ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.

Objective: This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery. Methods: This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression. Results: Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability. Conclusion Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.

Thyroid dysfunction(TD)is a prevalent disorder of the endocrine system.Owing to its non-specific clinical symptoms and the limitations inherent in current diagnostic approaches,there is a pressing need to further investigate its underlying pathogenesis and identify novel biomarkers.As a pivotal component of systems biology,omics technologies offer a promising avenue for uncovering the molecular mechanisms of TD by integrating high-throughput data.This thesis presents a comprehensive review of recent advancements in genomics,transcriptomics,proteomics,metabolomics,lipidomics,and multi-omics research related to TD.It examines genetic variations and epigenetic regulatory mechanisms from multiple molecular levels,including DNA,RNA,proteins,and metabolites.Furthermore,it elucidates the metabolic disturbances associated with TD and the modes of action of relevant therapeutic agents,contributing to the development of potential biomarkers and drug targets for early detection and intervention.By synthesizing findings across various omics platforms,this thesis aims to delineate the complex network interactions underlying TD and to provide valuable insights and strategies for future clinical management,as well as personalized diagnosis and treatment.

Objective To evaluate the diagnostic efficacy of sound touch viscoelastography(STVi)and shear wave elastography(SWE)in distinguishing between benign and malignant breast nodules.Methods A total of 104 breast nodules(52 benign and 52 malignant)from 102 patients scheduled for surgical treatment at Binzhou Medical University Hospital between October 2024 and February 2025 were prospectively enrolled.All nodules were pathologically confirmed through surgical excision or core needle biopsy.The viscosity coefficient and Young's modulus of both intranodular and perinodular tissues within a 2-mm range were measured using the Mindray Resona A20S ultrasound system.The diagnostic performance of each parameter,the correlation between elastic parameter values and the maximum nodule diameter,as well as the inter-correlation between the two parameters were systematically analyzed.Results The elasticity parameters were significantly higher in malignant nodules[maximum intranodular Viscosity coefficient(Vimax):5.93(4.33,8.47)Pa·s,maximum Young's modulus(Emax):81.18(58.31,120.33)kPa;maximum Viscosity coefficient of the surrounding 2-mm tissue(Vi2max):7.57(5.40,10.16)Pa·s,maximum Young's modulus(E2max):117.21(65.66,170.66)kPa]compared to benign nodules[Vimax:3.70(2.69,5.32)Pa·s,Emax:41.42(28.29,64.25)kPa;Vi2max:4.30(3.63,5.65)Pa·s,E2max:47.23(36.42,74.67)kPa](P<0.05).The diagnostic performance of the 2-mm perinodular tissue(Vi2max:0.78,E2max:0.81)surpassed that of intranodular tissue(Vimax:0.72,Emax:0.77)(P<0.05).The combined diagnostic model(Vi2+E2,Vi+E)achieved AUC values of 0.82 and 0.77,respectively,which outperformed STVi alone(P<0.05)and showed marginally better performance than SWE alone,although the difference was not statistically significant(P>0.05).The maximum nodule diameter showed a moderate correlation with the elasticity parameters,with E2max exhibiting the strongest correlation(r=0.510,P<0.05).Conclusions Both STVi and SWE show clinical value in distinguishing between benign and malignant breast nodules.Particularly,elasticity parameters obtained from the 2-mm perinodular tissue demonstrate better diagnostic performance than those measured within the nodule itself,and combining these parameters enhances the overall diagnostic accuracy of STVi.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective To study the effect of incorporating comprehensive geriatric assessment(CGA)into the whole-process WeChat-based case health management in elderly population who took annual physical examinations,thereby to improve their ability in health self-management.Methods A randomised controlled trial was conducted to select 100 elderly people who took annual physical examinations in our hospital from July 2022 to June 2023.The elderly were randomly divided into a control group and an trial group,with 50 people per group.CGA was applied to both groups,but the control group was under conventional health management,while the trial group received the incorporation of CGA into a whole-process WeChat-based case health management.The self-rated abilities for health practices scale(SRAHP)was used to compare the scores between the two groups before intervention,at 3,6 and 12 months after intervention.The scores of fatigue,resistance,ambulation,illnesses&loss of weight scale(FRAIL)and the mini nutritional assessment-short form(MNA-SF)were compared between the two groups before intervention and at 12 months after intervention.Incidence of falls was also evaluated after intervention.Results All the participants completed the study.Repeated measures analysis of variance showed that total SRAHP scores had statistical significances in main effect on time,group and interaction(Ftime=193.451,P<0.001;Fgroup=23.661,P<0.001;Finteraction=29.970,P<0.001).Further analysis revealed that the elderly in trial group had higher total scores in SRAHP than those in the control group at 6 and 12 months after intervention(both P<0.001).At 12 months after intervention,the trial group showed better scores in FRAIL and MNA-SF than the control group(both P<0.05)as well as with a lower incidence of falls(P<0.05).Conclusion Incorporation of CGA into a comprehensive WeChat-based case health management,over a long-term,can effectively enhance the ability in health self-management among elderly individuals who take annual health examinations,improve frailty and nutritional status and reduce the incidence of falls.The health self-management discovered from this study provides a valuable reference for health management among the elderly people who take annual physical examinations.

Objective To investigate the inhibitory effects of formononetin on sortase A(SrtA)of Staphylococcus epidermidis(S.epi-dermidis)and its biofilm formation.Methods Biofilm-producing S.epidermidis standard strain RP62A and biofilm-producing S.epider-midis clinical strains were collected.The minimal inhibitory concentration(MIC)of formononetin against S.epidermidis was investigated using the two-fold dilution method.The inhibitory effects of different concentrations of formononetin on the growth of S.epidermidis in vitro were studied by growth curve analysis using microplate reader.The cytotoxicity of formononetin was measured by cell culture.The biocompatibility of formononetin was studied by hemolysis assay.The inhibitory effect of formononetin on the activity of SrtA was deter-mined by fluorescence resonance energy transfer(FRET)assay.The effect of formononetin on the ability of S.epidermidis binding fi-bronectin was assessed by fibronectin binding assay.The effect of formononetin on the anchoring of serine-rich repeat proteins(SRRPs)in S.epidermidis was assessed by immunofluorescence staining.The effect of formononetin on the biofilm formation of S.epidermidis was measured by crystal violet staining.Results The MICs of formononetin against S.epidermidis were greater than 512 μg/mL.Compared with the control group,32 μg/mL of formononetin did not significantly affect the growth of S.epidermidis or reduce the viability of hu-man aortic endothelial cells.The hemolysis rate of human red blood cells was less than 5%.The inhibition rate of SrtA activity was ap-proximately 53.8%.The binding capacity of S.epidermidis to fibronectin was reduced by approximately 45.4%.Microscopic observation revealed a significant reduction in the anchoring of SRRP in S.epidermidis,and the formation of biofilm of S.epidermidis was inhibited by approximately 41.7%.Conclusion Formononetin inhibits the activity of SrtA in S.epidermidis,reduce its fibronectin-binding ca-pacity and biofilm formation,and thus represents a promising candidate for the prevention of S.epidermidis infections.