Viral pneumonia is an infectious disease caused by virus invading the lung parenchyma and interstitial tissue and causing lung inflammation， with the incidence rising year by year. Traditional Chinese medicine （TCM） can treat viral pneumonia in a multi-component， multi-target， and holistic manner by targeting the core pathogenesis of pneumonia caused by different respiratory viruses， demonstrating minimal side effects and significant advantages. According to the theory of healthy Qi and pathogenic Qi in TCM， the struggle between healthy Qi and pathogenic Qi and the imbalance between immunity and inflammation run through the entire process of viral pneumonia， and the immunity-inflammation status at different stages of the disease reflects different relationships between healthy Qi and pathogenic Qi. Immune dysfunction leads to the deficiency of healthy Qi， causing viral infections. The struggle between healthy Qi and pathogenic Qi causes immunity-inflammation imbalance， leading to the onset of viral pneumonia. Inflammatory damage causes persistent accumulation of phlegm and stasis， leading to the progression of viral pneumonia. The cytokine storm causes immunodepletion， leading to the excess of pathogenic Qi and diminution of healthy Qi and the deterioration of viral pneumonia. After the recovery from viral pneumonia， there is a long-term imbalance between immunity and micro-inflammation， which results in healthy Qi deficiency and pathogenic Qi lingering. Healthy Qi deficiency and pathogenic Qi excess act as common core causes of pneumonia caused by different respiratory viruses. Clinical treatment should emphasize both replenishing healthy Qi and eliminating pathogenic Qi， helping to restore the balance between healthy Qi and pathogenic Qi as well as between immunity and inflammation， thus promoting the recovery of patients from viral pneumonia. According to the TCM theory of healthy Qi and pathogenic Qi， this article summarizes the immunity-inflammation mechanisms at different stages of viral pneumonia， and explores the application of the method of replenishing healthy Qi and eliminating pathogenic Qi in viral pneumonia. The aim is to probe into the scientific connotation of the TCM theory of healthy Qi and pathogenic Qi in viral pneumonia and provide ideas for the clinical application of the method of replenishing healthy Qi and eliminating pathogenic Qi to assist in the treatment of viral pneumonia.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

The health risk posed by emerging environmental contaminants has become a public concern. Increasing evidence indicate that maternal exposure to multiple emerging environmental contaminants disrupts embryonic development. However, the underlying mechanisms of this developmental toxicity remain unclear, hindering risk assessment and prevention efforts. In this column, the developmental toxicity mechanisms of various emerging pollutants were studied by employing model animals, big data analysis, and single-cell sequencing. We hope that this column will encourage further research into the developmental toxicity mechanisms of emerging environmental contaminants and provide a scientific base for policy-making.

Emerging pollutants are a class of environmental chemicals characterized by bioaccumulation, environmental persistence, and high toxicity. Their long-term accumulation poses severe threats to the environment and human health. In recent years, single-cell RNA sequencing (scRNA-seq) technology has enabled the analysis of transcriptomes at the single-cell level, revealing cellular heterogeneity and the complexity of intercellular communication. In toxicological studies, scRNA-seq technology has been applied to identify the responses of different cell types to pollutants and to elucidate the mechanisms of pollutant action during embryonic development, providing novel perspectives on the toxicity mechanisms of emerging pollutants. This paper reviewed the classification and characteristics of single-cell sequencing technologies and their applications in investigating the developmental toxicity of emerging pollutants, including perfluorinated and polyfluorinated alkyl substances (PFAS), antibiotics, microplastics, phthalates, and bisphenols. It also discussed the limitations of current studies and proposed future research directions. Through methods such as cellular heterogeneity analysis and pseudotemporal chronological analysis, single-cell sequencing can explore and validate the specific toxicity mechanisms of emerging pollutants in embryonic development. However, challenges remain, including dataset bias, batch effects, and developmental differences between humans and model organisms. Future research should focus on optimizing data analysis methods, integrating multi-omics sequencing data, and exploring the use of human organoid models in toxicological studies. Such efforts will contribute to a more comprehensive understanding of the toxicity mechanisms and long-term health impacts of emerging pollutants, providing a theoretical basis for their stringent regulation and control.

