19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.
Humans ; Medicine, Chinese Traditional/standards* ; China ; Drugs, Chinese Herbal/adverse effects* ; United States ; United States Food and Drug Administration

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

This study aimed to determine the drug resistance phenotype and genetic characteristics of Listeria monocytogenes ST5 LK100 isolated from a neonate,which provided a basis for the diagnosis and treatment of L.monocyto-genes infection and to enhance the understanding of the genomic characteristics of this strain.A suspected L.monocytogenes strain was isolated from the gastric juice sample of an infected neonate,and identified with a VITEK2 Compact automatic mi-crobial identification instrument and 16S RNA sequencing.Five drug sensitivity tests were conducted on the identified strain with the E-test method.Additionally,the whole genome of the strain was sequenced using a third-generation sequencing plat-form.The antibiotic resistance elements of the strain were identified by BlastN with the CARD antibiotic resistance gene data-base.The multilocus sequence typing(MLST),serotyping,and virulence genes of the strain was determined by Pasteur da-tabase,the virulence gene distribution was analyzed using the virulence analysis website.The prophages of the strain were predicted and annotate by PHASTER online website.The strain(LK100)isolated from the neonate was identified as L.monocytogenes.This strain was sensitive to penicillin,ampicil-lin,meropenem,erythromycin,and trimethoprim-sulfame-thoxazole antibiotics.The MLST type and serotype was ST5 and 1/2b-3b,respectively.The total length of the chromoso-mal genome of LK100 was 3 032 582 bp with a GC content of 37.91％,and it contained a complete circular plasmid with a se-quence length of 52 822 bp.The strain LK100 carried complete InlA protein,LIPI-1 pathogenicity island,SSI-1 stress survival island,and an LGI2 genomic island.The intrinsic antibiotic resistance genes were mainly located on the chromosome.Five prophage sequences were predicted in the LK100 genome.This study identified a strain of ST5 L.monocytogenes LK100 from an infected neonate and characterized its genome and antibiotic sensitivity,laying the foundation for further research on ST5 L.monocytogenes.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To analyze the clinical characteristics and all-cause mortality influencing factors of patients with Keshan disease.Methods:Clinical data of patients with Keshan disease from Keshan disease areas in Sichuan Province and Yunnan Province were collected and retrospectively analyzed for clinical characteristics and survival status during regular follow-up. According to the survival status of patients, the survey subjects were divided into a survival group and a death group. All-cause mortality (referring to the death caused by various reasons throughout the follow-up period) was used as the study endpoint. Kaplan-Meier (K-M) survival curve analysis and log-rank χ 2 test were performed, univariate and multivariate Cox regression analysis were used for all-cause mortality factor analysis. Results:A total of 176 patients with Keshan disease were collected, including 92 cases in Sichuan Province and 84 cases in Yunnan Province. Among all the patients, there were 105 males, accounting for 59.66%, and 71 females, accounting for 40.34%. The age was (53.89 ± 13.19) years old. Thirty-five cases died from all causes, with a mortality rate of 19.89%. There were significant differences in age ( t = 2.09, P = 0.038), New York Heart Association (NYHA) cardiac function grading (χ 2 = 14.62, P < 0.001) and ventricular premature contraction (χ 2 = 6.82, P = 0.009) between the survival group and the death group. K-M survival curve analysis showed that patients with Keshan disease complicated by premature ventricular contraction and high NYHA cardiac function grading (Ⅲ and Ⅳ) had higher all-cause mortality (log-rank χ 2 = 8.72, 22.49, P < 0.05). Univariate Cox regression analysis showed that NYHA cardiac function grading and ventricular premature contraction ( HR = 3.09, 2.71, P < 0.05) were predictive influencing factors for all-cause mortality in patients with Keshan disease. Multivariate Cox regression analysis showed that NYHA cardiac function grading ( HR = 6.57, P = 0.002) and ventricular premature contraction ( HR = 2.98, P = 0.050) were independent factors for all-cause mortality in patients with Keshan disease. Conclusions:Among 176 patients with Keshan disease, the number of patients with poor cardiac function (NYHA cardiac function grading Ⅲ and Ⅳ) and arrhythmia is high. NYHA cardiac function grading and ventricular premature contractions are independent influencing factors for all-cause mortality in patients with Keshan disease.

Objective:To analyze the clinical characteristics, prognosis and gene mutation in patients with dilated cardiomyopathy (DCM) in Keshan disease area of Sichuan Province, and to explore the risk factors for all-cause death in DCM patients.Methods:In June 2016, 55 DCM patients diagnosed at the local disease prevention and control center through clinical manifestations, electrocardiogram examination, and echocardiography were selected as the survey subjects in Mianning County, Liangshan Yi Autonomous Prefecture, and Renhe District, Panzhihua City, Keshan disease areas of Sichuan Province. Baseline clinical data were analyzed and long-term follow-up was conducted. The follow-up period ended June 15, 2021, with the endpoint of all-cause death. Univariate Cox regression was used to analyze the influencing factors of all-cause death in patients, and Kaplan-Meier (K-M) survival curve was used to analyze the survival time of patients. At the same time, peripheral venous blood was collected from 27 DCM patients. After separating white blood cells, DNA was extracted, and whole exome sequencing was performed to screen potential pathogenic genes.Results:Among the 55 DCM patients, 40 were males and 15 were females. The age was (54.09 ± 12.38) years old. The heart function classification of New York Heart Association (NYHA) was mainly grade Ⅱ and Ⅲ, accounting for 94.55% (52/55). The follow-up time for 55 DCM patients was (7.02 ± 2.96) years, and 17 patients experienced all-cause death, accounting for 30.91% (17/55), including 15 males and 2 females. Compared with the survival group, the death group had a lower incidence of syncope (χ 2 = 6.57, P = 0.010), but higher rates of bilateral lower limb edema (χ 2 = 6.43, P = 0.017), pulmonary congestion (χ 2 = 7.61, P = 0.006), intraventricular conduction block (χ 2 = 6.41, P = 0.011), and angiotensin-converting enzyme inhibitor (ACEI) use (χ 2 = 6.57, P = 0.010), as well as increased left ventricular diameter ( t = 2.36, P = 0.022). Univariate Cox regression analysis showed that bilateral lower limb edema [hazard ratio ( HR) = 4.61, P = 0.042] and intraventricular conduction block ( HR = 3.20, P = 0.019) were risk factors for all-cause death of DCM patients. The results of K-M survival curve analysis showed that patients with bilateral lower limb edema and intraventricular conduction block had higher all-cause death rates (log-rank χ 2 = 5.02, 6.24, P = 0.025, 0.012). Whole exome sequencing results showed that 4 patients were detected to carry pathogenic or suspected pathogenic gene mutations, with a positive rate of 14.81% (4/27), involving three genes: β-myosin heavy chain 7 (MYH7), calreticulin 3 (CALR3), and gelsolin (GSN). Conclusions:The all-cause death rate of DCM patients in the Keshan disease area of Sichuan Province is relatively high. Dead patients are prone to bilateral lower limb edema, pulmonary congestion, and intraventricular conduction block, as well as increased left ventricular diameter. Bilateral lower limb edema and intraventricular conduction block are independent predictive risk factors for all-cause death in DCM patients. MYH7, CALR3 and GSN are involved in the pathogenesis of DCM.