This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

A high performance liquid chromatography (HPLC) method utilizing correction factors was established for the quantitative detection of related substances in flumazenil. Separation was achieved using an Agilent Pursuit XRs C18 column (250 mm × 4.6 mm, 5 μm) with an isocratic elution of dilute phosphoric acid, methanol, and tetrahydrofuran as the mobile phases. Correction factors calculated from a standard curve method were applied to determine the impurity content. The quantification of impurities in flumazenil was conducted using both external standard and correction factor methods, followed by validation and comparison of the two. For the identification of degradation products, a forced degradation approach was employed to prepare a flumazenil degradation solution, and the resulting impurities were confirmed by LC-MS analysis. The separation of flumazenil and its impurities was found to be efficient. The limits of quantification for impurities A, B, D, and E were established at 0.169 9, 0.314 7, 0.143 9, and 0.270 8 ng, respectively, with the limits of detection at 0.055 8, 0.096 9, 0.048 8, and 0.089 0 ng. These impurities demonstrated a strong linear relationship across the concentration ranges of 0.034 9-7.847 0, 0.038 7-8.710 7, 0.034 6-7.794 1, and 0.032 4-7.292 8 µg·mL^-1, respectively (n = 7). The method achieved average recoveries between 98.25% and 99.42%, with an RSD of less than 2.0% (n = 9), indicating high accuracy. The external standard and correction factor methods were used to determine the related substances in flumazenil, and the results of the two methods were consistent. The established HPLC method is characterized by its high accuracy, sensitivity, and repeatability, and is suitable for determining related substances in flumazenil.

With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work. This paper briefly introduces the intelligent early warning model of infectious diseases, summarizes the emerging surveillance and early warning methods of infectious diseases, and seeks the possibility of diversified surveillance and early warning in different epidemic stages and different outbreak scenarios of infectious diseases. This paper puts forward the idea of constructing a diversified method system of infectious diseases surveillance and early warning based on multi-stages and multi-scenarios and discusses the future development trend of infectious diseases surveillance and early warning, in order to provide reference for improving the construction level of infectious diseases surveillance and early warning system in China.
Humans ; Population Surveillance/methods* ; Communicable Diseases/epidemiology* ; Disease Outbreaks/prevention & control* ; Epidemics ; China/epidemiology*

With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work. This paper briefly introduces the intelligent early warning model of infectious diseases, summarizes the emerging surveillance and early warning methods of infectious diseases, and seeks the possibility of diversified surveillance and early warning in different epidemic stages and different outbreak scenarios of infectious diseases. This paper puts forward the idea of constructing a diversified method system of infectious diseases surveillance and early warning based on multi-stages and multi-scenarios and discusses the future development trend of infectious diseases surveillance and early warning, in order to provide reference for improving the construction level of infectious diseases surveillance and early warning system in China.
Humans ; Population Surveillance/methods* ; Communicable Diseases/epidemiology* ; Disease Outbreaks/prevention & control* ; Epidemics ; China/epidemiology*

Objective To measure the prevalence of mental health symptoms and identify the associated factors among college students at the beginning of coronavirus disease 2019(COVID-19)outbreak in China. Methods We carried out a multi-center cross-sectional study via snowball sampling and convenience sampling of the college students in different areas of China.The rates of self-reported depression,anxiety,and stress and post-traumatic stress disorder(PTSD)were assessed via the 21-item Depression-Anxiety-Stress Scale(DASS-21)and the 6-item Impact of Event Scale-Revised(IES-6),respectively.Covariates included sociodemographic characteristics,health-related data,and information of the social environment.Data pertaining to mental health service seeking were also collected.Multivariate Logistic regression analyses were performed to identify the risk factors. Results A total of 3641 valid questionnaires were collected from college students.At the beginning of the COVID-19 outbreak,535(14.69%)students had negative emotions,among which 402(11.04%),381(10.49%),and 171(4.90%)students had the symptoms of depression,anxiety,and stress,respectively.Meanwhile,1245(34.19%)college students had PTSD.Among the risk factors identified,male gender was associated with a lower likelihood of reporting depression symptoms(AOR=0.755,P=0.037],and medical students were at higher risk of depression and stress symptoms than liberal arts students(AOR=1.497,P=0.003;AOR=1.494,P=0.045).Family support was associated with lower risks of negative emotions and PTSD in college students(AOR=0.918,P<0.001;AOR=0.913,P<0.001;AOR=0.899,P<0.001;AOR=0.971,P=0.021). Conclusions College students were more sensitive to public health emergencies,and the incidence of negative emotions and PTSD was significantly higher than that before the outbreak of COVID-19.More attention should be paid to female college students who were more likely to develop negative emotions.We should strengthen positive and proper propaganda via mass media and help college students understand the situation and impact of COVID-19.Furthermore,we should enhance family support for college students.The government and relevant agencies need to provide appropriate mental health services to the students under similar circumstances to avoid the deterioration of their mental well-being.
COVID-19/epidemiology* ; Cross-Sectional Studies ; Female ; Health Status ; Humans ; Male ; Students/psychology* ; Universities

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective: To analyze the clinical characteristics of the neonates infected with SARS-CoV-2 during the Omicron outbreak in Shanghai 2022. Methods: In this retrospective case series study, all the 16 neonates with SARS-CoV-2 Omicron infection who were admitted to the neonatal unit in Shanghai Public Health Clinical Center from March 1^st to May 31^st, 2022 were enrolled. Their epidemiological history, clinical manifestations, nucleic acid cycle threshold (Ct) value and outcomes were analyzed. Based on maternal vaccination, they were divided into vaccinated group and unvaccinated group. Rank sum test and Chi-square test were used for the comparison between the groups. Results: Among the 16 neonates, 10 were male, and 6 were female. All the infants were full-term. The infection was confirmed at the age of 12.5 (8.0, 20.5) days. All the neonates had a history of exposure to infected family members, and thus horizontal transmission was the primary mode. Four infants were asymptomatic, 12 were symptomatic, and there were no severe or critical cases. The most common clinical manifestation was fever (11 cases), with the highest temperature of 38.1 (37.9, 38.3) ℃ and a course of 1-5 days. Other clinical manifestations included nasal obstruction (3 cases), runny nose (2 cases), cough (2 cases), poor feeding (2 cases), vomiting (1 case), and mild tachypnea (1 case). The complete blood counts of all neonates were within the normal range, and the C-reactive protein increased slightly in 1 infant. Chest imaging was performed in 2 infants, showing mild focal exudative changes. Nucleic acid turned negative (Ct value ≥35) within 7-15 days after diagnosis. All neonates fully recovered after supportive treatment, and the length of hospitalization was 13 (10, 14) days. In the telephone follow-up 2 weeks after discharge for all 16 cases, no infant showed reoccurrence of clinical manifestations or nucleic acid reactivation. Maternal vaccination was not significantly correlated with symptomatic infection or the persistence of positive nucleic acid result in neonates (all P>0.05). Conclusions: Horizontal transmission is the primary mode for neonatal SARS-CoV-2 Omicron infection. Neonatal infections are usually mild or asymptomatic, with good short-term outcomes. And their clinical manifestations and laboratory examinations are nonspecific.
Infant, Newborn ; Male ; Female ; Humans ; SARS-CoV-2 ; COVID-19 ; Retrospective Studies ; China/epidemiology* ; Fever ; Disease Outbreaks ; Nucleic Acids

Objective: To summarize the management and short-term outcomes of neonates delivered by mothers infected with SARS-CoV-2 Omicron variant. Methods: A retrospective study was performed on 158 neonates born to mothers infected with SARS-CoV-2 Omicron variant admitted to the isolation ward of Children's Hospital of Fudan University from March 15^th, 2022 to May 30^th, 2022. The postnatal infection control measures for these neonates, and their clinical characteristics and short-term outcomes were analyzed. They were divided into maternal symptomatic group and maternal asymptomatic group according to whether their mothers had SARS-CoV-2 symptoms. The clinical outcomes were compared between the 2 groups using Rank sum test and Chi-square test. Results: All neonates were under strict infection control measures at birth and after birth. Of the 158 neonates, 75 (47.5%) were male. The gestational age was (38⁺³±1⁺³) weeks and the birth weight was (3 201±463)g. Of the neonates included, ten were preterm (6.3%) and the minimum gestational age was 30⁺¹ weeks. Six neonates (3.8%) had respiratory difficulty and 4 of them were premature and required mechanical ventilation. All 158 neonates were tested negative for SARS-COV-2 nucleic acid by daily nasal swabs for the first 7 days. A total of 156 mothers (2 cases of twin pregnancy) infected with SARS-CoV-2 Omicron variant, the time from confirmed SARS-CoV-2 infection to delivery was 7 (3, 12) days. Among them, 88 cases (56.4%) showed clinical symptoms, but none needed intensive care treatment. The peripheral white blood cell count of the neonates in maternal symptomatic group was significantly higher than that in maternal symptomatic group (23.0 (18.7, 28.0) × 10⁹ vs. 19.6 (15.4, 36.6) × 10⁹/L, Z=2.44, P<0.05). Conclusions: Neonates of mothers infected with SARS-CoV-2 Omicron variant during third trimester have benign short-term outcomes, without intrauterine infection through vertical transmission. Strict infection control measures at birth and after birth can effectively protect these neonates from SARS-CoV-2 infection.
Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; COVID-19 ; Mothers ; Pregnancy Complications, Infectious/prevention & control* ; Retrospective Studies ; SARS-CoV-2

Cardiovascular System ; Heart