BACKGROUND:Mitochondria are of great significance in the injury and repair of acute myocardial infarction,so it is of great clinical significance to explore the pathogenesis and progression of acute myocardial infarction based on mitochondrial genes.OBJECTIVE:To explore whether mitochondrial genes can be used as reliable biomarkers to assess the progression of acute myocardial infarction.METHODS:The acute myocardial infarction dataset was downloaded from the Gene Expression Omnibus GSE66360 and GSE12288,and the human mitochondrial gene set was obtained from the mitochondrial protein database.Differential gene analysis and weighted correlation network analysis were performed on the acute myocardial infarction dataset GSE66360,and the genes were obtained for protein-protein interaction analysis,gene ontology,and kyoto encyclopedia of genes genomes analysis.The intersection genes were intersected with human mitochondrial genes to obtain differential mitochondrial genes.Gene set enrichment analysis and immune infiltration analysis were performed on differential mitochondrial genes.Receiver operating characteristic curve analysis was performed in the external dataset GSE12288 to verify the expression characteristics of the differential mitochondrial genes.RESULTS AND CONCLUSION:(1)A total of 548 differential genes were obtained for acute myocardial infarction.Differential gene analysis and weighted gene co-expression network analysis showed that the Blue module contained the most genes(4 992).There were 116 intersecting genes,among which tumor necrosis factor,interleukin-1B,interleukin-6,Toll-like receptor 4,and interleukin-10 were the core genes.(2)Gene ontology analysis showed that the biological process mainly involved inflammatory response,positive regulation of tumor necrosis factor production,cell surface receptor signaling pathway.Cell composition mainly involved tertiary granular membrane,plasma membrane outer layer,plasma membrane,etc.Molecular function mainly involved immunoglobulin G binding,transmembrane signal receptor activity,chemokine activity,etc.Kyoto encyclopedia of genes genomes analysis showed that these genes were mainly involved in tumor necrosis factor,interleukin-17,and nuclear factor kappa-light-chain-enhancer of activated B cell pathways.(3)A total of eight differential mitochondrial genes were obtained,and four characteristic genes were screened after least absolute shrinkage and selection operator and proportional hazards model analysis,including phorbol-12-myristate-13-acetate-induced protein1,BCL2 related protein A1,solute carrier family 25 member 37,and deoxyribonucleic acid polymerase beta,and corresponded to tumor protein 53,oxidative phosphorylation,sulfur metabolism,and glycerol phospholipid metabolism pathways,respectively.(4)Receiver operating characteristic curve analysis showed that the four characteristic genes were all of diagnostic significance,and were negatively correlated with resting dendritic cells and naive B cells.(5)These results suggest that the expression characteristics of phorbol-12-myristate-13-acetate-induced protein1,BCL2 related protein A1,solute carrier family 25 member 37,and deoxyribonucleic acid polymerase beta can be used as potential biomarkers to predict mitochondrial function in acute myocardial infarction,which can further improve the accuracy of prediction of acute myocardial infarction.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Objective To explore the mechanism by which the early growth response protein 1(EGR1)/AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway improves Neuro-2a cell injury via Mendelian randomization(MR),bioinformatics and in vitro models of ischemic stroke(IS).Methods The blood proteins associated with genetic susceptibility to IS were identified based on MR analysis.Then,the GSE22255 dataset was comprehensively analyzed,including GSEA,immunoinfiltration and differential expression analysis.The transcription factors closely related to the occurrence and development of IS were identified after joint analysis with MR results,and the biological functions of key genes were further verified by in vitro experiments.Results A total of 712 proteins related to IS susceptibility were identified by MR analysis.A total of 2357 differentially expressed genes were identified from the GSE22255 dataset,and 75 intersection genes and 34 transcription factors were identified after combined analysis with MR results.In vitro experiments showed that knockdown of EGR1 expression could significantly inhibit oxygen-glucose deprivation/reperfusion(OGD/R)-induced Neuro-2a cell damage,and the mechanism might be related to the up-regulation of p-AMPK and Nrf2 protein expression.Conclusion This study integrates MR analysis,transcriptomics and in vitro experiments to reveal the potential role of 75 IS susceptibility genes and transcription factor EGR1 in the pathogenesis of IS,which provides theoretical basis for the development of therapeutic drugs for IS.