Background Exposure to per- and polyfluoroalkyl substances (PFAS) is associated with various cancers, and recent studies suggest it may also increase the risk of retinoblastoma (RB) in newborns. However, the pathogenic mechanisms remain unclear. Objective By constructing an adverse outcome pathway (AOP) framework based on public databases to elucidate the potential mechanisms linking PFAS and RB. Methods Chemical-gene interactions and disease-gene interactions from the Comparative Toxicogenomics Database were retracted to identify key toxicological disruption pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) and a priori knowledge. The Pathview package in R was employed to predict molecular initiating events, key events, and their associated phenotypes, for further understanding the relevant gene-molecule interaction toxicity pathway network. Molecular docking techniques were utilized to validate the affinity of PFAS for these molecular initiating events. An AOP framework focused on toxicological pathways was developed using classical AOP methodologies. Results The PI3K-AKT/MAPK signaling pathway was identified as a potential toxicological pathway involved in PFAS-related RB development, based on KEGG and a priori knowledge. The activation of receptor tyrosine kinases (RTKs) served as the molecular initiating event, leading to the activation of key oncogenes such as RAS and AKT, as well as nuclear factor kappa-light chainenhancer of activated B cells (NF-κB), along with the inhibition of the tumor suppressor gene P53. In this study, 14 types of PFAS demonstrated good binding affinity with most RTKs, with chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) showing particularly favorable predicted binding. Oncogenes, including the c-kit-encoded tyrosine kinase receptor for stem cell factor, epidermal growth factor receptor, and neurotrophic tyrosine kinase receptor 1, were identified as the receptors with the best predicted binding affinity. Conclusion The PI3K-AKT/MAPK signaling pathway may serve as a potential toxicological mechanism linking PFAS to an increased risk of RB.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

Background Animal studies have shown that exposure to organophosphate esters (OPEs) disturbs the composition of gut microbiome in rodents and zebrafish. However, current associated evidence in humans is limited. Considering the importance of gut microbiome in neonatal development, we need to investigate the impact of OPEs exposure on the early development stage of neonatal microbiome. Objective To investigate the associations between umbilical OPEs exposure and the diversity and composition of gut microbiome in newborns. Methods Based on the Shanghai Maternal-Child Pairs Cohort (MCPC), 391 mother-infant pairs with comprehensive follow-up information and bio-samples were enrolled in this study. Concentrations of OPEs in neonatal cord blood were quantified using ultra performance liquid chromatography-tandem mass spectrometry. Meconium samples were collected after delivery and measured through 16S rRNA sequencing on the Illumina Miseq platform. Multiple linear regression models were used to assess the effects of OPEs exposure on the alpha diversity of meconium microbiome. Principal coordinate analysis and permutational multivariate analysis of variance based on unweighted UniFrac distance were used to compare the beta diversity differences between high and low exposure groups of OPEs. Linear discriminant analysis effect size (LEfSe) was utilized to analyze the differential gut microbiome taxa between high and low OPEs exposure groups. The functional pathways involved in the meconium microbiome were predicted based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and multivariate analysis by linear models (MaAsLin2) were conducted to explore the effects of OPEs exposure on gut microbiome pathways. Results Seven OPEs were detectable in the neonatal cord blood samples, of which four were detected higher than 50% including tributyl phosphate (TBP), tris (2-butoxyethyl) phosphate (TBEP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tris (2-chloro-1 (chloromethyl) ethyl) phosphate (TDCPP), and the median concentrations of these four congeners were as follows: 0.52 μg·L⁻¹ for TBP, 2.41 μg·L⁻¹ for TBEP, 0.13 μg·L⁻¹ for EHDPP, and 2.23 μg·L⁻¹ for TDCPP. A significant association was observed between umbilical TBEP and TDCPP exposure and alpha diversity indices in neonatal meconium microbiome. Beta diversity significantly differed across varied high and low OPEs exposure groups. The results of LEfSe analysis indicated a significant correlation between umbilical OPEs exposure and 27 genera, including Streptococcus, Corynebacterium, Neisseria, Haemophilus, and Parabacteroides. The MaAsLin2 analysis identified associations between OPEs exposure and upregulation of pathways related to linoleic acid metabolism, steroid biosynthesis, Toll and Imd signaling pathway, retinol metabolism, NOD like receptor signaling pathway, and fatty acid biosynthesis . Conclusion Umbilical OPEs exposure is associated increased alpha diversity indices, increased relative abundances of Neisseria, Streptococcus, Parabacteroides, and Corynebacterium in the gut microbiome, as well as predicted metabolic pathway alterations in linoleic acid metabolism, fatty acid biosynthesis, etc. These findings indicate that umbilical OPEs exposure may disrupt meconium microbiome equilibrium.

