Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

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).

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To investigate the effects of Xuebijing injection on gut microbiota and intestinal mechanical barrier in mice with lipopolysaccharide (LPS)-induced sepsis, and analyze the potential mechanism by which Xuebijing injection protects gastrointestinal tract.Methods:Twenty-four healthy and clean grade male C57BL/6N mice were divided into four groups, control group, LPS group, LPS+ 5 μl/g Xuebijing injection group (5 μl/g Xuebijing injection group), and LPS+ 10 μl/g Xuebijing injection group (10 μl/g Xuebijing injection group), with six mice in each group. A mouse model of sepsis was established by intraperitoneal injection of mice with 10 μg/g LPS. At 0 and 12 h after successful modeling, the mice were intraperitoneally injected with 5 or 10 μl/g Xuebijing injection. Blood, ileum, and colon fecal samples were collected 12 h after the second administration. ELISA was used to detect the levels of diamine oxidase (DAO), D-blood lactic acid (D-Lac), TNF-α, and IL-6. HE staining was used to observe the local ileum damage, and Chiu′s score was used to evaluate the degree of intestinal tissue damage. Immunohistochemical staining and Western blot were used to detect the expression of Claudin-1, Occludin, and zona occludins-1(ZO-1) in ileum tissues, followed by semi quantitative analysis. One-way analysis of variance was used for intergroup comparisons, and LSD or Tamhane′s T2 test was used for pairwise comparisons based on the homogeneity of variance. The diversity and species composition of mouse fecal microbiota, and the differences among groups were analyzed using 16S rRNA sequencing.Results:The levels of DAO, D-Lac, TNF-α, and IL-6 in the LPS group were higher than those in the control group (all P<0.000 1). After the intervention with Xuebijing injection, the levels of DAO, D-Lac, TNF-α, and IL-6 decreased (all P<0.05) and showed no significant differences with those in the control group (all P>0.05). Besides, 10 μl/g Xuebijing injection was more effective than 5 μl/g Xuebijing injection in reducing the concentrations (all P<0.05). Chiu′s score was higher in the LPS group than in the control group and the 10 μl/g Xuebijing injection group (both P<0.05). Western blot showed that the expression levels of Occludin, Claudin-1, and ZO-1 in the LPS group were lower than those in the control group (all P<0.01), and Xuebijing injection intervention significantly increased the expression levels of these proteins in a dose-dependent manner as compared with the LPS group (all P<0.000 1). Apart from the expression level of ZO-1, which showed no significant difference between the two Xuebijing injection groups ( P>0.05), the results of immunohistochemical staining were consistent with those of Western blot. The 16S rRNA sequencing results showed that there were differences in the Alpha and Beta diversity indices, and the composition and structure of gut microbiota among the four groups. The structure of gut microbiota in the mice treated with Xuebijing injection was similar to that in the mice of the control group and it was in a dose-dependent manner. Wilcoxon rank sum test showed that there were statistically significant differences in six gut microbiota groups at the phylum level, and 32 gut microbiota groups at the genus level among the mice of four groups (all P<0.05). Conclusions:Xuebijing injection can provide protective effects on the gastrointestinal tract by protecting the structure of gut microbiota and intestinal barrier function, and the protective effect is somewhat correlated with the drug dosage.

