Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

Objective: To analyze the significance of serum free light chain (sFLC) for the prognosis of the patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical data of 621 NDMM patients in Changzheng Hospital from June 2010 to December 2016 was retrospectively analyzed. The serum free light chain levels were measured and the ratios of κ/λ chains were calculated. The significance of serum free light chain ratio (sFLCR) for the prognosis of NDMM patients was analyzed. Results: Among the 621 NDMM patients, 42 patients (6.8%) were in the normal free light chain ratio group (0.26≤sFLCR≤1.65), 247 patients (39.8%) were in the low free light chain ratio group (0.01＜sFLCR＜0.26 or 1.65＜sFLCR＜100), and 332 patients (53.5%) were in the high free light chain ratio group (sFLCR≤0.01 or sFLCR≥100). Compared with normal sFLCR group, the abnormal sFLCR group showed low level of hemoglobin; elevated levels of bone marrow plasma cells, serum creatinine and β 2 -MG, and more patients were in DS stage Ⅲ and ISS stage Ⅲ with high risks of cytogenetics(all P＜0.05). The overall survival (OS) in the normal sFLCR group was significantly better than the abnormol sFLCR groups (not reached vs 58.7 months, P=0.043). Compared with the patients with both high sFLCR and low risks of cytogenetics, the patients with high sFLCR and high risks of cytogenetics showed shorter overall survival time (median OS time was 41.6 months vs 61.4 months, P=0.015). Conclusion The NDMM patients with significantly abnormal sFLCR may indicate more tumor load and higher aggressive progression. sFLCR should be an independent prognostic indicator for the outcome of multiple myeloma. The patients with high sFLCR and cytogenetic abnormalities, have worse prognosis than the others.

Objective: To analyze and explore the clinical characteristics and prognosis of patients with "double hit" multiple myeloma (MM) . Methods: We retrospectively analyzed 89 MM patients in our department of Shanghai Changzheng Hospital from 2010-2016. All patients were assayed by fluorescence in situ hybridization (FISH) and TP53 gene sequencing, based on Dr. Walker BA proposed the "double hit" MM concept, and then the clinical features and prognosis were evaluated. Results: In the results, 15 (16.85%) cases harbored "double hit" showed the median PFS of 8.4 months and the median OS 22.2 months, which was significantly lower than non-"double hit" patients with median PFS 14.2 months and the median OS 39.2 months, respectively (P<0.05) . Multivariate analysis displayed that the "double hit" was an independent poor prognostic factor on PFS (HR=2.171, 95%CI 1.206-3.907, P=0.010) and OS (HR=4.106, 95%CI 2.116-7.969, P<0.001) . Moreover, "double hit" MM patients had the higher adverse prognosis risk, which showed the shorter median OS and PFS than stage III of R-ISS patients (PFS 8.4 vs 11.8 months; OS 22.2 vs 24.3 months, P<0.05, respectively) . Conclusion Patients with "double hit" MM have a very poor clinical prognosis. Prospective clinical studies are urgently needed to improve these extra high risk patients.

Objective: To evaluate the prognostic value of serum free light chain ratio (rFLC) and difference (dFLC) in patients with multiple myeloma (MM) . Methods: Clinical data of 479 cases of newly diagnosed MM patients with FLC test records referred to our hospital from January 2012 to March 2016 were collected. rFLC preferred cut-off values were selected as≤14.828,14.828-364.597, ≥364.597 according to the literatures. The dFLC was divided into ≤112.85,112.85-2891.83, ≥2891.83 mg/L three groups. The rFLC and dFLC values among the death, the non-death, the progress and the non-progress groups were compared by t test. The correlation analysis showed that the rFLC and dFLC values were related to the death or progression of the disease. Logistic regression was used to analyze the correlation between each factor and death or progression. Univariate survival analysis (PFS) and total survival (OS) were performed using Kaplan-Meier. Single-variable and multivariate prognostic analysis were performed using Cox model. Results: The cutoff values of rFLC less than 14.828 or dFLC less than or equal to 112.85 mg/L impacted most significant on OS and PFS of the patients (P<0.05) . Different rFLC cut-off values between two groups showed that when rFLC=14.828, OS was significantly better than the other two groups (NR vs 61 & 47 months, P=0.019) ; different dFLC cut-off values between two groups disclosed that PFS and OS were statistically significant when dFLC less than or equal to 112.85 mg/L compared with the other two groups (P<0.05) . The 4-year PFS/OS rates in the initial dFLC≤112.85 mg/L and rFLC≤14.828 groups was significantly higher than of the other two groups. Conclusion Different cutoff levels of rFLC and dFLC might have obviously effects on the prognoses of patients with newly diagnosed MM. The difference of survival prognosis would be more pronounced when rFLC≤14.828 or dFLC≤112.85 mg/L with lower risk of death and lower risk ratio, which might be ideal cutoff value for determining the prognosis of these patients.