Objective To explore the mechanism by which the early growth response protein 1(EGR1)/AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway improves Neuro-2a cell injury via Mendelian randomization(MR),bioinformatics and in vitro models of ischemic stroke(IS).Methods The blood proteins associated with genetic susceptibility to IS were identified based on MR analysis.Then,the GSE22255 dataset was comprehensively analyzed,including GSEA,immunoinfiltration and differential expression analysis.The transcription factors closely related to the occurrence and development of IS were identified after joint analysis with MR results,and the biological functions of key genes were further verified by in vitro experiments.Results A total of 712 proteins related to IS susceptibility were identified by MR analysis.A total of 2357 differentially expressed genes were identified from the GSE22255 dataset,and 75 intersection genes and 34 transcription factors were identified after combined analysis with MR results.In vitro experiments showed that knockdown of EGR1 expression could significantly inhibit oxygen-glucose deprivation/reperfusion(OGD/R)-induced Neuro-2a cell damage,and the mechanism might be related to the up-regulation of p-AMPK and Nrf2 protein expression.Conclusion This study integrates MR analysis,transcriptomics and in vitro experiments to reveal the potential role of 75 IS susceptibility genes and transcription factor EGR1 in the pathogenesis of IS,which provides theoretical basis for the development of therapeutic drugs for IS.

BACKGROUND:Mitochondria are of great significance in the injury and repair of acute myocardial infarction,so it is of great clinical significance to explore the pathogenesis and progression of acute myocardial infarction based on mitochondrial genes.OBJECTIVE:To explore whether mitochondrial genes can be used as reliable biomarkers to assess the progression of acute myocardial infarction.METHODS:The acute myocardial infarction dataset was downloaded from the Gene Expression Omnibus GSE66360 and GSE12288,and the human mitochondrial gene set was obtained from the mitochondrial protein database.Differential gene analysis and weighted correlation network analysis were performed on the acute myocardial infarction dataset GSE66360,and the genes were obtained for protein-protein interaction analysis,gene ontology,and kyoto encyclopedia of genes genomes analysis.The intersection genes were intersected with human mitochondrial genes to obtain differential mitochondrial genes.Gene set enrichment analysis and immune infiltration analysis were performed on differential mitochondrial genes.Receiver operating characteristic curve analysis was performed in the external dataset GSE12288 to verify the expression characteristics of the differential mitochondrial genes.RESULTS AND CONCLUSION:(1)A total of 548 differential genes were obtained for acute myocardial infarction.Differential gene analysis and weighted gene co-expression network analysis showed that the Blue module contained the most genes(4 992).There were 116 intersecting genes,among which tumor necrosis factor,interleukin-1B,interleukin-6,Toll-like receptor 4,and interleukin-10 were the core genes.(2)Gene ontology analysis showed that the biological process mainly involved inflammatory response,positive regulation of tumor necrosis factor production,cell surface receptor signaling pathway.Cell composition mainly involved tertiary granular membrane,plasma membrane outer layer,plasma membrane,etc.Molecular function mainly involved immunoglobulin G binding,transmembrane signal receptor activity,chemokine activity,etc.Kyoto encyclopedia of genes genomes analysis showed that these genes were mainly involved in tumor necrosis factor,interleukin-17,and nuclear factor kappa-light-chain-enhancer of activated B cell pathways.(3)A total of eight differential mitochondrial genes were obtained,and four characteristic genes were screened after least absolute shrinkage and selection operator and proportional hazards model analysis,including phorbol-12-myristate-13-acetate-induced protein1,BCL2 related protein A1,solute carrier family 25 member 37,and deoxyribonucleic acid polymerase beta,and corresponded to tumor protein 53,oxidative phosphorylation,sulfur metabolism,and glycerol phospholipid metabolism pathways,respectively.(4)Receiver operating characteristic curve analysis showed that the four characteristic genes were all of diagnostic significance,and were negatively correlated with resting dendritic cells and naive B cells.(5)These results suggest that the expression characteristics of phorbol-12-myristate-13-acetate-induced protein1,BCL2 related protein A1,solute carrier family 25 member 37,and deoxyribonucleic acid polymerase beta can be used as potential biomarkers to predict mitochondrial function in acute myocardial infarction,which can further improve the accuracy of prediction of acute myocardial infarction.

