ObjectiveTo investigate the liver-protecting and anti-liver fibrosis effects of astragaloside Ⅳ （AS-Ⅳ） in vitro and in vivo， as well as its mechanism of action in intervention against liver fibrosis. MethodsIn the animal experiment， C57BL/6J mice were divided into control group， model group， low-dose AS-Ⅳ （20 mg/kg） group， and high-dose AS-Ⅳ （80 mg/kg） group. The mice were given intraperitoneal injection of carbon tetrachloride for 6 weeks to induce liver fibrosis， and since week 3 of injection， the mice in the low-dose AS-Ⅳ group and the high-dose AS-Ⅳ group were given AS-Ⅳ by gavage at a dose of 20 mg/kg and 80 mg/kg， respectively. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured after 4 weeks of administration， as well as the serum levels of hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ N-terminal peptide （PⅢNP）， and collagen type Ⅳ （Col-Ⅳ）. HE staining， picrosirius red staining， and Masson staining were used to observe liver histopathology and collagen deposition； RT-qPCR was used to measure the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue， and Western blot was used to measure the protein expression levels of α-smooth muscle actin （α-SMA）， collagen type Ⅲ （Col-Ⅲ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated PI3K （pPI3K）， protein kinase B （Akt）， and phosphorylated AKT （p-Akt） in liver tissue； transcriptome sequencing was performed for liver tissue to identify differentially expressed genes and perform a bioinformatics analysis. In the cell experiment， transforming growth factor-β （TGF-β） was used to induce the activation of LX-2 cells， and the PI3K inhibitor LY294002 and the PI3K activator 740 Y-P were used for intervention. The cells were divided into control group， model group， AS-Ⅳ group， LY294002 group， and AS-Ⅳ+740 Y-P group， and the cells were harvested after 36 hours of intervention. Changes in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K/PI3K， and pAkt/Akt in LX-2 cells were measured， as well as changes in the relative mRNA expression levels of Acta2， Col1a1， and Col3a1. 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. ResultsIn the animal experiment， compared with the model group， the AS-Ⅳ treatment group had significant reductions in the serum levels of ALT， AST， HA， LN， PⅢNP， and Col-Ⅳ （all P<0.01）， the mRNA expression levels of Acta2， Col1a1， and Col3a1 in liver tissue （all P<0.05）， and the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） in liver tissue （all P<0.05）. In the cell experiment， compared with the control group， the model group had significant increases in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） after TGF-β induction （all P<0.05）； compared with the model group， the AS-Ⅳ group had significant reductions in the protein expression levels of α-SMA， Col-Ⅲ， pPI3K， and pAkt （Ser473） （all P<0.05）， and both the AS-Ⅳ group and the LY294002 group had significant reductions in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， Col1a1， and Col3a1 （all P<0.05）. Compared with the AS-Ⅳ group， there were significant increases in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2， col1a1， and Col3a1 after 740 Y-P intervention （all P<0.05）. ConclusionAS-Ⅳ can inhibit hepatic stellate cell activation and improve liver fibrosis， possibly by inhibiting the PI3K/Akt signaling pathway.

Objective To investigate the prognosis and its influencing factors in patients with hypertension complicated with heart failure (HF). Methods A total of 381 patients with hypertension and HF who were treated in our hospital from March 2022 to April 2025 were chosen. The patients were followed up for the prognosis within 6 months and split into good prognosis group (n=266) and poor prognosis group (n=115). The clinical data of the two groups were compared and analyzed. Multivariate Logistic regression analysis was used to determine the influencing factors of poor prognosis. Results The group with poor prognosis had higher proportions of atrial fibrillation and New York Heart Association (NYHA) Class III-IV, as well as increased left ventricular end-diastolic diameter (LVED), left ventricular end-systolic diameter (LVES), interventricular septum thickness (IVS), and left ventricular posterior wall thickness (LVPW) compared to the group with good prognosis (P<0.05). Additionally, levels of systolic blood pressure (SBP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), total cholesterol (TC), low-density lipoprotein (LDL), creatinine (Cr) were elevated (P<0.05), while left ventricular ejection fraction (LVEF) was decreased (P<0.05). NYHA classification, LVEF, LVED, LVPW, NT-proBNP were independent influencing factors of poor prognosis in patients with hypertension complicated with HF (P<0.05). Conclusion NYHA classification, LVEF, LVED, LVPW and NT-proBNP are closely related to the poor prognosis of patients with hypertension and HF.

