ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Background::The ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) predicts cardiovascular disease (CVD) endpoints, yet its prognostic validity in high-risk populations and for type 2 diabetes mellitus (T2DM)-related adverse events remains unestablished.Methods::This study included 32,609 people aged 35-75 years in Fujian Province, China, who were at high risk for CVD. The primary endpoint was all-cause mortality during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the HDL-C/LDL-C ratio and the endpoints.Result::On the basis of the restricted RCS curve, the participants were classified as having a low (< 0.3), middle (0.3-0.5), or high (> 0.5) HDL-C/LDL-C ratio. Multivariate Cox regression analyses revealed that the risk of all-cause mortality (HR = 1.48, 95% CI 1.14-1.93, p < 0.01 for low; HR = 1.30, 95% CI 1.06-1.58, p < 0.05 for high) was increased in the low and high groups. Participants without T2DM who were at high risk for CVD had similar prognoses (HR = 1.65, 95% CI 1.19-2.28, p < 0.01 for low; HR = 1.35, 95% CI 1.05-1.74, p < 0.01 for high). However, this association was not found in participants with T2DM who were at high risk for CVD. Conclusion::HDL-C/LDL-C can be used to predict the prognosis of individuals at high risk for CVD, and maintaining HDL-C/LDL-C ratios between 0.3 and 0.5 may be the most helpful range for this population. Furthermore, maintaining this ratio range holds clinical significance for cohorts without T2DM, although further exploration is needed in this T2DM cohort.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

Background::The ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) predicts cardiovascular disease (CVD) endpoints, yet its prognostic validity in high-risk populations and for type 2 diabetes mellitus (T2DM)-related adverse events remains unestablished.Methods::This study included 32,609 people aged 35-75 years in Fujian Province, China, who were at high risk for CVD. The primary endpoint was all-cause mortality during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the HDL-C/LDL-C ratio and the endpoints.Result::On the basis of the restricted RCS curve, the participants were classified as having a low (< 0.3), middle (0.3-0.5), or high (> 0.5) HDL-C/LDL-C ratio. Multivariate Cox regression analyses revealed that the risk of all-cause mortality (HR = 1.48, 95% CI 1.14-1.93, p < 0.01 for low; HR = 1.30, 95% CI 1.06-1.58, p < 0.05 for high) was increased in the low and high groups. Participants without T2DM who were at high risk for CVD had similar prognoses (HR = 1.65, 95% CI 1.19-2.28, p < 0.01 for low; HR = 1.35, 95% CI 1.05-1.74, p < 0.01 for high). However, this association was not found in participants with T2DM who were at high risk for CVD. Conclusion::HDL-C/LDL-C can be used to predict the prognosis of individuals at high risk for CVD, and maintaining HDL-C/LDL-C ratios between 0.3 and 0.5 may be the most helpful range for this population. Furthermore, maintaining this ratio range holds clinical significance for cohorts without T2DM, although further exploration is needed in this T2DM cohort.

Objective:To investigate the heterogeneity of peripheral blood neutrophils in sepsis and provide reference for the diagnosis of sepsis.Methods:Twenty-four male C57BL/6 mice were divided into two groups, control and sepsis groups, with 12 mice in each group using a completely randomized design. The mice in the control group were injected with 100 μl saline through the tail vein, while the mice in the sepsis group were injected with an equal amount of Escherichia coli solution (3.33 McFarland turbidity standards) through the tail vein to establish the sepsis model. Peripheral blood samples were collected, and the proportions of neutrophils expressing different surface markers were detected using mass cytometry. GO and KEGG analyses were performed on neutrophil subsets with high CD62L expression, and public datasets were used for verification. The protein-protein interaction networks of CD62L were investigated to assess the value of neutrophil heterogeneity in the diagnosis of sepsis. Results:There were significant differences in the expression of markers in peripheral blood samples between the sepsis group and the control group. CD62L + neutrophil subsets were found in mice with sepsis. GO and KEGG analyses showed that CD62L + neutrophil subsets were associated with multiple biological processes and signaling pathways such as cell adhesion, migration, surface receptor activation, and immune regulation. Clinical results confirmed the correlation of neutrophil CD62L expression with the severity and prognosis of sepsis. The number of subpopulations expressing CD62L in peripheral blood neutrophils in the sepsis group was higher than that in the control group, but the expression level of CD62L in single cells in the sepsis group was significantly lower than that in the control group ( P<0.01). Protein-protein interaction network analysis showed strong interaction between CD62L and multiple important proteins such as P-selectin, P-selectin ligand, E-selectin, and vascular cell adhesion molecule-1. Conclusion:There is heterogeneity in the surface markers of neutrophils between sepsis mice and control mice, which may be a potential indicator for the diagnosis of sepsis.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

