Objective: To investigate the barrier membrane fixation performance and enhanced guided bone regeneration (GBR) capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures. Methods: M2NP@BGN (methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle), a thermosensitive adhesive, was synthesized via free radical polymerization by compositing methoxyethyl acrylate, N-isopropylacrylamide, and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle (BGN). The successful fabrication of basic adhesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The thermosensitive adhesive M2NP@BGN (BGN concentration of 1 mg/mL) was characterized by scanning electron microscopy and a rheometer. By adjusting the BGN concentration (0.1 mg/mL, 0.5 mg/mL, 1 mg/mL, and 2 mg/mL), the adhesive and mechanical strengths were investigated with a universal testing machine. Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal formulation. The optimal material’s extract was co-cultured with mouse bone marrow mesenchymal stem cells, and its osteogenic activity was examined in vitro by quantitative real-time PCR, alkaline phosphatase, and alizarin red S staining. The rat mandibular defect model was established, filled with bone graft, and divided into 3 groups based on membrane fixation method: M2NP@BGN (BGN concentration of 1 mg/mL) fixation group (M2NP@BGN), titanium nail fixation group (Nail), and unfixed control group (Negative). Bone regeneration was analyzed after 8 weeks by micro computed tomography and histological staining. Results: M2NP@BGN (BGN concentration of 1 mg/mL) was successfully synthesized and demonstrated rapid gelation under warm, humid conditions. The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength (P < 0.001) and significantly enhanced mechanical strength (P < 0.001) under 37℃ wet conditions. All formulations showed excellent biocompatibility, with cell viability > 80% and hemolysis ratio < 5%. M2NP@BGN (BGN concentration of 1 mg/mL) significantly upregulated the expression of Runx2 and Col I (P < 0.001) and enhanced the activity of osteogenic differentiation markers (P < 0.05). In the animal model, the M2NP@BGN group (BGN concentration of 1 mg/mL) achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups (P < 0.05). Conclusion M2NP@BGN (BGN concentration of 1 mg/mL) combines excellent wet adhesion with potent osteogenic activity, enhances the bone augmentation efficacy of membranes, and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.

Objective To summarize the clinical features and treatment strategies of acute mercury poisoning caused by intramuscular injection of metallic mercury. Methods The clinical data of a patient with acute mercury poisoning following intramuscular injection of metallic mercury were collected, and a retrospective analysis of the diagnosis and treatment process was conducted. Results The patient was a 14-year-old boy who self-injected 20 g of metallic mercury into the left upper arm muscle. Clinical manifestations included fever, chest tightness, cough, and a painful mass at the injection site. Laboratory tests of the patient indicated that blood mercury level was 4.160 μmol/L, urinary mercury level was 6 545.50 μg/g creatinine, urinary retinol-binding protein was 6 556 μg/L, urinary β₂-microglobulin was 8 726.48 μg/g creatinine, and urinary α1-microglobulin was 41.60 mg/L at day 11 after injection. Thoracoabdominal imaging revealed mercury deposition in the lungs, heart, liver, kidneys, and other organs. The patient's clinical symptoms were markedly relieved after one course of treatment with sodium dimercaptopropanesulfonate for mercury chelation. Subsequent treatment included continued mercury chelation therapy, debridement of muscle tissue at the injection site, removal of retained foreign bodies, and other supportive measures. Reexamination showed a blood mercury level of 2.810 μmol/L and urinary mercury level of 5 280 μg/L at day 127 after injection. Conclusion The clinical manifestations of intramuscular injection of metallic mercury poisoning differ from those of occupational mercury poisoning. Debridement of the injection site combined with sodium dimercaptopropanesulfonate chelation therapy can alleviate systemic symptoms and reduce mercury levels in such patients.

AIM: To explore the risk factors of macular edema in patients with diabetes cataract after surgery, and provide reference for postoperative prevention and treatment.METHODS: A total of 55 diabetes cataract patients(55 eyes)with macular edema after phacoemulsification surgery at the ophthalmology department of Jiaozhou Central Hospital of Qingdao from January 2022 to January 2024 were selected as edema group. In addition, 59 patients(59 eyes)with diabetes cataract who received the same surgical treatment but did not develop macular edema were treated as control group, and the relationship between interferon-induced protein-10(IP-10), macrophage chemotactic protein-1(MCP-1), vascular endothelial growth factor(VEGF)and postoperative macular edema was analyzed.RESULTS:Age, diabetes course, best corrected visual acuity(BCVA), glycated hemoglobin(HbA1c), creatinine, levels of IP-10, MCP-1 and VEGF in aqueous humor in the edema group were higher than those in the control group(all P<0.05). The risk factors for postoperative macular edema in patients with diabetes cataract were prolonged duration of diabetes, BCVA, increased HbA1c, increased creatinine and IP-10 in aqueous fluid, increased MCP-1 and increased VEGF(all P<0.05).CONCLUSION:Macular edema after surgical treatment in diabetes cataract patients is associated with prolonged duration of diabetes, BCVA, HbA1c, creatinine, IP-10, MCP-1, and VEGF, and clinical interventions should be given in advance.

Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic on the rejection of mouse heart allograft. Methods BALB/c mice (donors) were used to transplant skin onto C57BL/6 mice (recipients). Four weeks later, memory CD4⁺ T cells (CD4⁺Tm) were isolated from the recipient mice's spleens. Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4⁺Tm, and the EdU method was used to detect the effect of Stattic on CD4⁺Tm cell proliferation. A C57BL/6 mouse heart transplant (HTx) model was constructed, and the experiment was divided into four groups: Non-HTx group, HTx group, Tm/HTx group, and Tm/HTx+Stattic group. The survival of heart allografts in mice was observed daily. Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-10, and transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) in the heart allografts. Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ, IL-2, IL-10, and TGF-β1 in the serum. Flow cytometry was used to detect the levels of CD4⁺Tm (CD4⁺CD44⁺CD62L⁺) in splenic lymphocytes. And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts. Results When the concentration of Stattic exceeded 2.5 μmol/L, it could inhibit the proliferation of CD4⁺Tm cells. Compared with the HTx group, the Tm/HTx group showed shorter survival time of heart grafts, more severe histopathological damage, increased serum IFN-γ and IL-2 levels, decreased IL-10 and TGF-β1 levels, increased relative expression of IFN-γ and IL-2 mRNA, decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, increased proportion of CD4⁺Tm in splenic lymphocytes, and increased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Compared with the Tm/HTx group, the Tm/HTx+Stattic group showed longer survival time of heart grafts, less severe histopathological damage, decreased serum IFN-γ and IL-2 levels, increased IL-10 and TGF-β1 levels, decreased relative expression of IFN-γ and IL-2 mRNA, increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, decreased proportion of CD4⁺Tm in splenic lymphocytes, and decreased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Conclusions Stattic may prolong the survival time of mouse heart allografts, and its mechanism may be related to the inhibition of CD4⁺Tm- mediated acute rejection.

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant