobial resistance (AMR) training. 16.1% of students believed that antibiotics are effective for viral ailments. More than half of the students agreed that AMR is a major healthcare problem in Pakistan (65.9%). Most students viewed poor infection control practices (66.9%), the use of too many broad-spectrum antibiotics (68.4%) for a longer duration (62.8%) with inadequate doses (67.9%) as the causes of AMR. The student's preparation was insufficient in interpreting microbiological and pathological results (26.3%), selecting the correct antibiotics (22.1%), and awareness of the antibiotic spectrum (20.9%). The median preparedness score showed significant differences with sex (p = 0.049), age (p < 0.001), institute type (p = 0.014), and family income (p = 0.006). Conclusion: Pakistani medical students showed adequate understanding of antibiotics, but lacked preparedness for several components of ASPs, including interpretation of microbiological results and spectrum of antibiotics. More steps need to be taken to prepare medical students for AMR and stewardship initiatives adequately.

Structural insights into proteolytic activation of the human Dispatched1 transporter for Hedgehog morphogen release.

The membrane protein Dispatched (Disp), which belongs to the RND family of small molecule transporters, is essential for Hedgehog (Hh) signaling, by catalyzing the extracellular release of palmitate- and cholesterol-modified Hh ligands from producing cells. Disp function requires Furin-mediated proteolytic cleavage of its extracellular domain, but how this activates Disp remains obscure. Here, we employ cryo-electron microscopy to determine atomic structures of human Disp1 (hDisp1), before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh) ligand. These structures, together with biochemical data, reveal that proteolytic cleavage opens the extracellular domain of hDisp1, removing steric hindrance to Shh binding. Structure-guided functional experiments demonstrate the role of hDisp1-Shh interactions in ligand release. Our results clarify the mechanisms of hDisp1 activation and Shh morphogen release, and highlight how a unique proteolytic cleavage event enabled acquisition of a protein substrate by a member of a family of small molecule transporters.

Association Between the Angiotensin-Converting Enzyme I/D Polymorphism and Risk of Cerebral Small Vessel Disease: A Meta-Analysis Based on 7186 Subjects.

INTRODUCTION: Cerebral small vessel disease (CSVD) causes a quarter of all strokes and is the most common pathology underlying vascular dementia. However, the mechanism of CSVD remains unclear. Numerous studies have investigated whether the angiotensin-converting enzyme (ACE) intersection/deletion (I/D) polymorphism influences the risk of CSVD, but the results are controversial. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine the existence of genetic associations between the ACE I/D polymorphism and the risk of CSVD. All relevant studies were screened and meta-analyzed using Review Manager 5.4. RESULTS: A total of 27 studies involving 7,186 subjects were identified for the meta-analysis. The results of five genetic models showed a significantly increased risk of CSVD (allelic, OR=1.30; recessive, OR=1.41; dominant, OR=1.34; homozygous, OR=1.55 and heterozygous OR=1.22) in the overall analysis. Furthermore, in subgroup analysis, increased CSVD risks were also observed in Asian and Caucasian populations. We also found no relationship between ACE I/D and leukoaraiosis (LA) in patients with lacunar infarction (LI). CONCLUSION: The ACE I/D polymorphism was positively associated with CSVD in both populations. However, this polymorphism did not increase the risk of LA in LI patients.

Awareness and Attitudes of the Pakistani Population With Regard to Physician-Pharmaceutical Company Interaction: A Cross-Sectional Study.