Objective:To construct a full-length infectious clone of enterovirus D68（EV-D68）expressing enhanced green fluorescent protein（EGFP）by reverse genetics in order to provide an efficient tool for studying the biological characteristics and screening antiviral drugs for EV-D68.Methods:Gene synthesis and overlap PCR techniques were used to construct the full-length clone plasmid pUC57-EV-D68 of EV-D68. The full-length viral sequence was then transferred into the pCAGGS plasmid to obtain the pCAGGS-EV-D68 plasmid. The EGFP gene was amplified and inserted into the pCAGGS-EV-D68 plasmid to construct the pCAGGS-EGFP-EV-D68 plasmid. Then，the two constructed plasmids were transfected into human rhabdomyosarcoma（RD）cells to rescue recombinant viruses RV-EV-D68 and RV-EGFP-EV-D68. The rescued viruses were identified using PCR，Western blot，and immunofluorescence techniques. The antiviral effect of doxycycline was evaluated using the rescued RV-EGFP-EV-D68. Statistical analysis was performed using the two independent samples t-test. Results:The recombinant virus RV-EGFP-EV-D68 capable of expressing EGFP was successfully rescued. Even after 15 serial passages，the virus retained EGFP expression with no significant difference in viral titers compared to the parental virus，indicating its stable passage in RD cells. Besides，the rescued strains exhibited similar replication characteristics to the parental virus. While at 24 and 36 h after infection，the titers of the rescued strains were significantly lower than that of the parental strain（both P<0.05）. This study demonstrated that doxycycline significantly reduced the fluorescence intensity of RV-EGFP-EV-D68-infected RD cells（ P<0.01）. Meanwhile，a negative correlation was observed between the doxycycline concentration and the fluorescence intensity，indicating that the rescued virus could be used for antiviral drug evaluation. Conclusions:This study successfully constructs an infectious clone of EV-D68 expressing EGFP. The rescued recombinant virus RV-EGFP-EV-D68 has been verified to be applicable for the evaluation of antiviral drugs.

Objective To search,evaluate and integrate the evidence on enteral nutrition management based on intra-abdominal pressure(IAP)in ICU patients so as to provide an evidence-based basis for a standardised clinical enteral nutrition management for ICU patients with abdominal hypertension.Methods According to the"6S"model,the systematic searches were conducted on CNKI,VIP,SinoMed,Wanfang,Cochrane Library,Medive,UpToDate,International Guidelines Collaboration,Scottish Intercollegiate Guidelines,PubMed,Ovid,Web of Science,Embase,NICE,American Society for Parenteral Enteral Nutrition,World Association for Parenteral Syndromes,European Society of Critical Care,European Society of Clinical Nutrition and Metabolism on the grading of enteral nutrition based on intra-abdominal pressure classification,including guidelines,clinical decision-making,expert consensus,systematic evaluations,summaries of evidence,and original studies closely related to the topic of this study,with a search timeframe up to 31st October 2023.Evidence was extracted and synthesised from the literature that met the quality criteria,taking into account clinical professional judgement.Results A total of 23 articles were retrieved,including four guidelines,one evidence summary,one systematic evaluation,four expert consensuses,six randomized controlled trials,one case-control study and six quasi-experimental studies.Through strict quality evaluation,evidence extraction and summarisation,seven themes with 28 pieces of best evidence were extracted,with IAP grading as the main topic.The themes included definition and grading of abdominal hypertension,IAP monitoring,assessment of target feeding volume,IAP grades I-IV.Conclusion This study summarises the best evidence on graded enteral nutrition management for ICU patients based on IAP.This evidence provides an effective scientific basis on clinical decision-making for ICU professionals.It aims to manage the enteral nutrition for ICU patients with intra-abdominal hypertension using a scientific nursing method,thereby improving the quality of nursing care.

BACKGROUND:Relatively or absolutely active bone resorption function of osteoclasts is one of the causative factors of osteoporosis. Therefore,how to inhibit the formation of osteoclasts and reduce the bone resorption activity is a key element in the prevention and treatment of osteoporosis. Liquiritin,which is derived from licorice,plays a role in the clinical treatment of bone diseases,but there are fewer studies addressing the application of liquiritin in osteoporosis and the mechanism is unknown.OBJECTIVE:To confirm,through both in vivo and in vitro experiments,that liquiritin inhibits osteoclast differentiation and alleviates bone loss.METHODS:Cell counting kit-8 was used to detect whether Liquiritin exerts toxic or proliferative effects on mouse bone marrow-derived macrophages,and tartrate-resistant acid phosphatase staining was performed to observe the effect of liquiritin in inhibiting osteoclast differentiation. The affinity of liquiritin binding to proteins related to osteoclast differentiation was verified by network pharmacology. RT-PCR and western blot assays were performed to detect the inhibitory effects of liquiritin on osteoclast-specific protein and gene expression as well as relevant signaling pathways. Finally,the mitigating effect of liquiritin on bone loss was verified in the C57BL/6J mouse osteoporosis model.RESULTS AND CONCLUSION:Liquiritin,at concentrations of 20 μmol/L and below,could inhibit the formation and differentiation of osteoclasts. Concurrently,it exhibited a high affinity with osteoclast-specific proteins such as nuclear factor of activated T-cells 1,Cathepsin K,c-Fos,and matrix metalloproteinase 9,and reduced the relative expression levels of these genes and proteins. Liquiritin could also effectively lower the phosphorylation expression level of JNK in the MAPK signaling pathway at the 15th,30th,45th,and 60th minutes,and it could salvage the degradation of nuclear factor-κB inhibitor α in the nuclear factor-κB signaling pathway at the 60th minute. In vivo experiments demonstrated that liquiritin could mitigate bone loss caused by osteoclasts and improve parameters related to trabecular bone. To conclude,liquiritin possesses the capacity to inhibit osteoclast differentiation and alleviate bone loss,thereby exerting a protective role against osteoporosis.

