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）.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective This study investigated the diversity of rodent populations and the infection status of Bartonella at three ports along the China-Mongolia border in 2022. Methods Rodents at three Belt and Road ports along the China-Mongolia border, namely Ganqimaodu, Erenhot, and Zhuengadabuqi, were morphologically identified. The Bartonella citrate synthase(gltA)gene was amplified by nested polymerase chain reaction(PCR), and PCR-positive products were sequenced. The resulting sequences were then analyzed for genetic characteristics. Phylogenetic analysis was performed using MEGA 11.0 software using Neighbor-Joining and Maximum-Likelihood method. Results A total of 94 rodents were captured, representing seven species from five families and six genera: Mus musculus, Meriones unguiculatus, Meriones meridianus, Spermophilus dauricus, Allactaga sibirica, Dipus sagitta, and Phodopus roborovskii. Among them, M. unguiculatus was the most abundant species, with 58 rodents, accounting for 61.70% of the total. Overall,11 positive Bartonella pathogen sequences were obtained from the three ports, with a positive detection rate of 11.70%(11/94). The infected rodent species included M. unguiculatus, M. meridianus, and A. sibirica, and two species of Bartonella were detected. Conclusions Rodents at Ganqimaodu, Erenhot, and Zhuengadabuqi ports along the China-Mongolia border were naturally infected with Bartonella. Rodent monitoring and pathogen prevention and control in this area should be strengthened.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Over the past three decades， China has made significant progress in the prevention and control of viral hepatitis， and the incidence rates of new-onset pediatric hepatitis B virus infections and acute viral hepatitis in the population have reduced to a relatively low level； however， there is still a heavy disease burden of chronic viral hepatitis in China， which severely affects the health status of the population. This study systematically summarizes the achievements of viral hepatitis prevention and control in China， analyzes existing problems and challenges， and proposes comprehensive prevention and control strategies and measures to eliminate viral hepatitis as a public health threat based on the national conditions of China， in order to provide a reference for related departments in China on how to achieve the action targets for eliminating viral hepatitis as a public health threat by 2030.

Objective To investigate the effect and potential mechanism of chimeric antigen receptor(CAR)-natural killer(NK)cell therapy on the growth of gastric cancer cells and xenograft tumors.Methods Cell experiments:The gastric cancer cell lines of SGC7901 and MGC803 were co-cultured with CAR-NK cells as the CAR-NK group,the NK cells were co-cultured with SGC7901 and MGC803 cells as the NK group,respectively.The mRNA levels of PD-1 and PD-L1 in both groups were detected by RT-qPCR.The cell proliferation ability was assessed using EdU staining and CCK-8 assay.The cell migration and invasion abilities were detected by Transwell assay.The change of cell cycle was detected by flow cytometry.The expression of PD-1 and PD-L1 proteins in cells was detected by Western blot.Animal experiments:Mice were established model of xenograft tumors and divided into the blank control group(inoculated with routinely cultured SGC7901 cells),NK treatment group(inoculated SGC7901 cells combined NK cells),CAR-NK treatment group(inoculated SGC7901 cells combined CAR-NK cells),CAR-NK+rhPD-1 treatment group(inoculated SGC7901 cells combined CAR-NK cells,with intraperitoneal injection of 5 mg/kg rhPD-1 concurrently),and CAR-NK+rhPD-L1 treatment group(inoculated SGC7901 cells combined CAR-NK cells,with intraperitoneal injection of 5 mg/kg rhPD-L1 concurrently),with 5 mice in each group.The tumor volume of each group was observed,the tumor weight was recorded,and the expression of PD-1 and PD-L1 proteins in the tumor tissue of each group were detected by Western blot.Results Compared to the NK group,the CAR-NK group showed significantly decreased proliferation rate,and numbers of migration and invasion of SGC7901 and MGC803 cells(P<0.05).Compared to the NK group,the number of S phase cells increased,while G2/M phase cells decreased in the CAR-NK group(P<0.05).Compared to the NK group,the mRNA and protein expression levels of PD-1 and PD-L1 significantly downregulated in SGC7901 cell of the CAR-NK group(P<0.05).In the xenograft mouse model,compared to the NK treatment group,the protein expression of PD-1 and PD-L1 downregulated in the tumor tissues of the CAR-NK treatment group,with smaller tumor volume and decreased tumor weight,the differences were statistically significant(P<0.05).Compared to the blank control group,the CAR-NK treatment group exhibited downregulated protein expression of PD-1 and PD-L1 in tumor tissues,reduced tumor volume,and decreased tumor weight,with statistically significant differences(P<0.05).Compared to the CAR-NK treatment group,the CAR-NK+rhPD-1 treatment group showed upregulated expression of PD-1 protein,large tumor volume,and increased tumor weight,with statistically significant differences(P<0.05).Compared to the CAR-NK treatment group,the CAR-NK+rhPD-L1 treatment group exhibited upregulated expression of PD-L1 protein,large tumor volume,and increased tumor weight,with statistically significant differences(P<0.05).Conclusion CAR-NK cell therapy have a significant inhibitory effect on the proliferation,migration,and invasion of gastric cancer cells,resulting in the gastric cancer cell cycle arrest,which may inhibit the growth of xenograft tumors by inhibiting the PD-1/PD-L1 axis.

