OBJECTIVE: To propose a new protocol for personalized mandibular reconstruction assisted by three-dimensional (3D) retrieval model based on fully connected neural network (FCNN) and a database of mandibles, and to verify clinical feasibility of the protocol. METHODS: A database of mandibles of 300 normal northern Chinese Han people was established. On the basis of cephalometry, the mandible landmarks with good stability were further screened. Mandibular landmarks were selected and geometric features of the mandible were extracted. A 3D retrieval algorithm was developed, which could retrieve the mandible most similar to a given mandible from the database. A FCNN was built to train the algorithm to improve accuracy of the 3D retrieval model. Using Geomagic Control 2014 software, matching accuracy of the 3D retrieval model was based on aforementioned mandible database and algorithm. From December 2019 to March 2021, a total of 5 patients underwent personalized mandibular reconstruction assisted by a 3D retrieval model based on mandible database and FCNN in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The most similar mandible was retrieved from mandible database through 3D retrieval algorithm. It was used to restore the premorbid morphology of defect area and guide mandibular reconstruction. For the 5 patients, mandible was reconstructed with iliac flap. Virtual surgical plan was transformed using individual surgical guides. RESULTS: Through screening, mandibular landmarks with high reproducibility and stability were identified and composed of mandibular landmarker protocols. After training, the average deviation between most similar mandible retrieved from the 300-case mandible database through 3D retrieval model based on FCNN and given mandible was (1.77±0.44) mm. And the root-mean-square deviation between the most similar mandible retrieved from the database and given mandible was (2.58±0.86) mm. The mandibular reconstruction surgery was successful in all the 5 patients. Their facial symmetry and occlusion were restored. All the patients were satisfied with postoperative appearance. The mean deviation between postoperative mandible and preoperative design was (0.98±0.17) mm. The area with a deviation ≤1 mm accounted for 61.34%±14. 13%, ≤2 mm accounted for 83.82%±7.35%, and ≤3 mm accounted for 93.94%± 2.87%. CONCLUSION The personalized mandibular reconstruction assisted by 3D retrieval model based on the 300-case mandible database and FCNN is feasible clinically.
Humans ; Neural Networks, Computer ; Mandibular Reconstruction/methods* ; Mandible/diagnostic imaging* ; Imaging, Three-Dimensional/methods* ; Adult ; Databases, Factual ; Female ; Male ; Algorithms ; Middle Aged ; Cephalometry

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Pathogenesis of immune thrombocytopenia(ITP)is complex,with a high reoccurence rate after first-line treatment and limited efficacy of second-line treatment,especially in refractory ITP,for which there is a lack of effective treatment.In recent years,it has been found that impaired function of mesenchymal stem cells(MSCs)is also involved in pathogenesis of ITP in addition to humoral and cellular immunity.Exogenous infusion of MSCs or endogenous restoration of immunomodulatory function of MSCs is expected to be an effective treatment strategy for ITP.Therefore,this article reviews biological characteristics and immunomodulatory effects of MSCs and their research progress in ITP,with aim of providing new ideas for further elucidating pathogenesis and exploring effective treatment options of ITP.