Objective To study the application effect of quality control circle(QCC)in reducing the dissatisfaction rate of physical examination clients in health management center.Methods To establish QCC,selected the health check-up popula-tion in our hospital in September-2019 and March-2020,through the questionnaire investigation and analysis,compare the dis-satisfaction of the clients before and after the quality control circle.Results After carrying out QCC activities,the dissatisfaction of physical examination clients was significantly lower than that before QCC,and the difference was statistically significant(P＜0.05).Conclusion The activities of QCC in the health management center can effectively improve the quality of the physical examination work and reduce the dissatisfaction of the customers in the physical examination.It is of great significance to the health management.

Objective:To explore the prognostic value of serum deoxyribonuclease 1 like 3 (Dnase1L3), C-reactive protein/albumin ratio (CAR) combined with monocyte to high-density lipoprotein cholesterol ratio (MHR) in decompensated hepatitis B cirrhosis patients.Methods:A prospective selection was conducted on 236 decompensated hepatitis B cirrhosis patients (liver disease group) admitted to the Third Hospital of Qinhuangdao from January 2020 to December 2021, and 185 healthy volunteers (control group) who underwent outpatient physical examinations. The serum levels of Dnase1L3, CAR, MHR, and liver function were detected, and Pearson analysis was conducted to investigate the correlation between Dnase1L3, CAR, MHR, and liver function. Tracking the survival status of patients after 30 days of hospitalization, the risk factors affecting 30 day mortality in decompensated hepatitis B cirrhosis patients were analyzed using a multivariate logistic regression equation. The receiver operating characteristic (ROC) curve analysis was used to assess the value of Dnase1L3, CAR, and MHR in predicting 30 day in-hospital mortality in decompensated hepatitis B cirrhosis patients.Results:The serum levels of Dnase1L3, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL), CAR, and MHR in the liver disease group were higher than those in the control group (all P<0.05). The serum levels of Dnase1L3, CAR, and MHR in the liver disease group were positively correlated with AST, ALT, and TBiL (all P<0.05). Among 236 patients, 32 died within 30 days. Model for end-stage liver disease (MELD) scores>18, high Dnase1L3, high CAR, and high MHR were risk factors for 30 day mortality in decompensated hepatitis B cirrhosis patients (all P<0.05). The combined prediction of Dnase1L3, CAR, MHR, and MELD scores for 30 day mortality in decompensated patients with hepatitis B cirrhosis showed an area under the curve of 0.904, which was higher than the predicted values of 0.719, 0.678, 0.763, and 0.742 for individual indicators. Conclusions:The serum Dnase1L3 levels, CAR, and MHR are elevated in patients with decompensated hepatitis B cirrhosis, and are associated with the degree of liver function damage and mortality within 30 days of hospitalization. They have high value in predicting the prognosis of decompensated hepatitis B cirrhosis.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.