ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective To investigate the mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

Objective:To compare the clinical characteristics of patients with drug-induced liver injury (DILI) caused by Polygonum multiflorum and other drug-induced liver injuries (DILI).Methods:A retrospective cohort study was conducted. Clinical data of seventy-three cases confirmedly diagnosed with DILI caused by Polygonum multiflorum, 168 cases diagnosed with DILI caused by other traditional Chinese medicines, and 225 cases diagnosed with DILI caused by modern medicines admitted to Peking University First Hospital, the Fipth People's Hospital of Wuxi, Yantai Qishan Hospital, and Qinhuangdao Third Hospital from January 1995 to August 2019 were selected and collected as the research subjects. The Mann-Whitney U test was used for comparison of skewed distribution of continuous data between two groups. The Kruskal-Wallis rank-sum test was used for comparison between three groups. The χ2 test was used for comparing count data between groups. Results:Among the 73 cases with DILI caused by Polygonum multiflorum, 11 (15.1%) took a single herb of Polygonum multiflorum (including its powder and boiled water), 37 (50.7%) took traditional Chinese patent medicines containing Polygonum multiflorum, and 25 (34.2%) took a traditional Chinese medicine formula containing Polygonum multiflorum. The age of the DILI group caused by Polygonum multiflorum was 48 years old, which was lower than the other two groups (the DILI group caused by other traditional Chinese medicines: 55 years old, the DILI group caused by modern medicines: 52 years old; P<0.01). The levels of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase were all higher than the other two groups ( P<0.05). The proportion of patients with antinuclear antibody positivity rate and severity of liver damage grade 3 was higher in the DILI group induced by Polygonum multiflorum than those in the modern drug-induced DILI group ( P<0.05). The liver cell injury type accounted for 96.6% (57/59) in the DILI group caused by Polygonum multiflorum, which was higher than that in the modern drug-induced DILI group (69.3%, 156/225) ( P<0.001). There was no statistically significant difference ( P>0.05) in gender, age, medication duration, and various biochemical indicators between patients with DILI caused by Polygonum multiflorum monotherapy and compound preparations in terms of compatibility. The ALT level in the DILI group caused by raw Polygonum multiflorum was higher than that in the DILI group caused by processed Polygonum multiflorum [the DILI group caused by raw Polygonum multiflorum: 1 289.0(921.8, 1 851.8)U/L, the DILI group caused by processed Polygonum multiflorum: 890.0(304.0,1 320.0)U/L; P<0.05] according to the comparison of processing methods. Conclusion:The degree of DILI caused by Polygonum multiflorum is more obvious than that caused by other drugs. There was no difference in the degree of DILI caused by the single and the compound formulation. However, the liver damage caused by raw Polygonum multiflorum was more severe than that caused by processed Polygonum multiflorum.

Objective To investigate the mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective:To compare the clinical characteristics of patients with drug-induced liver injury (DILI) caused by Polygonum multiflorum and other drug-induced liver injuries (DILI).Methods:A retrospective cohort study was conducted. Clinical data of seventy-three cases confirmedly diagnosed with DILI caused by Polygonum multiflorum, 168 cases diagnosed with DILI caused by other traditional Chinese medicines, and 225 cases diagnosed with DILI caused by modern medicines admitted to Peking University First Hospital, the Fipth People's Hospital of Wuxi, Yantai Qishan Hospital, and Qinhuangdao Third Hospital from January 1995 to August 2019 were selected and collected as the research subjects. The Mann-Whitney U test was used for comparison of skewed distribution of continuous data between two groups. The Kruskal-Wallis rank-sum test was used for comparison between three groups. The χ2 test was used for comparing count data between groups. Results:Among the 73 cases with DILI caused by Polygonum multiflorum, 11 (15.1%) took a single herb of Polygonum multiflorum (including its powder and boiled water), 37 (50.7%) took traditional Chinese patent medicines containing Polygonum multiflorum, and 25 (34.2%) took a traditional Chinese medicine formula containing Polygonum multiflorum. The age of the DILI group caused by Polygonum multiflorum was 48 years old, which was lower than the other two groups (the DILI group caused by other traditional Chinese medicines: 55 years old, the DILI group caused by modern medicines: 52 years old; P<0.01). The levels of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase were all higher than the other two groups ( P<0.05). The proportion of patients with antinuclear antibody positivity rate and severity of liver damage grade 3 was higher in the DILI group induced by Polygonum multiflorum than those in the modern drug-induced DILI group ( P<0.05). The liver cell injury type accounted for 96.6% (57/59) in the DILI group caused by Polygonum multiflorum, which was higher than that in the modern drug-induced DILI group (69.3%, 156/225) ( P<0.001). There was no statistically significant difference ( P>0.05) in gender, age, medication duration, and various biochemical indicators between patients with DILI caused by Polygonum multiflorum monotherapy and compound preparations in terms of compatibility. The ALT level in the DILI group caused by raw Polygonum multiflorum was higher than that in the DILI group caused by processed Polygonum multiflorum [the DILI group caused by raw Polygonum multiflorum: 1 289.0(921.8, 1 851.8)U/L, the DILI group caused by processed Polygonum multiflorum: 890.0(304.0,1 320.0)U/L; P<0.05] according to the comparison of processing methods. Conclusion:The degree of DILI caused by Polygonum multiflorum is more obvious than that caused by other drugs. There was no difference in the degree of DILI caused by the single and the compound formulation. However, the liver damage caused by raw Polygonum multiflorum was more severe than that caused by processed Polygonum multiflorum.