Objective: To determine the awareness and attitudes of the Pakistani population regarding physician-pharmaceutical company interactions. Methods: The data were collected from primary health care clinics and pharmacy outlets located within cities of six randomly selected districts of the Punjab Province. Those individuals (age ≥18 years) who have just completed their visit to the physician and well understand Urdu language were approached. Descriptive analysis was performed for all variables by using SPSS (IBM version 26). Results: A total of 3,852 participants fully completed the study out of 4,301 (response rate 89.5%). Of those, 30.9% were female; two-thirds (66.7%) were aware of drug representatives' visits to clinics. The majority were aware of pharmaceutical company material presence (or absence) in the physicians' rooms (56.6%), company items with logos (66.8%), patient education materials (73.4%), and 60.8% thought that receiving gifts from companies was "wrong/unethical" practice for physicians, which was lower in comparison to other professions such as judges to accept gifts from lawyers (65.6%) and professional sports umpires to acknowledge gifts (64.3%). A minority said that they have lower trust on physicians for using drug company notepads or pens (16.7%), going on trips sponsored by the company (16.7%), accepting gifts <15,000 PKR (90.3 US$) (26.7%), and accepting gifts >15,000 PKR (90.3 US$) (40.0%). Conclusion: Survey participants were well aware of physician-pharmaceutical company interactions. Participants were more knowledgeable regarding the pharmaceutical company presence (or absence) in physicians' offices than about gift-related practices of physicians. Trust on the physician was not affected by small gifts but by the large gifts.

Antibiotics (Macrolides and Lincosamides) Consumption Trends and Patterns in China's Healthcare Institutes. Based on a 3 Year Procurement Records, 2015-2017.

In this study, we investigated the trends and patterns of antibiotic consumption (macrolides and lincosamides) in China's healthcare institutions from 2015 to 2017. The China Drug Supply Information Platform (CDSIP) was officially launched in 2015. We collected records from this national centralized bidding procurement system between 2015 and 2017. The use of J01F antibiotics (macrolides or lincosamides) was calculated in a defined daily dose per 1000 inhabitants per day (DID).Purchase data from 70,366 national medical facilities included in the CDSIP were collected. The procurement data of 66,007 medical facilities have not changed over 3 years. There is a slight decline in the consumption of J01F antibiotics, which decreased from 3.03 DID in 2015 to 2.91 DID in 2017. Azithromycin (20.6%) was the most commonly used antibiotic in 2017 among all classes, followed by clindamycin (17.9%) and erythromycin (13.7%). Parenteral antibiotics accounted for 32.0% of total antibiotic consumption and 59.6% of total antibiotics expenditure in 2017. The overall consumption of most antibiotics decreased slightly over the 3-yearstudy period. This may be owing to China's health-related policies in the past few years. A gap still exists in antibiotic use between regions and dosage forms. Further studies are needed to optimize antibiotic prescribing and reduce antibiotic resistance.

Analysis of Antibiotic Use Patterns and Trends Based on Procurement Data of Healthcare Institutions in Shaanxi Province, Western China, 2015-2018.

Overuse of antibiotics has caused a series of global problems, especially in the underdeveloped western regions where healthcare systems are fragile. We used antibiotic procurement data of all healthcare institutions to analyze the total amount, patterns and trends of antibiotic use in Shaanxi Province, western China between 2015 and 2018. Antibiotic utilization was quantified using the standard Anatomical Therapeutic Chemical (ATC)/Defined daily dose (DDD) methodology. The World Health Organization's "Access, Watch and Reserve" (AWaRe) classification and European Surveillance of Antimicrobial Consumption (ESAC) drug-specific quality indicators were also adopted to evaluate the appropriateness and quality of antibiotic utilization. Overall, antibiotic consumption decreased from 11.20 DID in 2015 to 10.13 DID (DDDs per 1000 inhabitants per day) in 2016, then increased to 12.99 DID in 2018. The top three antibiotic categories consumed in 2018 were J01C (penicillins) 33.58%, J01D (cephalosporins) 29.76%, and J01F (macrolides) 19.14%. Parenteral antibiotics accounted for 27.41% of the total consumption. The largest proportion of antibiotic use was observed in primary healthcare institutions in rural areas, which accounts for 51.67% of total use. Consumption of the Access group, the Watch group, the Reserve group of antibiotics was 40.31%, 42.28% and 0.11%, respectively. Concurrently, the consumption of J01D and the percentage of J01 (DD + DE) (third and fourth generation cephalosporins) were at a poor level according to the evaluation of ESAC quality indicators. The total antibiotic consumption in Shaanxi Province had been on an upward trend, and the patterns of antibiotic use were not justified enough to conclude that it was rational. This is partly because there was high preference for the third and fourth generation cephalosporins and for the Watch group antibiotics.

Ferrous-activated sodium percarbonate pre-oxidation for membrane fouling control during ultrafiltration of algae-laden water.

Membrane technology has been shown to be promising for the treatment of algae-laden water, but membrane fouling is still an obstacle influencing the purification efficiency and effluent quality. To mitigate ultrafiltration membrane fouling during Microcystis aeruginosa-laden water treatment, a strategy of sodium percarbonate pre-oxidation activated with ferrous ion (Fe2+/SPC) was put forward in this study. Due to the synergistic effect of Fe2+ and SPC, this process was significantly more efficient with the terminal specific flux increased from 0.097 to 0.397, and the reversible fouling resistance reduced by approximately 80%. It was also found that subsequent sedimentation followed by Fe2+/SPC could further improve the fouling control efficiency. The model fitting results indicated that Fe2+/SPC pre-oxidation delayed the transition from standard blocking to cake filtration. Extracellular organic matter and algal cells were extracted from algal foulants to explore the contribution of each component, and the fouling control efficiencies were systematically studied. The characteristics of the algal foulants were determined with fluorescence excitation-emission matrix spectrum, and the results suggested that macromolecular proteinaceous substances were more efficiently removed by Fe2+/SPC, in comparison with humic-like matters. The alleviation of membrane fouling was also verified by the characterization methods of scanning electron microscopy and attenuated total reflection-Fourier infrared spectroscopy. Overall, the proposed strategy of Fe2+/SPC has an application prospect for membrane fouling control in algal-laden water treatment.

Effect of peroxymonosulfate oxidation activated by powdered activated carbon for mitigating ultrafiltration membrane fouling caused by different natural organic matter fractions.

Powdered activated carbon (PAC) adsorption has been widely applied prior to ultrafiltration membrane for potable water production. However, the impact of PAC adsorption on membrane fouling was still controversial. To solve this problem, combined PAC and peroxymonosulfate (PMS) pretreatment was proposed in this study. The application of PAC/PMS for mitigating membrane fouling by natural organic matter (NOM) has been evaluated, and compared with PMS oxidation or PAC adsorption alone. The influence of NOM fractions on the control efficiency was also investigated using humic acid (HA), bovine serum albumin (BSA), sodium alginate (SA), and their mixture (HA-BSA-SA). The performance was examined through normalized flux decline, fouling resistances analysis, scanning electron microscopy, and model fits. The results indicated that PAC and PMS exhibited a remarkable synergistic effect in the reduction of NOM, with the DOC reduction rates of 53.6%, 24.3%, 27.1% and 31.4% for HA, BSA, SA and HA-BSA-SA, respectively. PAC adsorption exhibited limited influence on mitigating membrane fouling, and the co-existence of PAC and HA even exacerbated fouling due to the synergistic fouling effect between them. By contrast, PAC/PMS pretreatment efficiently reduced both reversible and irreversible fouling resistances. The control efficiency was closely associated with the NOM fractions in the feed water, and followed the order of SA > HA-BSA-SA > BSA > HA. The fouling mitigation by PAC/PMS was attributed to both PAC adsorption and oxidation with SO4- and OH. The experimental results are expected to provide a feasible strategy of PAC/PMS for fouling mitigation, and simultaneously solve the problem faced by PAC adsorption.

Effect of Tai Chi Synergy T1 Exercise on Autonomic Function, Metabolism, and Physical Fitness of Healthy Individuals.