It is believed that the root cause of vascular dementia lies in insufficient primal yang and weakness in the circulation of blood. The key pathological factors are the mutual stagnation of phlegm and blood stasis， and the obstruction of blood vessels. The general treatment principle is to tonify qi and promote yang， expel pathogenic factors， and unblock yang. This involves supplementing the innate and acquired yang qi of the spleen and kidneys， removing pathogenic factors like phlegm， turbidity， and blood stasis， in order to restore the function of yang qi and promote the circulation of blood and qi. The basic prescription for tonifying qi and promoting yang includes Heishunpian （Lycium Ruthenicum）， Zhichuanwu （Aconitum Carmichaelii）， Guizhi （Cinnamomum Cassia）， Renshen （Panax Ginseng）， and Huangqi （Astragalus Membranaceus）. Depending on the type of pathogenic excess， the treatment can be modified with Tongqiao Huoxue Decoction （通窍活血汤）， adding Yujin （Curcuma Longa） and Xiangfu （Cyperus Rotundus） to invigorate blood and promote yang， or with Fabanxia （Pinellia Ternata）， Chenpi （Citrus Reticulata）， Zhishi （Citrus Aurantium） plus Sijunzi Decoction （四君子汤） to resolve phlegm and promote yang. Both the root and branch are treated simultaneously. When yang qi is activated， blood and qi are nourished， and when pathogenic excess is expelled， the blood vessels are unblocked. This approach aims to provide a treatment strategy for vascular dementia.

In 1946, radioactive iodine 131 was first used for the treatment of differentiated thyroid cancer. However, the limitations of early nuclear medicine technology, the lack of specificity, the efficacy of nuclide therapy, and its adverse effects have limited its widespreadly clinical application. In recent years, scientists and clinicians have linked radioisotopes to targeted parts (tumor-specific small molecules, peptides, or antibodies) to develop safe and effective nuclear drugs. Ra-223, Lutathera (lutetium-177), and Pluvicto (¹⁷⁷Lu-PSMA-617) have been successfully used in clinical treatment. Radioligand therapy has gradually shown good efficacy in different tumors. This paper focuses on the current situation of the application of therapeutic radioligand drugs in advanced malignant tumors and the latest research results and treatment strategies to achieve more accurate and personalized treatment methods, thereby to improve the curative effect, and reduce adverse reactions.

Objective:To investigate ⅰ)the therapeutic effects of different doses of recombinant human prourokinase(rh-proUK)on patients with ST segment elevation myocardial infarction(STEMI)undergoing percutaneous coronary inter-vention(PCI),and ⅱ)its impact on peripheral blood P-selectin(CD62p)and Adropin levels.Methods:This randomized control study enrolled 132 STEMI patients undergoing PCI in Weinan Second Hospital between June 2020 and June 2023.Patients were randomly divided into control group(n=44,routine medication),low dose group(n=44,10 mg rh-proUK therapy)and high dose group(n=44,20 mg rh-proUK therapy).Therapeutic effective rate,myocardial perfu-sion immediate after operation,cardiac function,peripheral blood CD62p and Adropin levels,incidence of major adverse cardiovascular events(MACE)within 1 month after operation were compared among three groups.Results:Compared to patients in control group,those in high dose group had significantly higher total effective rate(95.5％vs.54.6％),pro-portions of TIMI myocardial perfusion grade(TMPG)grade 3(86.4％vs.25.0％)and ST segment resolution above 30％(∑STR≥30％)(88.6％vs.59.1％),stroke volume(SV)[(76.81±24.47)ml vs.(61.89±14.84)ml]and cardiac output(CO)[(6.48±1.45)L/min vs.(5.48±1.98)L/min],and significantly lower corrected TIMI frame count(CT-FC)[(31.80±6.32)frames vs.(52.39±7.14)frames],CD62p[(70.52±9.54)％vs.(82.42±12.44)％],Adropin[(82.48±9.55)pg/ml vs.(94.48±10.53)pg/ml]and total incidence of MACE(9.1％vs.38.6％)(P＜0.05 or＜0.01).Compared to those in low dose group,patients in high dose group had significantly higher total effective rate,pro-portions of TMPG grade 3 and ∑STR≥30％,SV and CO,and significantly lower CTFC,CD62p,Adropin and total inci-dence of MACE(P＜0.05 or＜0.01).Conclusion:The therapeutic effect of 20 mg rh-proUK on STEMI patients under-going PCI is significantly better than that of 10 mg,which could improve cardiac function,reduce CD62p,Adropin levels,and incidence of major adverse cardiovascular events.

