Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.

Objective:To analyze the results of prenatal diagnosis for fetuses with a high risk for sex chromosome aneuploidies (SCAs) indicated by non-invasive prenatal testing (NIPT), and to assess the influence of maternal chromosomal factors on the results of NIPT.Methods:A retrospective analysis was conducted on the clinical data of 454 pregnant women with a high risk for SCAs indicated by NIPT undergoing invasive prenatal diagnosis at the Medical Genetics Center of Northwest Women′s and Children′s Hospital from January 2022 to September 2024. The data has included prenatal diagnosis indications, results, pregnancy outcomes, and chromosomal results of the pregnant women. This study has been approved by the Ethics Committe of Northwest Women′s and Children′s Hospital(Ethics No.2024-132)Results:Among the 454 women (including 10 with twin pregnancy) with a high risk for SCAs indicated by NIPT, 149 (including 4 twin cases) were diagnosed with SCAs through invasive prenatal diagnosis. These had included 47, XXX (37 cases), 47, XXY (56 cases), 47, XYY (29 cases), 45, X (1 case), 48, XXYY (1 case), mosaicism (20 cases), sex chromosome structural abnormalities (6 cases), and small-scale pathogenic copy number variations (3 cases). 383 pregnant women (including 7 with twin pregnancy) had accepted chromosomal karyotyping analysis. In total 49 cases(including 1 twih case) of SCAs were detected. Among them, 41 cases were pregnant women with SCAs but normal fetal chromosomes, which yielded a false positive rate for NIPT caused by maternal factors by 10.7%. In addition, 9 cases (including 1 twin case) had SCAs in both the pregnant woman and the fetus. Among the 383 pregnant women, 129 cases (including 3 twin cases) of fetal SCAs were diagnosed, which yielded an overall positive predictive value (PPV) of NIPT for SCAs by 33.7% (129/383). With the 41 false positive cases caused by maternal SCAs excluded, the PPV of NIPT for SCAs will be increased to 37.7% (129/342). Among the 454 pregnant women, twin pregnancies have accounted for 2.2% (10/454). Among the confirmed cases of SCAs, twin cases accounted for 2.7% (4/149). Among the 383 pregnant women undergoing chromosomal karyotyping, twin cases accounted for 1.8% (7/383). Among the detected cases of chromosomal abnormalities, twin cases accounted for 2.0% (1/49). Among singleton pregnancies, the positive predictive value (PPV) of NIPT for sex chromosome aneuploidies (SCAs) was 32.7% (145/444), in twin pregnancies, the PPV was 40.0% (4/10).Conclusion:NIPT can improve the screening efficiency for SCAs, but its PPV is limited. Therefore, pregnant women with a high risk for SCAs indicated by NIPT need to undergo invasive prenatal diagnosis for a definite diagnosis, while the PPV in twin pregnancies may be higher than in singletons, this observation is limited by the small sample size of twins in our study. The study confirmed that chromosomal abnormalitpies in pregnant women can significantly affect the accuracy of NIPT in detecting fetal SCAs. Therefore, when NIPT indicates SCAs, it is recommended to simultaneously conduct chromosomal karyotyping for the pregnant women. The combined application of chromosomal karyotyping analysis, fluorescence in situ hybridization, and copy number variation detection techniques can significantly improve the diagnostic accuracy for SCAs, especially for the detection of mosaicisms.

Objective:To investigate the current status and challenges in legal compliance regarding the collection, utilization, sharing, cross-border transfer, and disposal of human genetic resources (HGR) in international collaboration agreements, and to explore key review points for medical institutions in international cooperation agreements to mitigate legal risks and ensure compliance in HGR-related global collaborations.Methods:We reviewed international collaborative research projects involving Peking University Cancer Hospital that were approved or filed on the National Health Commission (NHC) Administrative Service Platform between July 2019 and April 2025, analyzed the utilization of human genetic resources (HGR) materials and information in these studies, assessd compliance clauses in international agreements related to HGR management, identified gaps, and proposed actionable recommendations.Results:A total of 410 international cooperation projects on human genetic resources were analyzed, of which 302 cooperation agreements signed with sponsors stipulated that research should obtain administrative approval or complete filing for human genetic resources before implementation(73.7%). However, 113 agreements had errors in citing legal provisions or incomplete agreements. A mtotal of 385 studies involved human genetic resource materials, of which 277 agreed on the compliant use of biological samples, but mainly focused on the collection and testing process, with insufficient agreements on the disposal of remaining samples. Some agreements only stipulate that ″compliant collection and use of samples″ is the sole responsibility of medical institutions, ignoring the relevant responsibilities of the sponsor, and the risk allocation is unreasonable. 361 studies involved human genetic resources information, but only 72 explicitly agreed that China′s human genetic resources information should be collected, preserved, used and shared within the approved scope of human genetic resources (less than 20%).Conclusions:The expression of human genetic resources related content in most agreements is not standardized; The management agreement for human genetic resources materials is incomplete and does not cover the entire cycle of sample processing; The responsibilities that the applicant should bear in the cooperation are unclear; The management of human genetic resource information is easily overlooked. It is recommended that medical institutions closely monitor changes in relevant laws, regulations, and management methods, and update the corresponding clauses of the agreement in a timely manner, and improve the situations that should be submitted for administrative approval or filing in the agreement; All parties involved in the cooperation should make compliance commitments for human genetic resources; Clearly stipulate the full cycle management of human genetic resources materials; Pay attention to risk prevention and control in the management of human genetic resources information; Pay attention to the systematic coverage of intellectual property types and the operability of rights implementation in international cooperation.

Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

Objective:To explore the promotion effect on remineralization of demineralized dentin of urushiol primer applicated in acid-etch-rinse adhesives,and to clarify its impact on the longevity of dentin adhesion.Methods:Ninety-six freshly extracted,caries-free third molars were selected to prepare the dentin specimens.Following acid etching with 37％phosphoric acid gel,the specimens were randomly divided into blank control group,0.3％,0.7％,1.0％,and 1.5％urushiol groups,and positive control group(acetone solvent).The treated samples were placed in modified simulated body fluids for remineralization for 14 and 28 d.Attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR)was used to detect the relative mineralization mass of minerals in the dentinal tubules in various groups,and X-ray Diffractometery and Energy Dispersive spectrometer were used to analyze the dentin surface material compositions in various groups.Scanning electron microscope(SEM)was used to observe the surface morphology of the specimens in various groups,Vickers hardness tester was used to measure the microhardness of the dentin surface in various groups,and microtensile strength(μTBS)was used to examine the effect of the bond strengthes in various groups.Results:Compared with blank control group,the conversion rate of adhesive double bonds by primer in positive control group was decreased,but the difference was not significant(P＞0.05);but the conversion rates of adhesive double bonds by primer in 0.3％,0.7％,1.0％,and 1.5％urushiol groups were increased(P＜0.05).The SEM results revealed that at 14 and 28 d,compared with bland control group,a minimal membranous deposit in dentinal tubules was seen in positive control group,minimal mineralization displayed in 0.3％urushiol group,significant deposition of loose mineral particles with blocking the tubule orifices was found in 0.7％urushiol group,noticeable mineral precipitates exhibited in 1.0％urushiol group,and relatively empty dentinal tubules were seen in 1.5％urushiol group.The microhardness results showed that at 14 d after remineralization,compared with blank control group,the microhardness in positive control group showed no significant improvement(P＞0.05),while the differences in 0.3％,0.7％,1.0％and 1.5％urushiol groups were statistically significant(P＜0.05);at 14 d after remineralization compared with positive control group,the microhardness of dertin in 0.7％and 1.0％urushiol groups were increased(P＜0.05);at 28 d after remineralization,compared with blank control and postive control groups,the microhardness in urushiol groups were significantly increased(P＜0.05),espectially in 0.7％to 1.5％urushiol groups(P＜0.05).In the μTBS test,at 14 d after remineralization,compared with postive control group,theμTBS in 0.3％,0.7％,1.0％and 1.5％urushiol groups were increased(P＜0.05);at 28 d after remineralization,the μTBS in blank control group was the lowest;compared with blank control group,there was no significant difference in the μTBS in postive control group(P＞0.05);compared with positive control group,the μTBS in 0.3％,0.7％,1.0％,and 1.5％urushiol groups were increased(P＜0.05),espectially in 0.7％,1.0,and 1.5％urushiol groups(P＜0.05).Conclusion:Natural-derived urushiol,as a novel primer,can pretreat the demineralized dentin substrates,and facilitate collagen cross-linking within the dentin matrix;moreover,it leverages the phenolic hydroxyl groups within its structure to attact calcium and phosphate ions,envelope dentin collagen fibers to promote remineralization,in order to enhance the strength of the resin-dentin bonding interface.

