Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective:To evaluate the effectiveness of anti-G straining maneuver (AGSM) in pilots by surface electromyography (sEMG), and to explore the relationships between characteristics of sEMG and anti-G endurance in pilots.Methods:Thirty-eight male high-performance fighter pilots who completed the human centrifuge test at the Air Force Medical Center were selected. Among them, 25 completed the 8.0 G for 10 s anti-G endurance test and 13 completed the 9.0 G for 10 s anti-G endurance test. The sEMG tester was used to keep track of the changes of sEMG in rectus abdominis, rectus femoris, anterior tibial and gastrocnemius muscles while pilots were engaged in AGSM. The anti-G endurance was evaluated according to the changes of visual fields and consciousness. The pilots were divided into 3 groups: the good vision and consciousness group, peripheral visual field narrowing group and endurance endpoint group. The differences in the integral electromyogram (iEMG), mean power frequency (MPF) and muscle input rates between the 3 groups were investigated.Results:A total of 25 pilots completed the 8.0 G for 10 s anti-G endurance test. Among them, 8 (32.0%) were in the good vision and consciousness group, 13 (52.0%) in the peripheral visual field narrowing group and 4 (16.0%) reached the endurance endpoint. Among the 13 pilots who completed the 9.0 G for 10 s anti-G endurance test, 3 (23.1%) were in the good vision and consciousness group, 6 (46.1%) in the peripheral visual field narrowing group, and 4 (30.8%) in the endurance endpoint group. The results of sEMG showed that the iEMG values of the anterior tibialis muscle in pilots under the 9.0 G for 10 s load were significantly different across endurance groups ( H=7.54, P=0.023), and that the iEMG values of the tibialis anterior muscle in the good vision and consciousness group were higher than those in the endurance endpoint group ( P=0.036). The negative slopes of MPF for the rectus abdominis, rectus femoris, anterior tibialis, and gastrocnemius muscles were higher in the good vision and consciousness group than in the other 2 groups, but the differences were not statistically significant ( P>0.05). During the 8.0 G for 10 s anti-G endurance test, there were significant differences in lower limb muscle contribution rates between the 3 groups ( F=4.19, P=0.029). The endurance endpoint group exhibited a lower contribution rate than the good vision and consciousness group ( P=0.025). During the 9.0 G for 10 s anti-G endurance test, there were significant differences in tibialis anterior muscle contribution rates between the 3 groups ( F=4.16, P=0.049). The endurance endpoint group demonstrated a lower contribution rate than the good vision and consciousness group ( P=0.049). Conclusions:The full and balanced activation of abdominal muscles and lower limb muscles, especially the effective mobilization of calf muscles, plays a pivotal role in improving pilots′ AGSM efficiency in high G environments.

Objective:To investigate the prospective association between lifestyle and the risk for all-cause mortality in middle-aged and elderly residents in China.Methods:The data from China Health and Retirement Longitudinal Study were used. Baseline information about the lifestyle were collected through questionnaire survey and physical measurements, and the mortality data were obtained through surveys conducted at 2-3 year intervals. A total of 5 436 study participants were included. A comprehensive lifestyle including smoking, alcohol consumption, sleep, BMI and physical activity was constructed, and a multivariate-adjusted Cox proportional hazards regression model was used to estimate the association between lifestyle and the risk for all-cause mortality.Results:During the follow-up of average 8.2 years, 695 deaths were recorded. The comprehensive lifestyle score was linearly associated with the risk for all-cause mortality. Compared with the study participants with comprehensive lifestyle score of 0-1, those with score of 2-5 all had lower risk for all-cause mortality, with HRs of 0.78 (95% CI: 0.62-0.98), 0.56 (95% CI: 0.44-0.72), 0.36 (95% CI:0.27-0.48), and 0.33 (95% CI: 0.21-0.52), respectively. The results of Cox proportional hazards regression model analysis of single lifestyle showed that compared with those with unhealthy lifestyles, the HRs of all-cause mortality for study participants who never smoked, had moderate alcohol consumption, had appropriate night sleep, maintained healthy body weight and kept active physical activity were 0.70 (95% CI: 0.57-0.84), 0.76 (95% CI: 0.64-0.90), 0.79 (95% CI: 0.67-0.94), 0.73 (95% CI: 0.62-0.87), and 0.68 (95% CI: 0.58-0.80), respectively. Conclusions:Keeping healthy lifestyles can significantly reduce the risk for all-cause mortality in middle-aged and elderly residents China. The higher the healthy lifestyle level, the lower the risk for all-cause mortality.