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: In this study we retrospectively analyzed 158 Ph⁺ ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ²=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ²=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ²=7.908, P=0.005) . Conclusions Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph⁺ ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.

Objective: To evaluate the clinicopathologic features of Rosai-Dorfman disease (RDD) , and elucidate the potential pathogenesis by whole exome sequencing (WES) . Methods: Clinico-pathological data of 23 RDD patients diagnosed between 2010 and 2018 in Changhai hospital were reviewed, and 9 paraffin-embedded specimens were performed for WES. Results: The median age of 23 RDD patients was 47 (10-79) years. Of them, 19 cases had extranodal lesions, 3 had nodal lesions, and 1 had nodal and extranodal lesions coincidently. All patients received surgery for lesion resection. Histiocytosis in lymph node sinuses or in extranodal tissues accompanied by lymphocyte phagocytosis are typical pathological features of RDD. Immunohistochemical staining shows histocytes are positive for S100, CD68 and CDl63, and negative for CD1a. mTOR, KMT2D and NOTCH1 mutations were detected with WES in these cases. Conclusion Mutations in mTOR, KMT2D and NOTCH1 genes may be involved in the pathogenesis of RDD, and their clinical significance needs to be further studied.

Objective: To evaluate the prognostic value of serum free light chain ratio (rFLC) and difference (dFLC) in patients with multiple myeloma (MM) . Methods: Clinical data of 479 cases of newly diagnosed MM patients with FLC test records referred to our hospital from January 2012 to March 2016 were collected. rFLC preferred cut-off values were selected as≤14.828,14.828-364.597, ≥364.597 according to the literatures. The dFLC was divided into ≤112.85,112.85-2891.83, ≥2891.83 mg/L three groups. The rFLC and dFLC values among the death, the non-death, the progress and the non-progress groups were compared by t test. The correlation analysis showed that the rFLC and dFLC values were related to the death or progression of the disease. Logistic regression was used to analyze the correlation between each factor and death or progression. Univariate survival analysis (PFS) and total survival (OS) were performed using Kaplan-Meier. Single-variable and multivariate prognostic analysis were performed using Cox model. Results: The cutoff values of rFLC less than 14.828 or dFLC less than or equal to 112.85 mg/L impacted most significant on OS and PFS of the patients (P<0.05) . Different rFLC cut-off values between two groups showed that when rFLC=14.828, OS was significantly better than the other two groups (NR vs 61 & 47 months, P=0.019) ; different dFLC cut-off values between two groups disclosed that PFS and OS were statistically significant when dFLC less than or equal to 112.85 mg/L compared with the other two groups (P<0.05) . The 4-year PFS/OS rates in the initial dFLC≤112.85 mg/L and rFLC≤14.828 groups was significantly higher than of the other two groups. Conclusion: Different cutoff levels of rFLC and dFLC might have obviously effects on the prognoses of patients with newly diagnosed MM. The difference of survival prognosis would be more pronounced when rFLC≤14.828 or dFLC≤112.85 mg/L with lower risk of death and lower risk ratio, which might be ideal cutoff value for determining the prognosis of these patients.
Humans ; Immunoglobulin Light Chains ; Multiple Myeloma ; Multivariate Analysis ; Prognosis ; Survival Analysis

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide ; Dexamethasone ; Doxorubicin ; Humans ; Middle Aged ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Retrospective Studies ; Vincristine