Objective To investigate the capacity of low-intensity pulsed ultrasound(LIPUS)for promoting osteogenic differentiation of senescent bone marrow mesenchymal stem cell(BMMSC)in mice,also the potential mechanism of involving myocardin-related transcription factor-A(MRTF-A)during this process.Methods Five aged mice received LIPUS irradiation on the left femur for eight weeks.Micro CT and HE staining were employed to evaluate bone status of bilateral femur.Bone marrow cells were isolated from mouse long bones,BMMSC were cultured,and the cells were divided into H2O2+LIPUS group,H2O2 group and control group.Mouse BMMSC were subjected to H2O2 for 3 days,followed by reactive oxygen species fluorescence staining and senescence-associated β-galactosidase staining to assess cellular senescence.Immunofluorescence and phalloidin staining were performed to examine MRTF-A distribution and cytoskeletal status.Based on H2O2-induced senescence model,MRTF-A nuclear translocation inhibitor CCG-100602 was applied,and the cells were further divided into H2O2+CCG-100602+LIPUS group,H2O2+CCG-100602 group,H2O2+LIPUS group and H2O2 group.Immunofluorescence staining was used to assess MRTF-A distribution.Alkaline phosphatase(ALP)and alizarin red staining were conducted to evaluate osteogenic differentiation capacity.Results LIPUS resulted in increased trabecular bone in the left femur of aged mice compared to the right femur,with increased bone volume to total volume and trabecular number and decreased trabecular spacing(both P＜0.05).Compared with H2O2 group,H2O2+LIPUS group showed increased nuclear expression of MRTF-A and increased intracellular rigid actin filament density.The nuclear expression of MRTF-A in H2O2+CCG-100602+LIPUS group was significantly lower than that in H2O2+LIPUS group.Compared with the H2O2+CCG-100602+LIPUS group and H2O2 group,the ALP and alizarin red staining positive areas in H2O2+LIPUS group were significantly larger.Conclusion LIPUS could improve osteoporosis in aged mice.Nuclear translocation of MRTF-A was a key regulator to LIPUS for promoting osteogenic differentiation of senescent BMMSC.

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

The transformation of medical models and the growing demand for healthcare necessitate the establishment of one-stop multimorbidity management clinics within general practice departments of general hospitals to enhance clinical management of patients with multiple chronic conditions. This study employed SWOT analysis to evaluate the internal conditions (strengths and weaknesses) and external conditions (opportunities and threats) associated with establishing such clinics. The analysis revealed that the strengths of general practice departments in general hospitals for establishing a multimorbidity clinic include abundant medical resources, the comprehensive nature of general practice functions, and multidisciplinary collaboration. Opportunities are presented by public health needs, supportive government policies, and technological advancements. However, weaknesses include shortages of qualified human resources, the high complexity of patient management, increased medical costs, limitations in insurance reimbursement, and difficulties in performance evaluation. Threats encompass an underdeveloped general practitioner system, patients′ traditional healthcare-seeking habits, medico-legal and ethical challenges, and a lack of directly transferable experience. Based on this analysis, the paper proposes strategies and measures for developing multimorbidity clinics within general practice departments of general hospitals in China, aiming to provide a theoretical foundation for their promotion and development.

Objective·To establish a research framework for serotonylation of proteins and to provide a methodological basis for the identification of serotonylated proteins.Methods·The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of the transglutaminase 2(TGM2)gene,which encodes the key enzyme for serotonylation,and the solute carrier family 6(SLC6A4)gene,which encodes the serotonin transporter(SERT),in normal and pan-cancer tissues.5-Propargyltryptamide(5-PT),a serotonin derivative,was synthesized stepwise from serotonin hydrochloride,and its structure was characterized by the Fourier transform infrared spectroscopy(FT-IR),proton nuclear magnetic resonance(1H-NMR),carbon nuclear magnetic resonance(13C-NMR),and time-of-flight mass spectrometry(TOF-MS).The intracellular uptake of 5-PT in the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and bone marrow-derived macrophages(BMDMs),was detected by using flow cytometry.Click chemistry,co-immunoprecipitation,and mass spectrometry analysis techniques were employed to identify serotonylated proteins,and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results·Bioinformatics analysis indicated that TGM2 and SLC6A4 were widely expressed in various normal tissues and across pan-cancer tissues.The flow cytometry results showed that the synthesized 5-PT can be taken up into the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and BMDMs,via the SERT.Mass spectrometry analysis data showed that a significant amount of serotonylated proteins were enriched in various cells treated with 5-PT.KEGG enrichment analysis revealed that these proteins were involved in important pathways related to glycolysis and amino acid synthesis.Conclusion·By using the synthesized 5-PT,multiple serotonylated proteins are enriched in various cell types.A research system for identifying serotonylated proteins has been successfully established,providing a relatively simple and efficient method for studying protein serotonylation.