Objective:To study the effect of angiopoietin-1(Ang-1)and tyrosine kinase receptor 2(Tie2)inhibitor on glucose transportation in the human umbilical vein endothelial cells(HUVECs)cultured under high glucose conditions,and to clarify its mechanism.Methods:The HUVECs were cultured in high glucose(30 mmol·L?1)in vitro and treated with 0,200,500,1 000,and 2 000 μg·L?1 Ang-1 and 0,2 500,5 000,and 7 500 nmol·L?1 Tie2 inhibitor;cell counting kit-8(CCK-8)method was used to detect the cell activity to screen the optimal concentrations of Ang-1 and Tie2 inhibitor.Glucose kit was used to detect the glucose level in the supernatant of the HUVECs after Ang-1 intervention.The HUVECs were randomly divided into blank control group(NG group),high glucose group(HG group),HG+Tie2 inhibitor group(HG+In-Tie2 group),HG+Ang-1 group,HG+Ang-1+Tie2 inhibitor group(HG+Ang-1+In-Tie2 group),and HG+Ang-1+phosphatidylinositol 3-kinase(PI3K)inhibitor group(HG+Ang-1+LY294002 group).5-Ethynyl-2'-deoxyuridine(EdU)method was used to detect the proliferation activities of the cells in various groups;YO-PRO-1/PI method was used to detect the apoptotic rates of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Ang-1 mRNA and Tie2 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Tie2,glucose transporter 1(GLUT1),and glucose transporter 4(GLUT4)proteins and the ratios of phosphorylated PI3K(p-PI3K)/PI3K and phosphorylated protein kinase B(p-AKT)/AKT in the cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μg·L?1 Ang-1 group,the activity of the HUVECs was significantly increased after treated with 200 μg·L?1 Ang-1 for 48 h(P<0.01);compared with 0 nmol·L?1 Tie2 inhibitor group,the activity of the HUVECs was significantly decreased after treated with 2 500、5 000 and 7 500 nmol·L?1 Tie2 inhibitor(P<0.01);the optimal concentrations of Ang-1 and Tie2 inhibitor were 200 μg·L?1 and 2 500 nmol·L?1,respectively.Compared with NG group,the glucose level in the supernatant of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the glucose level in the supernatant of the HUVECs in Ang-1 group was significantly decreased(P<0.01).The EdU assay results showed that compared with NG group,the proliferation activity of the HUVECs in HG group was significantly decreased(P<0.01);compared with HG group,the proliferation activity of the HUVECs in HG+In-Tie2 group was significantly decreased(P<0.01),and the proliferation activity of the HUVECs in HG+Ang-1 group was significantly increased(P<0.01);compared with HG+Ang-1 group,the proliferation activities of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).The YO-PRO-1/PI assay results showed that compared with NG group,the apoptotic rate of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the apoptotic rate of the HUVECs in HG+In-Tie2 group was significantly increased(P<0.01),and the apoptotic rate of the HUVECs in HG+Ang-1 group was significantly decreased(P<0.01);compared with HG+Ang-1 group,the apoptotic rates of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly increased(P<0.01).The RT-qPCR results showed that compared with NG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG group and HG+In-Tie2 group were significantly decreased(P<0.01);compared with HG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in HG+In-Tie2 group were significantly decreased(P<0.01),and the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1 group were significantly increased(P<0.05);compared with HG+Ang-1 group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with NG group,the expression level of Tie2 protein in the HUVECs in HG group was significantly decreased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly increased(P<0.01);compared with HG group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),the expression level of Tie2 protein in the HUVECs in HG+Ang-1 group was significantly increased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly decreased(P<0.01);compared with HG+Ang-1 group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Compared with NG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG group were significantly increased(P<0.01);compared with HG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),and the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1 group were significantly decreased(P<0.01);compared with HG+Ang-1 group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Conclusion:Ang-1 down-regulates the expressions of GLUT1 and GLUT4 in the HUVECs cultured under high glucose conditions;the binding of Ang-1 to Tie2 may down-regulate GLUT1 and GLUT4 via the PI3K/AKT signaling pathway to participate in the glucose transportation in the HUVECs cultured under high glucose conditions.

The pathogenesis and progression of myocardial fibrosis(MF)are modulated by diverse cytokines and signaling pathways.Studies in recent years have revealed an extremely close association between MF evolution and programmed cell death(PCD)modali-ties,including apoptosis,autophagy,pyroptosis,necrosis,ferroptosis,and cuproptosis.This article reviews the characteristics of MF and distinct PCD modalities,with particular emphasis on cutting-edge discoveries elucidating PCD in the field of MF,hoping to pro-vide a theoretical-level reference basis for the in-depth exploration and clinical intervention of MF.

Objective To explore the roles of transfer RNA-derived small RNAs(tsRNAs)in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.Methods The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center.The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas(TCGA)database(TCGA-LUAD).The target genes were predicted based on TRFtarget2.0 and tRFTar databases.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)database.In vitro cell proliferation,migration,and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results Compared with the normal tissues,tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues(log2FC=4.28,FDR＜0.05).High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival(HR=1.565,95％CI=1.142-2.145,P=0.005).And its overexpression promoted cell proliferation and migration(P＜0.001),and invasion(P=0.009)of A549 cells,and up-regulated COL1A1(P=0.002)and VCAN(P=0.022)significantly in the tRF-19-69M8LOJX overexpression cell model.Conclusion tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues.And its high expression is closely associated with poor prognosis.The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.