Objective To establish a reference interval for the pepsinogen(PG)Ⅰ,PGⅡ and PGⅠ/PGⅡ in healthy adult subjects in Zhejiang Province.Methods The data of 45 504 healthy adult subjects were collected,and the levels of serum PGⅠ and PG Ⅱ were detected by chemiluminescence microparticle immunoassay.The reference range of PGs were determined according to the CLSI-C28-A3 file.Results The median serum PGⅠ concentration in male was 132.62μg/L,PGⅡ concentration was 8.10μg/L,and PGⅠ/PGⅡ was 15.9.For females,they were 107.44μg/L,6.96μg/L and 15.0,respectively.PGI,PGⅡ concentration and PGⅠ/PGⅡ ratio were significantly higher in males than in females(P<0.001).The levels of PGⅠ and PGⅡ increased with age(P<0.001).Serum PGⅠ reference interval for male:59.79-234.97μg/L for 19-39 years old,63.33-294.62μg/L for 40-59 years old,64.25-333.61μg/L for≥60 years old,PGⅡ reference interval:3.33-22.60μg/L for 19-39 years of age,3.79-33.89μg/L for 40-59 years of age,4.15-42.08μg/L for≥60 years of age,PGⅠ/PGⅡ reference interval:those aged 19-39 years ranged from 7.3 to 31.4,those aged 40-59 years ranged from 5.8 to 30.9,and those aged≥60 years ranged from 3.9 to 30.7.The reference intervals of female PGⅠ were 48.79-215.68μg/L,52.10-276.01μg/L,and 64.34-317.20μg/L,respectively.The reference intervals of female PgⅡwere:2.87-23.93μg/L,3.41-33.31μg/L and 3.88-39.16μg/L,respectively.The reference intervals of of female PGⅠ/PGⅡ are 6.6-28.1,5.2-27.9 and 3.6-26.2.Conclusion This study determined the reference range of serum PGs deficiency in healthy subjects of different sex and age in Zhejiang Province.

Objective: To explore the characteristics underlying Th1/Th2/Th17 expression level after entecavir (ETV) discontinuation of chronic hepatitis B (CHB) patients who were HBeAg-positive and define the role of Th1/Th2/Th17 in maintaining virological response after ETV discontinuation. Methods: We selected 112 HBeAg positive CHB patients who met the withdrawal criteria according to the guideline of prevention and treatment of chronic hepatitis B (2010 version), and we also separated them into virology sustained response (SVR) group and virological relapse (VR) group according to the recurrence in 52 weeks. We detected serum level of Th1/Th2/h17 related cytokines during 0, 12, 24 and 52 weeks follow-up to further analyze their dynamic changes and expression differences. Results: The results of the study reveals that serum levels of IFN-γ in the group of SVR were at a higher level compared with VR group during follow-up (all P<0.05). While, the serum level of IL-10 decreased in SVR group and was lower than the paired IL-10 level in VR group with significance during follow-up. In VR group, the serum level of IFN-γ decreased during the first 24 weeks after ETV withdrawal, and after then, the level rose. The serum levels of IFN-γ (Th1) in SVR patients were significantly higher than those in VR patients in the different follow-up time points after ETV discontinuation (all P<0.05). And the serum levels of IL-10 (Th2) in SVR patients were significantly lower than that in VR patients (all P<0.05). The comparison of serum levels of IL-17A (Th17) between the two groups had no significant difference (all P>0.005). Conclusions The serum level of IFN-γ in SVR group maintained a high level is conducive to maintaining virological response after ETV withdrawal and high level of IL-10 may be related to virologic relapse.

Objective:To investigate the diagnostic value of MRI and CT for the liver space-occupying lesions.Methods:The clinical data of 70 cases of patients with liver space-occupying lesions in our hospital from June 2012 to May 2016 were divided into two groups and retrospectively analyzed.35 cases underwent contrast enhanced ct scans (CT group),and others underwent dynamic contrast-enhanced MR imaging(MRI group).The pathological diagnosis,number of lesions and lesions diameter were ompared between two groups.Results:No significant difference was found in the pathological diagnosis,number of lesions(71 vs 70) and lesions diameter(2.25 ± 2.01 cm vs 2.19± 1.98 cm) between two groups(P＞0.05).As the gold standard by pathological diagnosis results,correct diagnostic rate of MRIgroup were 85.71％,which was 77.14％ CT group and lower than that of the MRI group,but no significant difference was found between two groups (P＞0.05).The incidence of adverse reactions in CT group was significantly higher than that of the MRI group (P＞0.05).Conelusion:Both CT and MRI enhancement scanning have higher diagnostic value for the liver space-occupying lesions,but MRI enhancement scanning has higher safety and tolerability.