Objective: To explore the feasibility, precision, and clinical value of a personalized primary repair approach centered on digital design, integrating 3D printing technology with multiple materials such as titanium mesh, polyetheretherketone (PEEK), and titanium plates, for complex craniofacial bone defects involving the skull, mandible, orbit, and zygoma resulting from traffic accidents, providing a reference for primary repair of clinically complex craniofacial bone defects. Methods: One patient who was admitted in September 2021 with multiple comminuted fractures of the right craniomaxillofacial region and large-area bone defects caused by a traffic accident was selected. Digital design was integrated throughout the entire repair process. First, preoperative computed tomography (CT) data were used for 3D reconstruction of the craniomaxillofacial region; then, based on the model, the anatomical contour of the healthy left side was reproduced via mirroring technology for the defects on the right side. A targeted repair plan was designed: 3D-printed PEEK material was used to reconstruct the right orbital floor and zygomaticomaxillary complex, a 0.6-mm-thick titanium mesh was adopted to repair the right skull defect, and a 2.0-mm-thick titanium plate was applied for rigid internal fixation of the mandibular fracture. A one-stage repair surgery was completed simultaneously. In addition, a literature review was conducted on studies related to the repair of complex combined craniomaxillofacial defects. Results: CT examination at 1 week postoperatively showed that the average fitting gap of the implants was 0.3 mm, and the symmetry difference of the facial contour was less than 5 mm. At 3 months postoperatively, the patient’s maximum mouth opening reached 38 mm, the occlusal relationship returned to normal, and the diplopia symptom completely disappeared. During the 6-month postoperative follow-up, no complications such as implant loosening, infection, or displacement occurred; the FACE-Q scale score was 91, indicating a high level of subjective patient satisfaction. The literature review indicated that digital design combined with 3D printing technology can significantly improve the accuracy of complex craniomaxillofacial bone defect reconstruction. PEEK material is suitable for the reconstruction of the orbital floor and zygomaticomaxillary complex. Titanium mesh and plates can ensure the stability of the reconstruction. Multi-materials combined reconstruction represents an important therapeutic strategy for such defects. Conclusion The individualized one-stage repair scheme, centered on digital design and combined with 3D printing technology and multi-materials (titanium mesh, PEEK, and titanium plates), can achieve precise anatomical reduction and simultaneous functional recovery for complex combined craniomaxillofacial bone defects caused by traffic accidents.

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

Objective To investigate the clinical effect and safety of bronchial arterial chemoembolization(BACE)combined with micro wave ablation(MW A)and immunotherapy in treating patients with advanced lung squamous cell carcinoma.Methods The clinical data of 68 patients with advanced lung squamous cell carcinoma,who were admitted to the North Jiangsu People's Hospital of China from June 2020 to June 2022 to receive treatment,were retrospectively analyzed.According to the therapeutic method,the patients were divided into control group(n=30,receiving BACE combined with immunotherapy)and observation group(n=38,receiving BACE followed by MW A,which was performed with CT-guided localization of the lung lesion,and immunotherapy in 3-5 days after BACE).Results The surgical success rate in both the 30 patients of the observation group and the 38 patients of the control group was 100％.After treatment,no surgery-related or chemoembolization-related serious complications occurred in both groups.In the control group and the observation group,the mean progression-free survival(PFS)was(5.70±1.61)months and(12.10±0.72)months respectively,the mean overall survival(OS)was(11.80±1.10)months and(13.00±1.13)months respectively.The PFS of the observation group was obviously longer than that of the control group(P＜0.05),and no statistically significant difference in OS existed between the two groups(P=0.255).Conclusion BACE combined with MW A and immunotherapy can effectively control the advanced lung squamous cell carcinoma,it has reliable short-term efficacy when compared with BACE plus immunotherapy,and it can inhibit tumor growth and prolong the PFS of patients,with a trend of extending OS and a satisfactory clinical safety.

Objective: To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis. Methods: Human hepatoma cell lines PLC/PRF/5 and Huh_7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating agent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh_7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK_8 kit. The cell death induced by ES + Cu2 + was detected by flow cytometry and the changes of ES + Cu2 + after pretreatment with copper chelating agent ATTM. The expression of Cuproptosis related proteins ATPase copper transporting beta (ATP7B) ,ferredoxin 1 (FDX1) , dihydrolipoamide s_acetyltransferase(DLAT) and superoxide dismutase 1 (SOD1) were detected by Western blot. The effect of ES + Cu2 + on cell proliferation and the reverse effect after ATTM pretreatment was detected by cell scratch assay. Results: The toxicity of ES + Cu2 + to human hepatocellular carcinoma cell lines PLC/PRF/5 and Huh_7 was significantly dose_dependent (P < 0. 05) . Compared with the control group , the combined application of ES and Cu2 + had a more significant inhibitory effect on hepatocellular carcinoma cells than ES or Cu2 + alone (P < 0. 05) , and copper chelating agent ATTM could reverse the inhibitory effect of ES + Cu2 + on hepatocellular carcinoma cells (P < 0. 05) . Flow cytometry results showed that compared with the control group , the proportion of cell death in PLC/PRF/5 and Huh_7 cells treated with ES + Cu2 + increased , while the proportion of cell death decreased after ATTM intervention (P < 0. 05) . The results of cell scratch test showed that the migration ability of PLC/PRF/5 and Huh_7 cells was decreased after ES + Cu2 + treatment , however, the addition of ATTM reversed the inhibitory effect of ES + Cu2 + on cell migration (P < 0. 05) . Compared with the control group , the expression levels of copper death related proteins ATP7B , FDX1 , DLAT and SOD1 decreased after ES + Cu2 + treatment , but the addition of ATTM reversed the expression trend of these proteins (P < 0. 05) . Conclusion The combination of ES and Cu2 + can effectively inhibit the proliferation and migration of PLC/PRF/5 and Huh_7 of hepatocellular carcinoma cells , and induce Cuproptosis , which provides a new strategy for the treatment of hepatocellular carcinoma.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

OBJECTIVE: To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. METHODS: A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072). RESULTS: The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c.2384G>T (p.Gly795Val) and c.2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+PM3+PP3+PP4; PM1+PM2_Supporting+PP3+PP4). CONCLUSION The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.
Humans ; Male ; Child ; ATP-Binding Cassette Transporters/genetics* ; Stargardt Disease/genetics* ; Heterozygote ; Mutation ; Exome Sequencing ; Macular Degeneration/congenital*

Objective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.