BACKGROUND:Current strategies for the treatment of the corticospinal tract after spinal cord injury mainly focus on exercise rehabilitation,drug therapy,transcranial magnetoelectric stimulation,endogenous regulation such as transcription factors and specific signaling pathways.Among them,transcription factors and their specific signaling pathways are the key factors regulating the axonal regeneration of corticospinal tract after spinal cord injury.A large number of preclinical studies have confirmed that the synergy between transcription factors and their signaling pathways has a significant regulatory effect on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.Therefore,it has broad application prospects to explore new combination therapy strategies targeting transcription factors and specific signaling pathways for spinal cord injury.OBJECTIVE:To systematically summarize the regulatory effects of transcription factors and their signaling pathways on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury and the underlying molecular mechanisms,and explore the application of combined therapy strategies targeting transcription factors and signaling pathways in the neuroplasticity of the corticospinal tract after spinal cord injury,in order to provide a new combination strategy for the treatment of spinal cord injury.METHODS:The search terms included"spinal cord injury,axon regeneration,transcription factors,signaling pathway,corticospinal tract,central nervous system,synergistic system,neuroprotective system"in Chinese and English.A literature retrieval was conducted in WanFang,Web of Science,and PubMed for relevant literature published from database inception to September 2024.Finally,101 articles were included for analysis and summary.RESULTS AND CONCLUSION:(1)The article outlines the biological properties and intervention strategies for axonal regeneration of the corticospinal tract after spinal cord injury,analyses the reasons for focusing on the corticospinal tract after spinal cord injury,and elucidates the response and possibility of regeneration of the corticospinal tract after spinal cord injury.(2)In this study,the combined regulatory strategy of transcription factors centered on Krüppel-like factor 6,Krüppel-like factor 7,and neuronal restriction silencing factor can significantly promote the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.(3)The phosphatidylinositol 3-kinase-protein kinase B-rapamycin target protein signaling pathway and Wnt5a pathway are the classical signaling pathways fortranscription factors to regulate the axonal regeneration of corticospinal tract neurons,and the combined treatment strategy can effectively promote the axonal regeneration and functional reconstruction of corticospinal tract neurons after spinal cord injury.(4)This article discusses the combined treatment strategies of transcription factors and specific signaling pathways in a comprehensive and detailed manner,such as Krüppel-like factor 6 combined with signal transducer and activator of transcription 3,Krüppel-like factor 7 combined with SOX11 transcription factor,combined inhibition of phosphatase and tensin homologs and neuronal restriction silencing factor,etc.,to exert a synergistic effect and promote the axonal regeneration of corticospinal tract neurons after spinal cord injury,which are significantly better than those of single treatment.It can effectively improve functional recovery and provide a reference scheme for the future treatment of axonal regeneration of corticospinal tract neurons after spinal cord injury.However,the specific mechanism of the combination therapy still needs to be further studied,and the current combination strategy is only widely used in animal models but not in clinical practice.(5)The combined therapy strategy based on transcription factors and specific signaling pathways has a significant therapeutic effect on the axonal regeneration of corticospinal tract neurons after spinal cord injury,and it is necessary to further explore the molecular mechanism of joint regulation in the future,in order to provide an effective combined therapy strategy for the rehabilitation and functional reconstruction of spinal cord injury.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.