BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

ObjectiveTo investigate the role of Ras-GTPase-activating protein SH3 domain-binding protein 2 （G3BP2） in regulating the activation， proliferation， and migration of hepatic stellate cells （HSCs）. MethodsThe mouse HSCs （JS-1 cell line） were treated with 5 μg/L transforming growth factor-beta 1（TGF-β1） for 24 hours to establish an HSC activation and proliferation model. A G3BP2 knockdown system was constructed using siRNA interference technology. The experiment was divided into four groups： Control， TGF-β1 treatment， TGF-β1+si-NC， and TGF-β1+ G3BP2-siRNA. The expression levels of key fibrosis indicators， including type I collagen （Collagen I）， α-smooth muscle actin （α-SMA）， and G3BP2， were detected by Western blot and RT-qPCR. Cell proliferation activity was assessed using the CCK-8 proliferation assay kit and EdU fluorescence labeling technology. Cell migration ability was analyzed by scratch wound healing assay and Transwell migration assay. The formation level of stress granules was quantified by immunofluorescence microscopy to investigate the effects of G3BP2 on stress granule formation in activated HSCs. ResultsStimulation with TGF-β1 upregulated the expression of G3BP2 in JS-1 cells （RT-qPCR： P0.000 1； Western blot： P0.000 1）， while a downward trend in its expression was observed in the G3BP2‑silenced group （RT-qPCR： P0.01； Western blot： P0.000 1）. Compared with the control group， the TGF-β1 group exhibited increased protein expression levels of α-SMA and Collagen I （RT-qPCR： both P0.01； Western blot： P0.01 and P0.05， respectively）， concomitant with an increased number of stress granules and enhanced cell proliferation and migration capacity （all P0.001）. The experimental results demonstrated that G3BP2 knockout effectively reversed the aforementioned phenotypes， with the G3BP2-silenced group showing reduced expression of fibrotic markers （all P0.01）， decreased stress granule formation （P0.01）， and reduced cell proliferation and migration capacity （all P0.05）， compared to the negative control group. ConclusionG3BP2 enhances the activation， proliferation， and migration of HSCs by promoting the formation of stress granules， thereby accelerating the pathological progression of liver fibrosis. This suggests that stress granules may serve as important regulators in controlling the activation， proliferation， and migration of HSCs.

Background: and Purpose Accurately predicting long-term functional outcomes of basilar artery occlusion (BAO) remains challenging. We compared the predictive performance of the baseline, 24-hour, and 72-hour National Institutes of Health Stroke Scale (NIHSS) scores for 90-day BAO functional outcomes using the Acute Basilar Artery Occlusion: Endovascular Thrombectomy versus Standard Medical Treatment (ATTENTION) trial data. We identified the optimal assessment time point, determined treatment-specific NIHSS cutoff values, and explored the role of early neurological function in treatment effects. Methods: This retrospective post hoc analysis included 324 patients with acute BAO with baseline NIHSS scores ≥10 and complete NIHSS assessments at each time point. The primary outcome was a favorable 90-day functional outcome (modified Rankin Scale score, 0–3). Receiver operating characteristic curve analysis was used to assess the predictive ability of NIHSS scores. The optimal 72-hour NIHSS predictive cutoff values were determined for the endovascular treatment (EVT) and best medical management (BMM) subgroups. Results: The 72-hour NIHSS score showed the highest predictive accuracy for the primary outcome (area under the receiver operating characteristic curve [AUC]: 0.954), outperforming the 24-hour (AUC: 0.903) and baseline (AUC: 0.688) scores; its optimal predictive cut-off value was ≤11 in the EVT group (sensitivity: 85.6%, specificity: 92.9%, positive predictive value [PPV]: 91.8%, negative predictive value [NPV]: 87.4%) and ≤9 in the BMM group (sensitivity: 84.6%, specificity: 95.1%, PPV: 84.6%, NPV: 95.1%). Conclusions The 72-hour NIHSS score outperformed the baseline and 24-hour scores in predicting 90-day functional outcomes and mediating the effects of EVT. Treatment-specific 72-hour NIHSS cut-off values may guide early risk stratification and prognostic assessments.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