OBJECTIVES: Tai Chi synergy T1 exercise is an aerobic exercise derived mainly from Tai Chi exercise. It is also derived from the Eight Trigrams Palms, form and will boxing, mantis boxing, Qigong, and Yoga, with a total of 16 sessions in 63 minutes. In this study, we investigated its effects on autonomic modulation, metabolism, immunity, and physical function in healthy practitioners. METHOD: We recruited a total of 26 volunteers and 23 control participants. Heart rate variability (HRV), blood pressure, and body mass index (BMI) were recorded before and after practicing Tai Chi synergy T1 exercise and regular walking for 10 weeks, respectively. Serum glucose, cholesterol, and peripheral blood including B and T cell counts were also measured. They underwent one-minute bent-knee sit-ups, sit and reach test, and three-minute gradual step test. RESULTS: Tai Chi synergy T1 exercise enhanced parasympathetic modulation and attenuated sympathetic nerve control with increased very low frequency (VLF) and high frequency (HF) but decreased low frequency (LF) compared to the control group. Metabolic profiles including serum glucose, cholesterol, and BMI significantly improved after exercise. The exercise enhanced innate and adaptive immunity by increasing the counts of CD3+ T cells, CD19+ B cells, and CD16+CD56+ NK cells but decreasing the CD3+ cytotoxic T cell count. All monitored parameters including physical fitness and physical strength improved after the exercise. CONCLUSION: Tai Chi synergy T1 exercise improves autonomic modulation, body metabolism, physical fitness, and physical strength after 10 weeks of practice.

Effect of Yiqihuoxue prescription on myocardial energy metabolism after myocardial infarction via cross talk of liver kinase B1-dependent Notch1 and adenosine 5'-monophosphate-activated protein kinase.

OBJECTIVE: To investigate the effect of Yiqihuoxue prescription (YQHX) from Traditional Chinese Medicine (TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver kinase B1 (LKB1)-dependent Notch1 and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). YQHX was prepared with substances with properties that benefit, to activate blood circulation based on the TCM theory. METHODS: Animal models of myocardial infarction were established by ligating Sprague Dawley rats' left anterior descending coronary arteries. The animals were randomly divided into a myocardial infarction (MI) group, a YQHX group, a perindopril group, a r-secretase inhibitor, Notch signal inhibitor (DAPT) group, a DAPT+YQHX group and a sham group. The related drugs were administered on the second day after operation, and changes in the relevant indexes were examined on weeks 1 and 4. Changes in cardiac structure and function were examined by echocardiography. The glucose and free fatty acids (FFA) were examined by ELISA. The expression of Notch, LKB1 and AMPK mRNA was examined by a real-time fluorescence quantitative method. The expression of glucose transporter 4 (GLUT4), and the expression of total acetyl-CoA carboxylase (ACC) and its phosphorylation were examined by western blotting. RESULTS: Compared with the sham group, the expression of Notch, LKB1 and AMPK mRNA in the MI group was lower. Compared with the MI group, the expression of these mRNAs in the YQHX and perindopril groups was higher, and their expression in the DAPT group was lower. At all time points, the protein expression of GLUT4 and pACC decreased in the MI group. On week 1, the expression of pACC protein was higher. In the DAPT group, the expression of pACC protein decreased. Compared with the YQHX group, the expression of pACC protein in the DAPT + YQHX group was lower. On week 4, compared with the MI group, the expression of GLUT4 protein in the YQHX group and the perindopril group was higher. The expression of GLUT4 protein in the DAPT group decreased. Compared with the YQHX group, the expression of GLUT4 protein in the DAPT+YQHX group was lower. There was no significant difference in the expression of ACC protein between the groups. CONCLUSION: YQHX promoted cross talk between the LKB1-dependent Notch1 and AMPK in myocardial tissue after myocardial infarction. Furthermore, it regulated the glucose and lipid metabolism of cardiomyocytes at different time points, thereby ameliorating the cardiac energy metabolism via different mechanisms and protecting the heart.