Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry* ; Sesquiterpenes/chemical synthesis* ; Molecular Structure ; Humans ; Liver Cirrhosis/genetics* ; Biomimetics ; Plant Extracts/pharmacology*

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF）， and to construct a risk scoring table that can accurately predict the prognosis of patients in the early stage. MethodsA retrospective analysis was performed for the clinical data of 502 patients with ACLF who were admitted to Tangdu Hospital， Air Force Medical University， from January 1， 2010 to December 31， 2020 （training set）， and the influencing factors for 28-day mortality rate were identified. The 69 ACLF patients who were admitted to Tangdu Hospital， Air Force Medical University， from January 1 to December 31， 2021 were enrolled as the validation set. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A univariate Cox regression analysis was used to obtain the early warning indicators associated with the 28-day prognosis of ACLF patients， and variance inflation factors were used to assess multicollinearity among predictors； a multivariate Cox regression analysis was used to construct a risk model for ACLF prognosis （mortality）. A risk scoring table for ACLF prognosis （mortality） was developed based on regression coefficients （β） from the model equation and weight assignments in the nomogram. Internal validation and comparison were performed for the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models （Child-Turcotte-Pugh ［CTP］ score， Model for End-Stage Liver Disease ［MELD］ score， MELD combined with serum sodium concentration ［MELD-Na］ score， and integrated MELD ［iMELD］ score） in the training set， while external validation and comprehensive evaluation of the scoring table and the other scoring models were performed in the validation set. The Nagelkerke’s R² test and the Hosmer-Lemeshow test were used to assess the degree of fitting of the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models， and fitting curves were plotted. C-index was used to assess the discriminatory ability of the scoring table for ACLF prognosis （mortality） and the other scoring models， and the Z-test was used for comparison of C-index between different models. The decision curve analysis was used to compare the clinical benefits of the scoring table for ACLF prognosis （mortality） and the other scoring models. ResultsThe multivariate Cox regression analysis showed that age （hazard ratio ［HR］=1.027， 95% confidence interval ［CI］： 1.015 — 1.039， P<0.001）， hepatic encephalopathy grade （grade 1： HR=2.928， 95%CI： 1.463 — 5.858， P=0.002； grade 2： HR=3.811， 95%CI： 2.078 — 6.988， P<0.001； grade 3： HR=3.916， 95%CI： 1.917 — 8.001， P<0.001； grade 4： HR=6.966， 95%CI： 4.559 — 10.644， P<0.001）， an increase in total bilirubin （TBil） by ≥17.1 μmol/L per day （HR=1.771， 95%CI： 1.248 — 2.513， P=0.001）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， neutrophil count （HR=1.092， 95%CI： 1.060 — 1.126， P<0.001）， and international normalized ratio （HR=1.298， 95%CI： 1.187 — 1.418， P<0.001） were independent risk factors associated with the 28-day mortality rate of ACLF patients， and a risk scoring table was constructed for ACLF prognosis （mortality）. The Nagelkerke’s R² test showed that the risk scoring table for ACLF prognosis （mortality） had an R² value of 0.599 in the training set and 0.722 in the validation set， which were higher than the R² values of CTP， MELD， MELD-Na， and iMELD scores. The Hosmer-Lemeshow test showed that the risk scoring table for ACLF prognosis （mortality） had a P value of 0.280 in the training set and 0.788 in the validation set. The C-index analysis showed that the scoring table had a higher C-index than the other scoring models in the validation set （all P<0.001）， as well as a higher C-index than CTP score in the training set （P<0.001）. The decision curve analysis showed that the risk scoring table for ACLF prognosis （mortality） had higher clinical net benefits than the other scoring models. ConclusionCompared with other scoring models currently used in clinical practice， the novel risk scoring table for ACLF prognosis （mortality） constructed based on the six predictive factors of age， hepatic encephalopathy grade， an increase in TBil by ≥17.1 μmol/L per day， creatinine， neutrophil count， and international normalized ratio has a relatively high value in predicting the 28-day prognosis of ACLF patients.