Objective In this paper,CiteSpace(V6.3.R1)was used to sort out and summarize the experimental study on the mechanism and development trend of acupuncture intervention in Alzheimer's disease(AD),so as to provide basis and suggestions for subsequent research.Methods Relevant literatures on the mechanism of acupuncture intervention in AD were retrieved from CNKI database from March 1997 to March 2024.CiteSpace(V6.3.R1)software was used to visually display keywords,draw corresponding maps,and discuss the hot spots of acupuncture intervention mechanism in AD.Results After screening,a total of 397 articles were included in this study.The mechanism of acupuncture intervention in AD mainly focuses on the regulation of synaptic plasticity,regulation of neurotransmitter release,regulation of neuroinflammation,regulation of apoptosis,influence on mitochondrial autophagy,anti-oxidative stress and so on.Conclusion Acupuncture intervention in AD has developed rapidly,involving Notch1/Hes signaling pathway,Shh signaling pathway,NF-κB signaling pathway,PI3K/Akt signaling pathway and other signaling pathways.The research heat of TCM acupuncture intervention in AD continues to rise,and various research teams have harvested rich research results,diversified research hotspots,and in-depth exploration of acupuncture treatment of AD has rich clinical value.

Objective This study aims to investigate the effects of acupuncture on the spatial learning and memory capacities,the morphological characteristics of hippocampal neurons,the components of extracellular matrix,as well as the structure of the blood-brain barrier in SAMP8 mice.Moreover,it endeavors to explore the underlying mechanism through which the"Tongdu Qishen"(activating governor vessel and awakening spirit)acupuncture method ameliorates the cognitive function and modulates cerebral blood flow in SAMP8 mice.Methods Twenty 6-month-old male SAMP8 mice were randomly allocated into a model group and an electroacupuncture group,with ten mice in each group.Additionally,ten homologous 6-month-old male SAMR1 mice were designated as the normal control group.In the electroacupuncture group,the acupoint"Renzhong"(GV 26)was punctured using a quick insertion technique,while"Baihui"(GV 20)and"Yintang"(EX-HN 3)were punctured via a transverse insertion method.Subsequently,the needle handles were connected to an electroacupuncture apparatus,which was set to operate with a dense-sparse wave at a frequency of 100 Hz/2 Hz and an electric current of 2 mA.Each session of acupuncture lasted for 20 minutes and was conducted once a day for a consecutive period of 28 days.The normal group,the model group,and the electroacupuncture group all underwent identical fixation and restraint procedures to ensure consistent experimental conditions.The Morris water maze was employed to evaluate the spatial learning and memory abilities of the mice.The Nissl staining technique was utilized to assess the alterations in hippocampal neurons of SAMP8 mice.The laser speckle imaging system was adopted to measure the cerebral blood flow of the mice in each group.Transmission electron microscopy was applied to observe the ultrastructure of the blood-brain barrier within the frontal cortex tissue of the SAMP8 mice's brains.The Western blotting method was used to detect the expressions of Collagen-Ⅳ and Fibronectin in the brain tissues of SAMP8 mice.Results In comparison with the model group,the"Tongdu Qishen"acupuncture method demonstrated a significant efficacy in improving the spatial learning and memory abilities of SAMP8 mice(P<0.05).It also effectively alleviated the degeneration of hippocampal neurons,remarkably increased the cerebral blood flow perfusion volume of SAMP8 mice(P<0.05),ameliorated the damage to the blood-brain barrier structure,significantly upregulated the content of Collagen-Ⅳ(P<0.05),and significantly downregulated the content of Fibronectin(P<0.0001).Conclusion The"Tongdu Qishen"acupuncture method is capable of favorably regulating the extracellular matrix of SAMP8 mice,thereby improving cerebral blood flow and ultimately enhancing their learning and memory abilities.