Objective:To analyze the cost-effectiveness of administering two doses of different types of human papillomavirus (HPV) vaccines to 12-year-old female adolescents.Methods:A decision tree Markov model with genital warts and cervical cancer as target diseases was established to analyze the effects, costs, and Quality Adjusted Life Years (QALY) of strategies such as no vaccination, two doses of bivalent HPV (HPV-2), two doses of quadrivalent HPV (HPV-4), and two doses of nine-valent HPV (HPV-9) in a 12-year-old female adolescent cohort in 2023 using 50% of the procurement price or self-funded vaccination price in pilot provinces. The number of avoided cases of cervical cancer and genital warts and the incremental cost-utility ratio (ICUR) were compared between different strategies.Results:Compared with non-vaccination, female adolescents who received two doses of HPV-2, HPV-4 and HPV-9 were able to avoid 55.2% of cervical cancer cases with HPV-2, 77.11% and 78.68% of genital warts with HPV-4, and 54.99% and 73.46% of cervical cancer with HPV-9, respectively. The ICUR of strategies HPV-2, HPV-4, and HPV-9 was -28 470.44 yuan/QALY, 29 328.26 yuan/QALY and 48 106.85 yuan/QALY, respectively. HPV-2 was the most economical strategy and could achieve net cost savings. Single-factor sensitivity analysis showed that the results were robust, and the most influential factors were discount rate, vaccine prices and direct medical costs for low-grade precancerous lesions. The probability sensitivity analysis showed that compared with the national gross domestic product (GDP) per capita in 2023, the probability of cost-utility of HPV-2, HPV-4 and HPV-9 compared with non-vaccination was 99.51%, 89.03% and 67.81%, respectively. Only when the price of a single dose of HPV-4 and HPV-9 vaccines was lower than 26.12% and 20.68% of the current self-funded vaccination price, respectively, could there be a net cost saving.Conclusion:In the case where HPV-2 adopts the pilot province procurement price and the multivalent vaccine adopts a 50% self-funded vaccination price, the vaccination of 12-year-old female adolescents with HPV-2, HPV-4 and HPV-9 has cost-effectiveness, and HPV-2 is the most economical strategy.

Objective:Analyze the clinicopatholocical and imaging characteristics of hepatic epithelioid hemangioendothelioma (HEHE) and the related factors of survival prognosis.Methods:Clinical data of 32 patients diagnosed with HEHE at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023 retrospectively analyzed, including 11 males and 21 females, aged (46.8±3.6) years. The clinical manifestations, pathological findings, CT and MRI features of the patients were analyzed and the living conditions of the patients were followed up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison.Results:Among the 32 patients, 17 (53.1%) had no obvious symptoms, 10 (31.3%) had abdominal pain, 6 (18.8%) had abdominal distension, and 4 (12.5%) had lost weight. Under the microscope, HEHE was composed of mucous matrix and epithelioid endothelial cells, with dense surrounding cells and relatively sparse center. Small blood vessels can be seen invading the junction with normal liver tissue. The positive rates of endothelial marker CD34 in immunohistochemically staining was 100%(32/32), the positive rates of CD31 were 100% (32/32). The positive rates of erythroblast transformation specific related gene were 100% (28/28), and the positive rates of Friend leukemia virus integration protein 1 (22/22) were 100%. CT and MRI scan showed that the lesion were mainly multiple nodules and in diffuse formality. In arterial phase, the lesion showed slight homogeneous or ring-like enhancement, while in portal phase, the lesion showed progressive enhancement. Some lesions may exhibit more specific "lollipop sign" ( n=9) and "target ring sign" ( n=15). The median overall survival time of the 32 patients was 47 months, and the cumulative 1-, 3-, and 5-year survival were 100%, 95.0% and 72.7%, respectively. The cumulative survival rate of patients with "target ring sign" ( n=15), extrahepatic organ involvement or metastasis ( n=8) and Ki-67 positive rate >5% ( n=10) were lower than those without the above characteristics (all P<0.05). Conclusion:The clinical manifestations of HEHE were not typical, and the tumor was rich in mucus matrix and epithelioid endothelial cells, expressing endothelial markers. CT and MRI scan mainly showed multiple nodules or diffused lesion, and the "lollipop sign" and "target ring sign" were helpful for diagnosis. HEHE patients with Ki-67 positivity rate >5%, "target ring sign", and extrahepatic organs involvement or metastasis had a poor prognosis.