Objective:To explore the effect of continuous improvement model with Definition,Measure,Analyze,Improve,and Control(DMAIC)on the management for equipment of diagnosing and treating chronic respiratory diseases.Method:To address the management issues of diagnosis and treatment equipment for chronic respiratory diseases,multiple management strategies were formulated on the basis of definition,measurement,analysis,improvement and control stages of the DMAIC continuous improvement model.Selected 80 diagnostic and therapeutic equipment used at the department of respiratory in People's Hospital of Xinjiang Uygur Autonomous Region from August 2021 to July 2023.The conventional management method was used to manage them during August 2021 to July 2022,and the management method of DMAIC continuous improvement management model(continuous improvement management method)for chronic respiratory diseases was adopted to manage them during August 2022 to July 2023.The ratio of failure equipment,score of risk assessment,qualified rate of examination,and satisfaction score of users who operated equipment by using the two kinds of management methods were compared.Result:The average failure ratios of shutdown due to failure,injury that caused external environment,abnormal self-examination at power on,unqualified quality inspection,and poorly operational quality in treatment in equipment of diagnosing and treating respiratory disease by using continuous improvement management method were respectively(1.58±0.51)%,(0.34±0.10)%,(0.65±0.20)%,(2.08±0.53)%and(1.61±0.52)%,which were all lower than those by using conventional management method,and the differences of them were significant(t=14.512,11.205,24.354,17.169,17.663,P<0.05).The degree of detectability,severity,and probability scores of occurrence of the equipment by using continuous improvement management method were lower than those of conventional management method,and the differences were statistically significant(t=10.478,6.930,9.407,P<0.05).The qualified rate of equipment inspection of continuous improvement management method was higher than that of conventional management method,and the difference was statistically significant(x2=9.642,P<0.05).The performance,cleanliness of equipment,and timeliness scores of operators,who used equipment,for diagnosis and treatment equipment that were managed by using continuous improvement management method were all higher than those by using conventional management method,and the differences were statistically significant(t=2.204,2.268,2.604,P<0.05).Conclusion:The DMAIC continuous improvement management model method for equipment of diagnosing and treating chronic respiratory disease can significantly improve management level for equipment,and reduce failure risk of equipment,and increase the utilization efficiency of equipment and the users'satisfaction.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To investigate the association between nutritional status and serum hepcidin and pentraxin 3(PTX3)levels in patients undergoing maintenance hemodialysis(MHD).Methods A total of 76 patients with MHD who met the inclusion criteria were recruited from the hemodialysis center at the Affiliated Hospital of Chengde Medical University.Nutritional status was assessed using the Subjective Global Assessment(SGA),which categorizes patients into three grades:SGA-A,SGA-B,and SGA-C.Serum levels of PTX3 and hepcidin were mea-sured by enzyme-linked immunosorbent assay(ELISA).Statistical analyses were conducted using SPSS software.One-way analysis of variance(ANOVA)was applied to compare differences across the three SGA groups.Logistic regression analysis was performed to identify influencing factors,and receiver operating characteristic(ROC)curve analysis was used to evaluate diagnostic value.Among the participants,45 patients were classified as malnourished based on SGA-B and SGA-C scores,while those with SGA-A constituted the well-nourished control group.Results Among the 76 MHD patients,59.2%were malnourished.We then compared clinical characteristics across the three groups.The results showed that the malnourished group was older and exhibited significantly higher levels of hs-CRP,PTX3,and hepcidin(P<0.05),while serum albumin,creatinine,and phosphorus levels were significantly lower(P<0.05).Pearson correlation analysis revealed positive correlations between SGA grades and hs-CRP,PTX3,and hepcidin levels(all P<0.05).Logistic regression analysis with"malnutrition"as the dependent variable indicated that elevated hs-CRP,PTX3,and hepcidin levels,along with age and male gender,were associated with increased risk of malnutrition in MHD patients,whereas higher serum phosphorus and creatinine levels were protec-tive factors.Further multivariate logistic regression analysis demonstrated that serum PTX3 level was an independent risk factor for malnutrition(P=0.032),while higher creatinine level was an independent protective factor(P=0.047).ROC curve analysis showed that the combination of serum PTX3 and creatinine levels had a high diagnostic value for identifying malnutrition in MHD patients,yielding an AUC of 0.789(P<0.001),a Youden index of 0.448,sensitivity of 77.8%,and specificity of 71.0%.Conclusions Elevated levels of PTX3 and hepcidin,along with reduced serum creatinine levels,are associated with an increased risk of malnutrition in patients undergoing MHD.Notably,elevated serum PTX3 and decreased serum creatinine independently predict malnutrition in this population and demonstrate high predictive value.

Immunogenic cell death(ICD)is a form of cell death that can activate the immune system,especially in the treatment of cancer.ICD can enhance the recognition of tumors by the immune system and the release of damage associated molecular patterns(DAMPs),to achieve tumor cell death.Oncolytic viruses(OVs)can selectively infect and kill tumor cells without damaging normal cells.OVs are type Ⅱ ICD inducers that induce ICD in tumor cells by targeting the endoplasmic reticulum.Here,we review the characteristics of ICD and the mechanism of ICD induction by OVs.We also review the latest clinical progress involving ICD and discuss future treatment strategies for tumors.