Objective:To investigate the heterogeneity of peripheral blood neutrophils in sepsis and provide reference for the diagnosis of sepsis.Methods:Twenty-four male C57BL/6 mice were divided into two groups, control and sepsis groups, with 12 mice in each group using a completely randomized design. The mice in the control group were injected with 100 μl saline through the tail vein, while the mice in the sepsis group were injected with an equal amount of Escherichia coli solution (3.33 McFarland turbidity standards) through the tail vein to establish the sepsis model. Peripheral blood samples were collected, and the proportions of neutrophils expressing different surface markers were detected using mass cytometry. GO and KEGG analyses were performed on neutrophil subsets with high CD62L expression, and public datasets were used for verification. The protein-protein interaction networks of CD62L were investigated to assess the value of neutrophil heterogeneity in the diagnosis of sepsis. Results:There were significant differences in the expression of markers in peripheral blood samples between the sepsis group and the control group. CD62L + neutrophil subsets were found in mice with sepsis. GO and KEGG analyses showed that CD62L + neutrophil subsets were associated with multiple biological processes and signaling pathways such as cell adhesion, migration, surface receptor activation, and immune regulation. Clinical results confirmed the correlation of neutrophil CD62L expression with the severity and prognosis of sepsis. The number of subpopulations expressing CD62L in peripheral blood neutrophils in the sepsis group was higher than that in the control group, but the expression level of CD62L in single cells in the sepsis group was significantly lower than that in the control group ( P<0.01). Protein-protein interaction network analysis showed strong interaction between CD62L and multiple important proteins such as P-selectin, P-selectin ligand, E-selectin, and vascular cell adhesion molecule-1. Conclusion:There is heterogeneity in the surface markers of neutrophils between sepsis mice and control mice, which may be a potential indicator for the diagnosis of sepsis.

This study， anchored in the traditional Chinese medicine （TCM） syndrome differentiation and treatment principles alongside the clinical characteristics of sepsis in Western medicine， extensively gathers and meticulously dissects the latest research findings on sepsis animal models from both Chinese and international sources. Adhering strictly to TCM syndrome diagnostic criteria for sepsis， the study conducts a thorough evaluation of various animal models across multiple dimensions， including clinical manifestations， pathological changes， and biomarker expressions， so as to reflect the degree of resemblance these models have to human sepsis TCM syndromes. The results reveal that the colon stent implantation model exhibits a higher degree of congruence with both TCM and Western medicine standards， particularly aligning with the diagnosis of the "Fu-Qi obstruction syndrome". Conversely， the extraperitoneal sepsis model shows a higher degree of congruence with TCM， fitting more closely with the diagnosis of "acute deficiency syndrome" and emphasizing the core pathogenesis of Qi deficiency in sepsis. These findings not only augment the diversity of sepsis animal models but also highlight the necessity and potential of integrated TCM and western medicine research. Current sepsis animal models predominantly focus on western pathophysiological mechanisms， with limited direct incorporation of TCM syndrome differentiation elements. This underscores the need， in future study designs， to actively explore integrating TCM syndrome classification and intervention principles into model development. This could be achieved by manipulating model-inducing factors and observing more TCM-specific symptoms and signs among other strategies， so as to establish sepsis models that more closely resemble clinical reality and incorporate both TCM and western medical perspectives.

Background::Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs.Methods::We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians’ recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs.Results::A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility ( n = 3304, 43.1%) and a lack of trust in primary healthcare institutions ( n = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half ( n = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs. Conclusions::Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

Objective Based on the network pharmacology and animal experiments,to investigate the protective effect and possible molecular mechanism of ethanol extract from Atractylodes lancea on liver function in mice with liver fibrosis induced by bile duct ligation.Methods The main active ingredients atractylodin,atractylenolide Ⅰ,Ⅱ and Ⅱ from Atractylodes lancea were selected,which had been verified by literature and experiments,and the targets of these active ingredients were obtained through the SwissTargetPrediction database.The liver fibrosis disease targets were obtained through On-line Mendelian Inheritance in Man (OMIM),DisGeNET and GeneCards databases.The targets were added to the Wei Sheng Xin platform to find the intersection target for Atractylodes lancea in treating liver fibrosis.Cytoscape 3.10.1 was used to construct the "drug-component-target-disease" network diagram and protein-protein interaction core target network diagram.GO functional enrichment analysis and KEGG pathway analysis were performed,and molecular docking was performed between active components and core targets.Liver fibrosis was induced in mice by bile duct ligation,and liver function markers were measured.Results A total of 91 corresponding targets of atractylodin,atractylenolide Ⅰ,Ⅱ and Ⅲ and 9296 liver fibrosis disease targets were obtained,including 74 intersecting targets and 31 core targets.KEGG enrichment analysis showed that the main signaling pathways involved included inflammatory pathways such as epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt).Molecular docking results showed that the active ingredients had strong binding activity with the core target protein.The results of animal experiments showed that,compared with the sham surgery group,the model group displayed notable,the liver index,spleen index,activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST),degree of liver fibrosis,mRNA and protein expression of α-smooth muscle actin (α-SMA) and recombinant collagen type Ⅰ alpha 1 (COL1A1),and mRNA of recombinant collagen type Ⅳ alpha 2 (COL4A2) were significantly increased,and the thymus index was sigficantly decreased (P<0.05);compared with the model group,the liver injury of mice in the Atractylodes lancea administration group reduced liver injury,its liver index,spleen index,activity of serum ALT and AST,degree of liver fibrosis,mRNA and protein expression of α-SMA and COL1A1,and mRNA of COL4A2 were significantly decreased,and the thymus index was sigficantly increased (P<0.05).Conclusion Atractylodes lancea can improve liver function and alleviate tissue pathological damage in mice with liver fibrosis,which may be related to activating pathways such as PI3K/Akt,inhibiting oxidative stress and inflammatory reactions,and intervening in liver fibrosis.