The triple energizer is the pathway for the transportation and metabolism of qi,blood and body fluid in the body,and the xuanfu(sweat pores)is the way for the ascending,descending,exiting,and entering of qi movement in the muscular striae and the exterior.Professor Li Huilin believes that the pathogenesis of acne is usually due to the dysfunction of triple energizer and the stagnation of depressed yang-heat,which result into the abnormal opening and closing of the xuanfu and the accumulation of heat-toxin in the muscular striae.For the treatment of acne with traditional Chinese medicine,it is necessary to pay attention to the regulation of triple energizer-xuanfu.The treatment should be based on unblocking therapy,and the therapeutic principle of unblocking triple energizer and opening xuanfu should be taken into account.In clinical practice,it is necessary to identify the syndromes of upper energizer,middle energizer and lower energizer.The syndrome of the upper energizer is often due to fire-heat,which results from the wind-heat in lung meridian or the exuberance of heart fire.The upper-energizer syndrome can be treated by the therapy of relieving and clearing the pathogens with light and mild drugs,expelling fire-heat to open sweat pores,and through the modified use of Mahuang Lianqiao Chixiaodou Decoction,Ma Xing Shi Gan Decoction,or Puji Xiaodu Decoction.The syndrome of the middle energizer is usually due to the qi stagnation,which results from intense stomach-heat,damp-heat in the spleen and stomach,liver depression and qi stagnation,or spleen deficiency with dampness accumulation.The middle-energizer syndrome can be treated by the therapy of regulating qi movement to relieve stagnation and open sweat pores,and through the modified use of Qingwei san,Sanren Decoction,Huanglian Wendan Decoction,Chaihu Shugan Powder,or Heqi Powder.The syndrome of the lower energizer is often due to healthy-qi deficiency,which results from yin deficiency of liver and kidney,or deficiency-cold in lower energizer.The lower-energizer syndrome can be treated by the therapy of cultivating the vital essence and consolidating vital base,supplementing deficiency to open sweat pores,and through the modified use of Liuwei Dihuang Pills or Yanghe Decoction.