Objective:To investigate the differential responses of the endoplasmic reticulum stress-to-apoptosis cascade induced by proton ultra-high dose rate (FLASH) irradiation between lung epithelial and lung cancer cells.Methods:Human lung epithelial cells (KT) and lung adenocarcinoma cells (A549) were irradiated with protons, and divided into Ctrl, CONV and FLASH groups. Survival curves were generated using colony formation assay. Protein and mRNA expressions of the endoplasmic reticulum (ER) stress and apoptosis regulators were assessed via Western blot and RT-qPCR. The concentration of IL-6 secreted into the culture supernatant was determined by enzyme-linked immunosorbent assay(ELISA).Results:In KT cells, compared to the CONV group, FLASH irradiation resulted in a significantly higher survival fraction ( P<0.05), increased GRP78 protein expression ( t= 7.52, P < 0.05) and UPR-related genes PERK, ATF4, and CHOP. In A549, the cell survival rate did not differ significantly between the CONV and FLASH groups ( P > 0.05). UPR pathway was not activated in either group. However, both CONV and FLASH irradiation significantly promoted secretion of IL-6 ( t=4.31, 4.47, P<0.05), while no difference was identified between two groups. In KT, both irradiation promoted secretion of IL-6 ( t=7.43, 3.07, P<0.05) while IL-6 concentration in FLASH group was significantly lower than that in CONV group ( t=7.63, P<0.05). Additionally, a pro-apoptotic propensity in KT cells following FLASH irradiation and in A549 cells following both FLASH and CONV irradiation was identified. Conclusions:In KT cells, FLASH irradiation cleared misfolded proteins through activating UPR pathway, promoted apoptosis of damaged cells, suppressed IL-6 secretion to attenuate inflammatory injury, and ultimately enhanced cell survival. Furthermore, proton FLASH irradiation bypasses ER stress activation in A549 cells, instead directly priming an apoptotic disposition with concomitant IL-6 hypersecretion. This paracrine damage amplification cascade potentiates radiation-induced tumoricidal efficacy through sustained cytotoxic microenvironment remodeling.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To investigate the risk factors and their predictive efficacy for postoperative premature epiphyseal closure in pediatric patients with distal tibial epiphyseal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 216 pediatric patients with distal tibial epiphyseal fractures admitted to Zhengzhou Orthopedics Hospital from January 2018 to December 2023, including 136 males and 80 females, aged 2-16 years [11.8(9.8, 13.3)years]. Among them, 112 patients were affected on the left side and 104 on the right. According to the Salter-Harris fracture classification, the fracture was classified as type I in 14 patients, type II in 97, type III in 38, type IV in 64 and type VI in 3. According to the presence of premature epiphyseal closure after surgery, the patients were divided into premature epiphyseal closure group ( n=38) and normal epiphyseal group ( n=178). Age, gender, body mass index (BMI), injury mechanism, side of injury, Salter-Harris classification of fracture, initial displacement distance of the fracture end, medial malleolar involvement by the fracture line surgical fixation method, operation duration, reduction method, and reduction quality were recorded in the two groups. Univariate analysis and binary Logistic regression analysis were used to evaluate and determine the independent risk factors for postoperative premature physeal closure in pediatric patients with distal tibial epiphyseal fracture. The receiver operating characteristic (ROC) curve was plotted and area under the curve (AUC) was calculated to evaluate the predictive efficacy of each risk factor for the occurrence of premature physeal closure in pediatric patients with distal tibial epiphyseal fractures. Results:Univariate analysis showed the occurrence of postoperative premature epiphyseal closure of the distal tibia was associated with age, Salter-Harris fracture classification, medial malleolar involvement by the fracture line, surgical fixation method, reduction method, and reduction quality ( P<0.05), while it was not correlated with gender, BMI, injury mechanism, side of injury, initial displacement distance of the fracture end, and operation duration ( P>0.05). Multivariate binary Logistic regression analysis showed that medial malleolar involvement by the fracture line ( OR=0.18, 95% CI 0.04, 0.76, P<0.05) and reduction quality ( OR=43.18,95% CI 10.71, 174.05, P<0.01) were significantly correlated with the occurrence of postoperative premature epiphyseal closure of the distal tibia. The results of ROC curve analysis showed that medial malleolar involvement by the fracture line had limited predictive efficiency (AUC=0.53, 95% CI 0.43, 0.63), reduction quality had moderate predictive efficacy (AUC=0.81, 95% CI 0.72, 0.91), while their combination demonstrated even higher predictive efficacy (AUC=0.83, 95% CI 0.74, 0.91). Conclusions:Medial malleolar involvement by the fracture line and reduction quality are independent risk factors for postoperative premature epiphyseal closure in pediatric patients with distal tibial epiphyseal fractures. Reduction quality demonstrates good predictive efficacy, while medial malleolar involvement by the fracture line shows limited predictive value. The combination of both factors achieves even better predictive performance.

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Surface plasmon resonance （SPR） sensor is an optical detection technique enables real-time and dynamic monitoring of biological samples. SPR-based biosensors have remarkable characteristics such as label-free detection and high sensitivity, making them important tools for studying molecular interactions. The recognition element, which plays a critical role in SPR sensors,which could specifically identify and capture of target analytes, closely influencing the selectivity performance of the sensor. The progress on SPR sensors in pharmaceutical research were reviewed, which focused on the application of recognition elements such as antibodies, aptamers, molecularly imprinted polymers, and metal nanoparticles.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

The National Institute on Aging-Alzheimer's Association(NIA-AA)released the"Revised criteria for diagnosis and staging of Alzheimer's disease"in 2024,representing a significant update following the 2011 and 2018 frameworks.This new standard aims to advance Alzheimer's disease diagnosis and treatment from a"clinical-pathological"model to a"precision biology"era,improving early diagnosis rates and guiding precise therapeutic interventions.Nuclear medicine molecular imaging plays an irreplaceable role in Alzheimer's disease diagnosis and staging,with key updates in the 2024 standard being the replacement of traditional clinical diagnosis with biological definitions and the hierarchical classification of biomarkers.This article focuses on interpreting the core positioning and clinical application value of multimodal imaging technologies within the new standard framework,particularly the critical roles of amyloid β-protein PET and tau PET in early diagnosis,biological staging and treatment monitoring of Alzheimer's disease,aiming to provide guidance for clinical practice.

In 2025,the Response Assessment in Neuro-Oncology(RANO)working group and the European Association for Neuro-Oncology jointly released the updated guidelines for the clinical use of PET imaging in gliomas.Building upon the methodological framework established in the 2024 PET RANO 1.0 criteria,the new guidelines systematically integrate clinical evidence for amino acid PET and achieve alignment with MRI RANO 2.0 in imaging assessment logic,marking a paradigm shift of amino acid PET from a research tool to a clinical decision-making tool.This article provides a comprehensive analysis of key updates in the guidelines and evaluates the application value and recommendation levels of amino acid PET across critical clinical scenarios.Furthermore,it emphasizes the advantages of integrated PET/MR imaging in multimodal information integration for glioma management.