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.

Objective:To analyze the clinical characteristics and prognosis of children with hematological malignancies complicated by secondary hemophagocytic lymphohistiocytosis(HLH).Methods:A total of 67 children with HLH admitted to Jinan Second Maternal and Child Health Hospital between June 2020 and June 2024 were selected.Children without hematological malignancies were divided into the non-combined group,and those with hematological malignancies were divided into the combined group.The clinical characteristics and prognosis of the two groups were analyzed.Results:There were no significant differences in clinical characteristics such as WBC,Hb,PLT between the two groups(P＞0.05).During the follow-up,the 1-and 2-year overall survival(OS)rates for all children were(88.6±4.1)％and(73.1±7.7)％,respectively.In the non-combined group,43 children survived and 6 died,with 1-and 2-year OS rates of(95.2±3.3)％and(77.4±9.3)％,respectively.In the combined group,12 children survived and 6 died,with 1-and 2-year OS rates of(71.8±10.7)％and(62.8±12.6)％,respectively.The OS rate of the combined group was significantly lower than that of the non-combined group(x2=4.787,P=0.029).The 1-and 2-year event free survival(EFS)rates of the combined group were(61.1±11.5)％and(50.9±13.3)％,respectively.Conclusion:Children with hematological malignancies complicated by secondary HLH exhibit complex and diverse clinical characteristics.Although favorable short-term therapeutic effects can be achieved,their long-term prognosis tends to be less optimistic.

Objective:To investigate the iodine nutrition status of children and pregnant women in different water iodine areas of Shandong Province.Methods:From February to September 2023, Leling City (iodine deficient), Gaotang County (moderate iodine), and Liangshan County (high iodine) in different water iodine areas of Shandong Province were selected as survey sites. One village was selected from each county (city) in five directions: east, west, south, north, and center. Forty children aged 8 to 10 years (balanced in age, half male and half female) and 20 pregnant women were selected as survey subjects in each village. Random urine samples of children and pregnant women were collected to test for urinary iodine. Meanwhile, thyroid examinations were conducted on children to calculate the goiter rate.Results:A total of 600 urine samples of children were tested, with a median urinary iodine level of 246.0 μg/L. The median urinary iodine levels of children in iodine deficient, moderate iodine and high iodine areas were 219.6, 208.0 and 446.0 μg/L, respectively ( n = 200, 200, 200). The median urinary iodine level of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 600 children underwent thyroid examinations, with a goiter rate of 5.8% (35/600). The goiter rate of children in iodine deficient, moderate iodine, and high iodine areas were 4.0% (8/200), 1.0% (2/200), and 12.5% (25/200), respectively. The goiter rate of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 247 urine samples of pregnant women were tested, with a median urinary iodine level of 158.2 μg/L. The median urinary iodine levels of pregnant women in iodine deficient, moderate iodine, and high iodine areas were 75.3, 175.2 and 321.2 μg/L, respectively ( n = 98, 84, 65). The median urinary iodine level of pregnant women in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas, and the median urinary iodine level of pregnant women in moderate iodine area was significantly higher than that in iodine deficient area ( P < 0.05). Conclusion:The urinary iodine levels of children and pregnant women and the goiter rate of children in high iodine area of Shandong Province are significantly increased, and water iodine may be a key factor affecting the iodine nutrition status of the population.

Natural products are an important source for innovative drugs,but unclear molecular targets and mechanisms limit their further development and application.The authors proposed a new method for the target identification of natural products based on proteolysis-targeting chimera(PROTAC)technology and quantitative proteomics,and established the targeted degradomics(TGDO) technology for the identification of weak-affinity tar-gets.This article summarizes the standardized workflow and the application of TGDO for target identification of natural products.

Natural products are an important source for innovative drugs,but unclear molecular targets and mechanisms limit their further development and application.The authors proposed a new method for the target identification of natural products based on proteolysis-targeting chimera(PROTAC)technology and quantitative proteomics,and established the targeted degradomics(TGDO) technology for the identification of weak-affinity tar-gets.This article summarizes the standardized workflow and the application of TGDO for target identification of natural products.

Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia(BPD)at postmenstrual age(PMA)36 weeks,screen potential biomarkers and associated metabolic pathways,and assess their relationship with short-term respiratory outcomes.Methods A retrospective case-control study was conducted.Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included.Twenty infants with BPD and 20 gestational age-,birth weight-,and sex-matched non-BPD preterm infants were included.Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis,and associations with short-term respiratory outcomes were analyzed.Results Thirteen potential biomarkers distinguishing BPD were identified(area under the curve>0.75,P<0.05).Eight biomarkers—including terephthalic acid,phosphatidylinositol,fumarate,and lysophosphatidic acid—were significantly upregulated(FC≥1.5),while five biomarkers,such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine,were significantly downregulated(FC≤1/1.5).Pathway analysis indicated five pathways associated with BPD,including glycerophospholipid metabolism and phenylalanine metabolism.Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD.Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD.Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.

Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia(BPD)at postmenstrual age(PMA)36 weeks,screen potential biomarkers and associated metabolic pathways,and assess their relationship with short-term respiratory outcomes.Methods A retrospective case-control study was conducted.Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included.Twenty infants with BPD and 20 gestational age-,birth weight-,and sex-matched non-BPD preterm infants were included.Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis,and associations with short-term respiratory outcomes were analyzed.Results Thirteen potential biomarkers distinguishing BPD were identified(area under the curve>0.75,P<0.05).Eight biomarkers—including terephthalic acid,phosphatidylinositol,fumarate,and lysophosphatidic acid—were significantly upregulated(FC≥1.5),while five biomarkers,such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine,were significantly downregulated(FC≤1/1.5).Pathway analysis indicated five pathways associated with BPD,including glycerophospholipid metabolism and phenylalanine metabolism.Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD.Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD.Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.

Objective:To analyze the clinical characteristics and prognosis of children with hematological malignancies complicated by secondary hemophagocytic lymphohistiocytosis(HLH).Methods:A total of 67 children with HLH admitted to Jinan Second Maternal and Child Health Hospital between June 2020 and June 2024 were selected.Children without hematological malignancies were divided into the non-combined group,and those with hematological malignancies were divided into the combined group.The clinical characteristics and prognosis of the two groups were analyzed.Results:There were no significant differences in clinical characteristics such as WBC,Hb,PLT between the two groups(P＞0.05).During the follow-up,the 1-and 2-year overall survival(OS)rates for all children were(88.6±4.1)％and(73.1±7.7)％,respectively.In the non-combined group,43 children survived and 6 died,with 1-and 2-year OS rates of(95.2±3.3)％and(77.4±9.3)％,respectively.In the combined group,12 children survived and 6 died,with 1-and 2-year OS rates of(71.8±10.7)％and(62.8±12.6)％,respectively.The OS rate of the combined group was significantly lower than that of the non-combined group(x2=4.787,P=0.029).The 1-and 2-year event free survival(EFS)rates of the combined group were(61.1±11.5)％and(50.9±13.3)％,respectively.Conclusion:Children with hematological malignancies complicated by secondary HLH exhibit complex and diverse clinical characteristics.Although favorable short-term therapeutic effects can be achieved,their long-term prognosis tends to be less optimistic.

Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.

Objective:To investigate the changes of nitric oxide(NO),endothelin-1(ET-1),thromboxane B2(TXB2)levels in patients with chronic heart failure(CHF)and their correlation with plasma brain natriuretic peptide(BNP).Methods:We enrolled 110 CHF patients admitted in the Second Hospital of Qinhuangdao between January and December 2022.According to the New York Heart Association(NYHA)cardiac function classification,the patients were divided into cardiac function class Ⅱ group(n=22),cardiac function class Ⅲ group(n=50),and cardiac function class Ⅳ group(n=38).Baseline data,levels of NO,ET-1,TXB2,BNP and other related laboratory indexes were compared among three groups.Pearson correlation analysis was used to analyze the association of NO,ET-1,TXB2 with plasma BNP in CHF patients.Multivariate linear regression was employed to analyze related factors of elevated BNP in CHF patients.Results:Compared with patients in class Ⅱ group and class Ⅲ group,those in class Ⅳ group had significant higher uric acid[(467.39±32.60)μmol/L vs.(367.25±22.39)μmol/L vs.(421.42±28.34)μmol/L],total bilirubin[(17.36±3.10)μmol/L vs.(10.65±1.39)μmol/L vs.(11.12±2.01)μmol/L],BNP[(897.60±50.11)ng/L vs.(381.37±31.25)ng/L vs.(527.60±47.84)ng/L],NO[(50.12±5.95)μmol/L vs.(25.36±2.14)μmol/L vs.(37.92±4.84)μmol/L],ET-1[(114.10±10.53)pg/L vs.(80.25±7.38)pg/L vs.(97.03±8.40)pg/L],TXB2[(417.98±29.35)pg/ml vs.(302.63±19.63)pg/ml vs.(381.29±26.44)pg/ml](P＜0.001 all).Compared with those in class Ⅱ group,those in class Ⅲ group had significant higher above-mentioned indexes(except total bilirubin)(P＜0.001 all).Pearson correlation analysis indicated that plasma NO,ET-1,TXB2 were positively associated with BNP(r=0.828,0.750,0.720,P＜0.001 all).Multivariate linear regression analysis indicated that uric acid,total bilirubin,plasma NO,ET-1 and TXB2 levels were independent risk factors for elevated BNP level in CHF patients(B=0.555～20.550,P＜0.05 or＜0.01),while the use of angiotensin converting enzyme inhibitors(ACEI)/angiotensin Ⅱ receptor blockers(ARB)was an independent protective factor(B=-46.222,P=0.027).Conclusion:The levels of NO,ET-1,and TXB2 are closely related to the occurrence and development of CHF,and they show an increasing trend with the progression of CHF,and is closely related to BNP.