Quality control of pediatric musculoskeletal ultrasound(MSKUS)must be integrated throughout the entire diagnostic process.Its core lies in a thorough understanding of the growth,development,and pathophysiological characteristics of the pediatric musculoskeletal system,mastery of MSKUS examination techniques,and the establishment of a systematic and comprehensive diagnostic framework.This review focuses on the core aspects of pre-examination,during examination,and post-examination to describe the quality control points and strategies for pediatric MSKUS.

Objective:To evaluate the role of silent information regulator factor 2-related enzyme 1 (SIRT1)/Klotho signaling pathway in renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods:Forty SPF healthy male rats, aged 6-8 weeks, weighing 140-170 g, were divided into 5 groups ( n=8 each) by the random number table method: non-diabetic sham operation group (NS group), non-diabetic I/R group (NIR group), diabetic sham operation group (DS group), diabetic I/R group (DIR group), and diabetic I/R + SIRT1 inhibitor EX-527 group (DIR+ EX-527 group). Diabetes mellitus was induced by intraperitoneal streptozotocin 60 mg/kg. The myocardial I/R was produced by temporary ligation of the left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. EX-527 5 mg/kg was intraperitoneally injected before ischemia and at 10 min before reperfusion in DIR+ EX-527 group. Serum levels of lactic dehydrogenase (LDH), cardiac troponin I (cTnI), malondialdehyde (MDA), superoxide dismutase (SOD), blood urea nitrogen (BUN) and creatinine (Cr) were determined at the end of reperfusion. Renal tissues were collected for observation of the pathological changes and for detection of the expression of SIRT1, Klotho, and interleukin-1 β (IL-1β) by Western blot. Results:Compared with NS group, the serum levels of LDH, cTnI, BUN and MDA were significantly increased, the serum levels of SOD were decreased, the expression of Klotho and SIRT1 was down-regulated, the expression of IL-1β was up-regulated ( P<0.05), and the pathological damage to renal tissues was marked in NIR group and DS group. Compared with DS group and NIR group, the serum levels of LDH, cTnI, BUN, Cr and MDA were significantly increased, the serum levels of SOD were decreased, the expression of Klotho and SIRT1 was down-regulated, the expression of IL-1β was up-regulated ( P<0.01), and the pathological damage to renal tissues was aggravated in DIR gruop. Compared with DIR gruop, the serum levels of LDH, cTnI, BUN, Cr and MDA were significantly increased, the level of serum SOD was decreased, the expression of Klotho and SIRT1 was down-regulated, the expression of IL-1β was up-regulated ( P<0.01), and the pathological damage to renal tissues was aggravated in DIR+ EX-527 group. Conclusions:Weakened activation of SIRT1/Klotho signaling pathway may be involved in the mechanism of myocardial I/R-induced renal injury in diabetic rats.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective:To investigate the effects of propionic acid produced by Akkermansia muciniphila on the radiosensitivity of colorectal cancer and the underlying mechanism. Methods:Normal human colon mucosal epithelial cells (NCM460) were used to determine the appropriate concentration of propionic acid. Human colorectal cancer cells (HCT-8) were treated with A. muciniphila-conditioned medium or propionic acid, followed by exposure to 6 Gy γ-ray irradiation, and cell survival and proliferation were measured by clone formation assay and Cell Counting Kit-8 (CCK-8) assay, respectively. A mouse model of colorectal cancer was established using azoxymethane/dextran sodium sulfate. The mice were divided into control model group, irradiation group, and irradiation+ propionic acid group. Their body weight, colorectal length, tumor count, and tumor area were recorded. The radiosensitizing effect of propionic acid was assessed with HE staining, immunohistochemical staining, and enzyme-linked immunosorbent assay. The mechanism was explored by using RT-PCR and flow cytometry. Results:CCK-8 assay showed that 1-mmol/L propionic acid had no significant effect on the proliferation of NCM460 cells ( P>0.05), which was used for subsequent experiments. Pretreated with A. muciniphila-conditioned medium or propionic acid, the survival and proliferation abilities of irradiated HCT cells were significantly decreased ( t=3.14-34.98, P<0.05). Compared with the irradiation group, the colorectal cancer mice in the irradiation+ propionic acid group showed a significantly longer colorectal length ( t=3.50, P<0.05) and a significantly smaller number of tumors ( t=3.48, P<0.05); the two groups had significantly smaller tumor areas than the control model group ( t=5.97, 7.30, P<0.05). HE staining and immunohistochemical staining showed that propionic acid restored colorectal structure, and decreased Ki67 expression in colorectal tissue ( t=14.50, 3.40, P<0.05). Propionic acid treatment significantly reduced the levels of the inflammatory factors interleukin-6 and tumor necrosis factor-α, as compared with the mice receiving irradiation alone ( t=4.86, 5.06, P<0.05). Irradiation plus propionic acid treatment significantly increased p53 expression and significantly aggravated G 2/M phase block and cell apoptosis ( t=20.35, 13.05, P<0.05). Conclusions:The A. muciniphila metabolite propionic acid plays a sensitizing role in radiation therapy for colorectal cancer by promoting G 2/M phase block and apoptosis in colorectal cancer cells.

Objective:To investigate the predictive value of interventricular septal thickness(IVST),the ratio of mitral ear-ly diastolic peak flow velocity to late diastolic peak flow velocity(E/A)combined with aortic valve flow velocity(AV)for hypertensive heart disease(HHD)and its association with blood pressure grade.Methods:A total of 202 patients with hy-pertension suspected of HHD admitted to Qinhuangdao Hospital of Dongfang Hospital,Beijing University of Chinese Medi-cine between May 2020 and May 2023 were enrolled and divided into HHD group(n=102)and non-HHD group(n=100)according to color Doppler energy imaging and blood pressure diagnosis.Blood pressure,IVST,E/A and AV were measured in two groups.The predictive value of IVST,E/A and AV for HHD were evaluated by receiver operating charac-teristic(ROC)curve.According to hypertension grading,patients in HHD group was divided into grade 1～2 group(n=59)and grade 3 group(n=41).The association of IVST,E/A,AV with blood pressure grade in HHD patients were ana-lyzed by Spearman correlation analysis.Results:Compared with patients in non-HHD group,those in HHD group had significant higher IVST,and significant lower E/A and AV(P＜0.001 all);Compared with patients in grade 1～2 group,those in grade 3 group had significant higher IVST,and significant lower E/A and AV(P＜0.001 all).ROC curve showed that the AUC of IVST,E/A and AV alone and their combination in HHD diagnosis was 0.798(95％CI 0.736～0.851),0.682(95％CI 0.613～0.746),0.810(95％CI 0.748～0.862)and 0.927(95％CI 0.881～0.959)respectively,and the diagnostic value of combined detection was significantly higher than those of single detections(Z=4.431,5.669,3.948,P=0.001 all).Spearman correlation analysis showed that E/A and AV were significant negatively correlated with blood pressure grade(r=-0.725,-0.781),while I VST was significant positively correlated with blood pressure grade(r=0.714),and combined detection possessed a stronger correlation with it in HHD patients(r=0.875,P＜0.001 all).Con-clusion:The combined detection of I VST,E/A and AV demonstrates a good predictive value for HHD and exhibits a sig-nificant correlation with blood pressure grade in HHD patients.