Objective:To investigate the effect of visceral fat thickness before operation on the operative difficulty and postoperative complications in renal transplantation recipients.Methods:A total of 179 patients diagnosed with end-stage renal disease who underwent kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2020 to January 2022 were retrospectively included. According to the visceral fat thickness measured by CT before transplantation (distance from anterior wall of abdominal aorta to parietal peritoneum at 1 cm above umbilicus), patients were divided into two groups, with 103 patients in thin visceral fat group with visceral fat thickness ≤7.5 cm and 76 patients in thick visceral fat group with visceral fat thickness>7.5 cm. The epidemiological data before renal transplantation, operative time, intraoperative blood loss, postoperative complications, renal function after transplantation and patients′ recovery state were analyzed and compared between the two groups. Measurement data were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups. The Chi-square test was used to compare the count data. Results:The mean age and body mass index of patients in thin visceral fat group [(38.70±11.50) years and (21.28±2.93) kg/m 2] were lower than those in thick visceral fat group [(43.14±11.42) years and (24.78±3.37) kg/m 2], and the differences were statistically significant ( P< 0.05). There was no significant difference in other preoperative epidemiological data between the two groups ( P>0.05). In terms of operation difficulty, the mean operation time of thin visceral fat group was (117.16±34.33) min, which was significantly shorter than that of thick visceral fat group (137.11±20.02) min. The mean intraoperative blood loss in the thin visceral fat group was (89.12±45.95) mL, which was lower than that in the thick visceral fat group (125.39±54.88) mL, the differences were statistically significant ( P<0.001). In terms of postoperative complications, 41 patients in the thin visceral fat group had postoperative infection, incision pain and intraoperative effusion, and the incidence was 39.8% (41/103), which was significantly lower than that in the thick visceral fat group (78.9%, 60/76), the difference was statistically significant ( P<0.001); However, there was no significant difference in the incidence of Clavien-Dindo grade 3 or higher complications between the two groups ( P> 0.05). There was no significant difference in serum creatinine levels at 3, 5, 7 days and 1, 2 months after surgery among patients with different visceral fat thickness ( P> 0.05). However, the mean serum creatinine level in the thin visceral fat group was (116.06±36.45) μmol/L, which was lower than that in the thick visceral fat group (133.35±72.26) μmol/L, and the difference was statistically significant ( P=0.038). There was no significant difference in the incidence of delayed renal function recovery between the two groups ( P> 0.05). At the same time, there was no significant difference in postoperative drainage tube indwelling time and hospital stay between the two groups ( P> 0.05). Conclusions:The thicker visceral fat in end-stage renal disease patients before transplantation, the higher the incidence of general postoperative complications, but the severity of complications, patients′ recovery after transplantation and the short-term function of the transplanted kidney are not significantly related to the thickness of visceral fat in the recipients. Meanwhile, although the visceral fat thickness of the recipients in this study was correlated with serum creatinine levels at 3 months after transplantation, its correlation with long-term graft renal function and graft survival time remains to be further studied.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Objective:To invetigate the influencing factors and clinical significance of liver function damage (LFD) in patients diagnosed with Corona Virus Disease 2019 (COVID-19).Methods:The retrospective case-control study was conducted. The clinicopathological data of 51 patients with COVID-19 who were admitted to the Sino-French New City Branch of Tongji Hospital Affiliated to Huazhong University of Science and Technology by the 5th group assisting team from the First Hospital of Jilin University from February 9th to 27th in 2020 were collected. There were 27 males and 24 females, aged from 36 to 86 years, with an average age of 68 years. The treatment modality was according to the diagnostic and therapeutic guideline for COVID-19 (Trial 6th edition) issued by National Health Commission. Observation indicators: (1) clinical data of patients; (2) analysis of liver function index and treatment of LFD; (3) analysis of influencing factors for LFD. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The Logistic regression method was used for univariate analysis. Results:(1) Clinical data of patients: of the 51 patients, 21 were classified as ordinary type of COVID-19, 19 as severe type and 11 as critical type. In terms of medical history, 31 patients suffered from more than or equal to one kind of chronic disease, 20 had no history of chronic disease. Thirteen patients had the drinking history and 38 had no drinking history. Seven patients were hepatitis positive and 44 were hepatitis negative. Five patients had septic shock at admission, 5 had systemic inflammatory response syndrome (SIRS), and 41 had neither shock nor SIRS. The body mass index (BMI), time from onset to admission, temperature, heart rate, respiratory rate of the 51 patients were (24±3)kg/m 2, (13±5)days, 36.5 ℃ (range, 36.0-38.1 ℃), 82 times/minutes (range, 50-133 times/minutes), 20 times/minutes (range, 12-40 times/minutes). The white blood cell count, level of creatinine, and level of b-type natriuretic peptide within 24 hours after admission were 6.3×10 9/L [range, (2.2-21.7)×10 9/L], 75 μmol/L (range, 44-342 μmol/L), 214 ng/L (range, 5-32 407 ng/L). (2) Analysis of liver function index and treatment of LFD: the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), direct bilirubin (DBil), indirect bilirubin (IBil), activated partial thromboplastin time (APTT) and prothrombin time (PT) were 31 U/L (range, 7-421 U/L), 29 U/L (range, 15-783 U/L), 36 U/L (range, 13-936 U/L), 76 U/L (range, 41-321 U/L), 4.9 μmol/L (range, 2.6-14.3 μmol/L), 5.8 μmol/L (range, 2.6-23.9 μmol/L), 37.2 s (range, 30.9-77.1 s), 13.9 s (range, 12.5-26.7 s), respectively. The percentages of cases with abnormal ALT, AST, GGT, ALP, DBil, IBil, APTT and PT were 47.1%(24/51), 47.1%(24/51), 35.3%(18/51), 13.7%(7/51), 7.8%(4/51), 2.0%(1/51), 21.6%(11/51), and 19.6%(10/51), respectively. Of the 51 patients, LFD was detected in 10 patients classified as ordinary type, in 9 patients as severe type, and in 10 as critical type, respectively. In the 51 patients, 1 of 22 patients with normal liver function developed respiratory failure and received mechanical ventilation within 24 hours after admission, while 9 of 29 patients with abnormal liver function developed respiratory failure and received mechanical ventilation, showing a significant difference between the two groups ( χ2=5.57, P<0.05). (3) Analysis of influencing factors for LFD. Results of univariate analysis showed that clinical classification of COVID-19 as critical type was a related factor for LFD of patients ( odds ratio=10.000, 95% confidence interval: 1.050-95.231, P<0.05). Conclusions:COVID-19 patients with LFD are more susceptible to develop respiratory failure. The clinical classification of COVID-19 as critical type is a related factor for LFD of patients.

OBJECTIVE： To screen the best proportion of Astragalus membranaceus injection combined with Erigeron breviscapus injection against cerebral ischemia-reperfusion injury in rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and administration group [different A. membranaceus injection-E. breviscapus injection proportion groups， being A（0 ∶ 10）， B（2 ∶ 8）， C（4 ∶ 6）， D（6 ∶ 4）， E（8 ∶ 2）， F（10 ∶ 0）groups， set by baseline geometric proportion increasing and decreasing design]， with 8 rats in each group. Except for sham operation group， reperfusion injury model of middle cerebral artery occlusion were induced by modified suture method in rats. The each administration group was given relevant medicine intraperitoneally once immediately after inducing model， and then given again after 24 hours （medication interval between the two injections of 30 min）. Constant volume of normal saline was given to rats in sham operation group and model group. Forty-eight hours after reperfusion， Longa scoring method was used to evaluate neurological impairment of rats， and neurological impairment score was recorded. Serum content of MDA and activity of SOD were measured by colorimetry assay. TTC assay was used to detect cerebral infraction， and cerebral infarction rate was calculated. Kim’s formula was used to calculate the synergistic index （q） of rats in administration groups. RESULTS： Compared with sham operation group， neurological impairment score and serum content of MDA were increased significantly in model group， while activity of SOD was decreased significantly （P＜0.01）. The area of cerebral infarction increased significantly， and the rate of cerebral infarction increased significantly （P＜0.01）. Compared with model group， neurological impairment scores and serum contents of MDA were decreased significantly in group A， B， C， D and E； neurological impairment score of group C was significantly lower than those of group A and F； serum contents of MDA in group B， C， D and E were significantly lower than that of group F （P＜0.05 or P＜0.01）. Activities of SOD in group A， B， C， D and E were increased significantly， and group C was significantly higher than group F （P＜0.05 or P＜0.01）. The cerebral infarction area of rats in each administration group was reduced to varying degrees. The cerebral infarction rates of rats in group B， C， D and E were significantly reduced， and group C and D were significantly lower than group F， while group C was significantly lower than group A （P＜0.05 or P＜0.01）. The q values of group B， C， D and E were 0.90， 1.30， 1.00， 0.70 （neurological impairment score） and 0.79， 1.27， 0.98， 0.82 （cerebral infarction rate）. CONCLUSIONS： Different ratios of A. membranaceus injection and E. breviscapus injection have certain protective effects on cerebral ischemia-reperfusion injury model rats， can relieve their neurological deficits， alleviate their oxidative stress and reduce their cerebral infarction areas. The effect of the combination of the two drugs is better than that of single use， and the optimum ratio is 4 ∶ 6.