ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

Objective: To explore the longitudinal relationship between bullying victimization and sleep quality among rural boarding junior high school students in Hebei Province, and to investigate the chain mediated role of loneliness and rumination, so as to provide evidence for promoting sleep health in the population. Methods: A baseline survey was conducted in May, 2023 (T1) by convenient sampling method, and two rounds of longitudinal surveys were conducted in November, 2023 (T2) and May, 2024 (T3) among students in two rural boarding junior high schools in Hebei Province, and a sample of 601 students who completed all the surveys was finally obtained. Students completed questionnaires, including the Delaware Bullying Victimization Scale Student (DBVS-S), the University of California at Los Angeles Loneliness Scale (UCLA), the Ruminative Responses Scale, and the Pittsburgh Sleep Quality Index (PSQI). Group differences were examined by using t-test or ANOVA, correlations between variables were analyzed by using Pearson correlation coefficients, and a serial mediation structural equation model was constructed, with mediation effects tested via the Bootstrap method. Results: Female students scored higher on sleep quality than male students (7.47±2.70, 6.47 ±2.46, t =4.74, P <0.01). Pearson correlation analysis indicated that bullying victimization was positively correlated with loneliness, rumination, and sleep quality; loneliness was positively correlated with rumination and sleep quality; and rumination was positively correlated with sleep quality ( r =0.26, 0.33, 0.23; 0.39, 0.38; 0.54, all P <0.01). Mediation analysis showed that T2 loneliness had an independent mediating effect of 0.70 (95% CI =0.36-1.35) between T1 bullying victimization and T3 sleep quality, T2 rumination had an independent mediating effect of 1.34 (95% CI =0.71-2.45), and the serial mediation effect of T2 loneliness and T2 rumination was 0.64 (95% CI =0.37-1.13), accounting for 22.11% of the total effect (all P <0.01). Conclusions Bullying victimization adversely affects sleep quality among rural boarding junior high school students through a longitudinal chain mediating pathway involving loneliness and rumination. Psychological interventions should be strengthened for students who experience bullying to alleviate their loneliness and reduce rumination, thereby improving sleep quality.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

Childhood primary renal tubular diseases are chronic kidney diseases characterized by impaired renal tubular reabsorption. Primary renal tubular disease has diverse clinical manifestations and lacks of specificity. Laboratory tests are limited，making it prone to missed diagnosis and misdiagnosis. Based on the current knowledge of renal tubular diseases，authors propose early warning signals of renal tubular diseases such as family history of primary tubular diseases，unexplained polyhydramnios during pregnancy，polydipsia，polyuria，delayed growth and development or rickets，decreased muscle strength and tone，unexplained electrolyte disturbance，hyperuricemia，acid-base disturbance，positive urine sugar test，renal tubular proteinuria，urinary imaging examination suggesting kidney stones，calcium deposition，renal cysts and early onset of eye，ear，joint and neuron injury.Meanwhile，some universal management strategies for primary renal tubular disease are proposed，emphasizing the importance of multidisciplinary collaboration，genetic testing and individualized intervention to improve the long-term prognosis of childhood primary renal tubular diseases.