OBJECTIVE To identify the active components of Desmodium styracifolium （Osb.） Merr. extract （DME） against cholestatic liver injury （CLI）， and to verify its target and molecular mechanism， so as to provide scientific evidence for the clinical application of D.styracifolium （Osb.） Merr. and the development of new hepatoprotective agents.METHODS High-performance liquid chromatography was applied to establish fingerprints of 19 batches of DME， followed by similarity evaluation and identification of common peaks. An in vitro CLI model was constructed by lithocholic acid （LCA）-induced injury in HepG2 cells to evaluate the in vitro protective effect of DME against CLI. Spearman correlation analysis， grey relational analysis and partial least-squares regression analysis were adopted to investigate the spectrum-effect relationship of DME against CLI and preliminarily screen the core active components. Molecular docking and surface plasmon resonance technology were used to predict and verify the binding capacity between core active components and farnesoid X receptor （FXR）. qRT-PCR， Western blot and immunofluorescence staining tests were performed to validate the influences of core active components on the expression of molecules related to FXR/bile salt export pump （BSEP） pathway in CLI model cells.RESULTS A total of 12 common peaks were calibrated in the fingerprints of 19 batches of DME， and the similarity values were all above 0.990. Four common peaks were identified， namely peak 6 （schaftoside）， peak 7 （isoorientin）， peak 11 （isoschaftoside） and peak 12 （isovitexin）. DME at 80 μg/mL exerted the optimal protective effect on CLI-model cells， and the cell viability reached （75.66±4.60）% after 24 h of treatment. Spectrum-effect analysis revealed that schaftoside possessed the strongest correlation with the anti-CLI activity of DME and served as the core active component. Target prediction and validation results showed that the binding energy between schaftoside and FXR was －8.1 kcal/mol， and the equilibrium dissociation constant was 27.3 μmol/L. Mechanistic experiments demonstrated that 100 μmol/L schaftoside significantly elevated the expression levels of FXR and BSEP， and mRNA of their encoded genes Nr1h4 ， Abcb11 in CLI-model cells （ P ＜0.05）.CONCLUSIONS Schaftoside may be the core active component of DME against CLI， and its mechanism may be related to the activation of FXR/BSEP pathway.

Objective:To investigate the efficacy of enteral nutrition combined with trocar puncture with a sump drain in the treatment of Crohn's disease(CD)complicated by intra-abdominal abscess.Methods:A descriptive case series study was conducted.Clinical data of CD patients with intra-abdominal abscess who received enteral nutrition and trocar puncture with a sump drain at the Intestinal Fistula and Intra-abdominal Infection Center of Nanjing BenQ Hospital between June 2018 and December 2022 were retrospectively collected.Laboratory parameters,including white blood cell(WBC)count,C-reactive protein(CRP),and procalcitonin(PCT),were recorded at baseline(pre-puncture)and on days 1,3,and 7 post-puncture.Changes in clinical indicators before and after intervention were compared.Results:All 19 CD patients with intra-abdominal abscess successfully underwent CT-guided trocar puncture with a sump drain,with fistulography confirming the presence of intestinal fistula.No post-procedural complications,including puncture site infection,new-onset intestinal fistula or intra-abdominal hemorrhage,were observed.The median treatment duration was 58.3 days(range:14～300 days).10 patients achieved spontaneous healing while 9 eventually underwent surgical intervention for unresolved fistulas.Post-puncture WBC levels decreased significantly on days 1,3,and 7 compared to baseline(P<0.05).Serum CRP levels increased markedly on day 1 post-puncture(P<0.05)but declined significantly by days 3 and 7(P<0.05).No statistically significant difference was observed in serum procalcitonin levels before and after puncture(P>0.05).Conclusion:The combination of enteral nutrition and trocar puncture with a sump drain is safe,feasible,and effective for managing CD complicated by intra-abdominal abscess.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.