OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

OBJECTIVE: To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases. METHODS: Relevant studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, Sinomed , CNKI and Wanfang databases. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies, and relevant data were extracted. meta-analysis was performed using RevMan 5.4 and RStudio software, and forest plots were generated. RESULTS: Six randomized controlled trials (RCTs) were included. Compared with the control group, denosumab significantly reduced the risk of skeletal-related events (HR=0.78, 95% CI: 0.62-0.93). In terms of safety, denosumab did not increase the risk of total adverse events, severe adverse events and the adverse events higher than CTC grade 3. CONCLUSION Denosumab can delay the time to first skeletal-related event with good safety. However, due to the limitations of this study, further high-quality, large-sample, multicenter RCTs are needed to confirm these findings.
Humans ; Denosumab/therapeutic use* ; Bone Neoplasms/drug therapy* ; Prostatic Neoplasms/drug therapy* ; Male ; Randomized Controlled Trials as Topic ; Bone Density Conservation Agents/therapeutic use*

Background::The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods::This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results::The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P = 0.012). Conclusions::This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Objective:To evaluate the prognostic value of albumin-bilirubin(ALBI)score in patients with distal cholangiocarcinoma(dCCA)after radical surgery.Methods:This retrospective study analyzed clinical data from 156 patients diagnosed with distal cholangiocarcinoma who underwent surgical treatment at the Department of Hepatobiliary Surgery,Beijing Chaoyang Hospital,affiliated with Capital Medical University,between January 2014 and December 2022.All patients gave informed consent and medical ethics guidelines were followed.The Albumin-Bilirubin(ALBI)score was calculated based on preoperative serum albumin and total bilirubin levels.Patients were then stratified into low ALBI and high ALBI groups using the optimal cut-off value.The study aimed to assess and compare the long-term prognosis of patients in these groups and to identify risk factors that influence their long-term prognosis using univariate and multivariate analyses.Results:Using the optimal ALBI cut-off value,patients were stratified into a low ALBI group(ALBI≤-1.67,92 cases)and a high ALBI group(ALBI>-1.67,64 cases).The median survival time for patients in the low ALBI group was 33 months,while the median survival time for patients in the high ALBI group was 20 months.The overall survival rates at 1 year,3 years,and 5 years postoperatively were 85.4%,43.8%,and 35.8%for the low ALBI group,and 65.5%,23.4%,and 13.6%for the high ALBI group,respectively(χ2=8.882,P=0.003).Results from both univariate and multivariate analyses indicated that high ALBI,CA19-9>37U/ml and lymph node metastasis were independent risk factors of long-term postoperative survival.Conclusion:In patients with distal cholangiocarcinoma,the preoperative ALBI score may be an effective indicator for predicting long-term survival.

Rheumatoid arthritis （RA） is a systemic chronic auto-inflammatory disease， characterized by infiltration of inflammatory cells， pannus formation， articular cartilage destruction， and bone matrix destruction. Therefore， improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components， multiple targets， high activity and low side effects. Based on this， the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors， phosphatidylinositol 3-kinase/protein kinase B， Wnt/β- catenin， nuclear factor-κB， mitogen-activated protein kinase， Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor， microRNAs， fibroblastic synovial cells.

Zona Incerta ; Prefrontal Cortex ; Fear ; Neural Pathways

Lipid-based nanocarrier is a classic drug delivery system with great biocompatibility and biodegradability. It can effectively reduce the toxicity of anti-tumor and anti-infective drugs in clinical practice. However, it has not yet met the clinical demand for enhanced therapeutic efficacy, and the clinical application is still very limited. The complex in vivo delivery process of lipid-based nanomedicine and the reciprocal interactions with body lead to unexpected changes in in vivo performance of nanomedicine and seriously hinder clinical translation. Therefore, the in-depth study of the relationships among intrinsic properties of lipid-based nanomedicine, the in vivo delivery process, and the regulatory mechanisms will not only provide guidance for the rational design of nanocarriers, but also promote the clinical translation and precision medicine of new lipid-based nanomedicine. In this review, we summarize the in vivo delivery process, regulating factors and intervention strategies for the in vivo delivery of lipid-based nanomedicine.

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

Objective To investigate the pharmacodynamic effects of Poria triterpenes on tumor suppression in mice with ascites tumors,and to detect and identify the chemical components of Poria triterpenes using HPLC-LTQ-Orbitrap method,and to explore the potential mechanism of action of Poria triterpenes on tumor suppression in mice with ascites tumors based on both of them using non-labeled definitive proteomics techniques.Methods Poria triterpene parts were extracted by solvent method,and the main components were detected and identified by HPLC-LTQ-Orbitrap liquid mass spectrometer;mice were randomly divided into model group,Poria triterpene group and positive control group(mushroom polysaccharide group),after 21 days of continuous administration,to establish After continuous administration for 21 days,the H22 ascites tumor mouse model was established,and the effect of each drug group on the amount of ascites,spleen index,thymus index,liver index,serum TNF-Alpha and IL-2 in H22 ascites tumor mice was observed after one week of continued administration;then H22 cells were extracted from the ascites of mice,and the H22 cells in the model group and Poria triterpene group were detected by non-lable-free quantitative proteomics technique.The differentially expressed proteins(DEPs)were screened out by using GO,KEGG and other analyses.Results The abdominal water volume in the mouse Poria triterpene group was significantly lower than that in the model group(P<0.05);the thymus index in the mouse Poria triterpene group was significantly higher than that in the model group(P<0.05);the serum levels of TNF-Alpha in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01),and the serum levels of IL-2 in the mouse Poria triterpene group were significantly different from those in the model group(P<0.01).Through the analysis of the chemical composition of Poria triterpene parts,a total of 19 triterpenoids were identified,with four main structural types.A total of 188 differentially expressed proteins were identified in the Poria triterpene group compared with the model group,of which 86 differentially expressed proteins were up-regulated and 102 differentially expressed proteins were down-regulated;GO database analysis showed that the differentially expressed proteins in the Poria triterpene group were mainly involved in the regulation of interleukin-1 production The KEGG database analysis showed that the differentially expressed proteins in the Poria triterpene group were involved in signaling pathways closely related to tumor,mainly MAPK,Apoptosis,mTOR,Wnt and p53 pathways,etc.The genes coding for the seven representative differential proteins were validated at the mRNA level by RT-qPCR.Conclusion The pharmacodynamic study found that Poria triterpenes had tumor suppressive effect on H22 ascites tumor mice,then by proteomics found Poria triterpenes group ascites H22 cell protein compared to the model group changed significantly,the study thus showed that Poria triterpenes for mice ascites tumor mechanism of tumor suppressive effect mainly involves apoptosis,inflammatory response and immune process.

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.