Objective To investigate the correlation of serum human epididymis protein 4(HE4)and lung injury Prediction(LIPS)score with sepsis-associated acute respiratory distress syndrome(ARDS)and 28 d mortality.Methods A total of 207 patients with sepsis admitted to the hospital from January 2021 to January 2024 were selected.According to the presence or absence of ARDS,the patients were divided into ARDS group(73 cases)and non-ARDS group(134 cases).According to the 28 d survival,the ARDS group was further di-vided into death group(26 cases)and survival group(47 cases).HE4 level was detected by electrochemilumi-nescence,and LIPS score was calculated.Multivariate Logistic regression model was used to analyze the influ-encing factors of death in ARDS patients.Point biserial correlation was used to analyze the correlation between serum HE4,LIPS score and 28 d death in ARDS patients.The receiver operating characteristic(ROC)curve was used to evaluate the value of serum HE4 and LIPS score in the diagnosis of sepsis-associated ARDS and predicting 28 d mortality.Results Compared with non-ARDS group,the serum HE4 level and LIPS score were significantly increased in ARDS group(P<0.05).The independent risk factors for sepsis-associated ARDS were increased SOFA score,increased blood lactic acid,increased HE4 and increased LIPS score(P<0.05).The 28 d mortality of 73 patients with sepsis-associated ARDS was 35.62%(26/73).Compared with the survival group,the serum HE4 and LIPS scores were increased in the death group(P<0.05).Serum HE4 and LIPS scores were positively correlated with 28 d mortality in patients with sepsis-associated ARDS(r=0.605,0.579,P<0.05).The area under the curve(AUC)of serum HE4 combined with LIPS score in the di-agnosis of sepsis-associated ARDS was 0.909,which was larger than 0.828 and 0.806 of serum HE4 and LIPS score alone(Z=3.360,3.387,all P<0.05).The AUC of serum HE4 combined with LIPS score in predicting 28 d mortality of patients with sepsis-associated ARDS was 0.891,which was larger than 0.808 and 0.779 of by serum HE4 and LIPS score alone(Z=2.028,2.017,all P<0.05).Conclusion The elevated serum HE4 level and LIPS score are independent risk factors for sepsis-associated ARDS,and are closely related to 28 d mortality.The combination of serum HE4 and LIPS score has a high value in the diagnosis of sepsis-associated ARDS and the prediction of 28 d mortality.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective:To investigate the mechanism of Polygonati Rhizoma-Angelicae Sinensis Radix in the treatment of prediabetes based on network pharmacology and animal experiments.Methods:The active components of Polygonati Rhizoma and Angelicae Sinensis Radix were retrieved from the TCMSP database. The potential targets of the active components were predicted using the Swiss Target Prediction database. The "drug-active component-target" network was constructed by Cytoscape 3.10 software. The disease targets were obtained from OMIM, Genecards, TTD and the U.S. National Library of Medicine. The common targets of drugs and diseases were screened by Venny 2.1.0 platform and imported into STRING database to construct the PPI network. The DAVID database was employed to perform Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on the common targets of drugs and diseases. The prediabetes model was established by feeding C57BL/6J mice with high-fat diet. 24 high-fat fed mice were divided into four groups using a random number table: the model group, Polygonati Rhizoma group, Angelicae Sinensis Radix group and Polygonati Rhizoma-Angelicae Sinensis Radix group (herb pair group), with 6 mice in each group. Another 6 normal mice were set as the normal group. Polygonati Rhizoma group was intragastrically administered with Polygonati Rhizoma granule solution at 2.055 g/kg, the Angelicae Sinensis Radix group was intragastrically administered with Angelicae Sinensis Radix granule solution at 2.055 g/kg, and the herb pair group was intragastrically administered with Polygonati Rhizoma-Angelicae Sinensis Radix herb pair at 4.11 g/kg, once daily. The model group and the normal group were intragastrically administered with an equal volume of deionized water for 10 weeks. Fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were regularly performed. After 10 weeks of intragastric administration, the levels of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting insulin (FINS) were measured; glycogen deposition in liver tissues was observed using periodic acid-Schiff (PAS); the mRNA expression levels of FGF1, FGF2, PGF, KDR, IGF1R, INSR, PI3Kca, PI3Kcb, PI3Kcg, Akt1, Akt2 and GSK-3β in liver tissues were detected by Real-time PCR; the protein expression levels of PI3K, phosphorylated (p)-Akt, Akt, p-GSK-3β and GSK-3β in liver tissues of mice were detected by Western blot.Results:205 core targets of Polygonati Rhizoma-Angelicae Sinensis Radix in the treatment of prediabetes were identified; KEGG enrichment analysis revealed that the herb pair may exert hypoglycemic effects by activating the PI3K-Akt signaling pathway. Compared with the model group, the FBG level and AUC values in the herb pair group decreased ( P<0.05), the levels of LDL-C and HDL-C decreased ( P<0.01), the FINS and HOMA-IR levels decreased ( P<0.05), the mRNA expression levels of FGF1, FGF2, PGF, KDR, IGF1R, INSR, PI3Kca, PI3Kcb, PI3Kcg, Akt1, Akt2 and GSK-3β in liver tissues were elevated significantly ( P<0.01), and the protein expression levels of PI3K/β-actin, p-Akt/Akt and p-GSK-3β/GSK-3β in liver tissues of the herb pair group significantly increased ( P<0.01). Conclusion:Polygonati Rhizoma-Angelicae Sinensis Radix may activate PI3K/Akt/GSK-3β signaling pathway by up-regulating FGF1, FGF2, PGF, etc., and affect insulin resistance, glycogen synthesis and other processes, so as to treat prediabetes.