Objective To explore the medication rules of Professor Li Huilin in treating Hashimoto's thyroiditis(HT)complicated with hypothyroidism using data mining techniques based on the R language.Methods Prescription data of the patients with HT complicated with hypothyroidism treated by Professor Li Huilin in outpatient clinics from March 2023 to March 2024 were collected.A database was established using Microsoft Excel 2021,and R language was employed to analyze the frequency,efficacy,properties and flavors,and meridian tropism of the medicinals from Chinese herbal prescriptions.Additionally,correlation analysis,association rule analysis,and cluster analysis were performed on the medicines from Chinese herbal prescriptions.Results A total of 57 Chinese herbal prescriptions involving 125 medicinals with 782 medication frequencies were included.The top 10 frequently-used medicinals were Glycyrrhizae Radix et Rhizoma Praeparata cum Melle(Zhigancao),Angelicae Sinensis Radix(Danggui),Atractylodis Macrocephalae Rhizoma(Baizhu),Astragali Radix(Huangqi),Bupleuri Radix(Chaihu),Cinnamomi Ramulus(Guizhi),Leonuri Herba(Yimucao),Paeoniae Radix Alba(Baishao),Poria(Fuling),and Fici Simplicissimae Radix(Wuzhimaotao).Most of the medicinals had therapeutic action of tonifying deficiency.The analysis of properties and flavors showed that the majority of medicinals were mild or warm in nature,and sweet in flavor.The top three meridians having the tropism of medicinals were the liver,lung,and spleen meridians.Correlation analysis identified five strongly-correlated herbal combinations.Association rule mining revealed a core herbal combination consisting of seven medicinals of Zhigancao,Huangqi,Danggui,Chaihu,Codonopsis Radix(Dangshen),Baizhu,and Cyperi Rhizoma(Xiangfu).Cluster analysis of medicinals with a frequency of≥5 yielded five groups of herbal combination.Conclusion For the treatment of HT complicated with hypothyroidism,Professor Li Huilin follows the principle of addressing the root cause of the disease,and focuses on strengthening the spleen and replenishing qi.Moreover,attention is given to soothing the liver and regulating qi,harmonizing qi and blood simultaneously,and treating symptoms and root cause simultaneously.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective To investigate the effect and safety of Sintilimab combined with Endostar injection in the treatment of programmed cell death ligand-1(PD-L1)positive lung squamous cell carcinoma(LSCC)in elderly patients.Methods A total of 94 elderly patients with PD-L1 positive LSCC diagnosed and treated from November 2019 to November 2021 were selected as the research subjects,and they were divided into the observation group(n=47)and the control group(n=47)by random number table method.The observation group was treated with Sintilimab combined with Endostar injection,and the control group was treated with Sintilimab.Twenty-one days constituted one treatment cycle,and they were treated for 3 consecutive cycles.The clinical efficacy and improvement rate of Karnofsky performance status(KPS)score in the two groups were statistically analyzed,as well as the tumor markers[carcinoembryonic antigen(CEA),cancer antigen 125(CA125),cytokeratin 19 fragment(CYFRA21-1)],angiogenesis factors[endostatin,insulin-like growth factor-1(IGF-1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and platelet-derived growth factor(PDGF)],apoptosis factor[B-cell lymphoma-2 gene(Bcl-2),Bcl-2-associated X protein(Bax),Livin protein,programmed cell death 5(PDCD5)]before and after treatment.The toxic and side effects during treatment,progression-free survival(PFS)and median survival time at 2-year follow-up were compared between the two groups.Results After treatment,the objective remission rate and disease control rate of the observation group were higher than those of the control group(P<0.01);after treatment,the improvement rate of KPS score in the observation group was higher than that in the control group(P<0.01).After treatment,the levels of serum CEA,CA125,and CYFRA21-1 in both groups decreased,and which were lower in the observation group than in the control group(P<0.05,P<0.01).After treatment,the levels of endostatin increased in both groups,while IGF-1,VEGF,bFGF,and PDGF decreased;the levels of endostatin in the observation group were higher than those in the control group,while the levels of IGF-1,VEGF,bFGF,and PDGF were lower than those in the control group(P<0.05,P<0.01).After treatment,the levels of Bcl-2 and Livin decreased in both groups,while Bax and PDCD5 increased;the levels of Bcl-2 and Livin in the observation group were lower than those in the control group,while the levels of Bax and PDCD5 were higher than those in the control group(P<0.05,P<0.01).There was no significant difference in toxic and side effects between the two groups during treatment(P>0.05).The 2-year survival rate and median survival time of the observation group were higher or longer than those of the control group(P<0.05).Conclusion The treatment of PD-L1 positive LSCC in elderly patients with Sintilimab combined with Endostar injection can improve the therapeutic effect and the survival status of patients,inhibit tumor angiogenesis,induce tumor apoptosis,prolong the survival time of patients,and has good safety.