Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

PURPOSE: To analyze risk factors for severe trauma and establish a nomogram for early risk prediction, to improve the early identification of severe trauma. METHODS: This study was conducted on the patients treated in 81 trauma treatment institutions in Gansu province from 2020 to 2022. Patients were grouped by year, with 5364 patients from 2020 to 2021 as the training set and 1094 newly admitted patients in 2020 as the external validation set. Based on the injury severity score (ISS), patients in the training set were classified into 2 subgroups of the severe trauma group (n = 478, ISS scores ≥25) and the non-severe trauma group (n = 4886, ISS scores <25). Univariate and binary logistic regression analyses were employed to identify independent risk factors for severe trauma. Subsequently, a predictive model was developed using the R software environment. Furthermore, the model was subjected to internal and external validation via the Hosmer-Lemeshow test and receiver operating characteristic curve analysis. RESULTS: In total, 6458 trauma patients were included in this study. Initially, this study identified several independent risk factors for severe trauma, including multiple traumatic injuries (polytrauma), external hemorrhage, elevated shock index, elevated respiratory rate, decreased peripheral oxygen saturation, and decreased Glasgow coma scale score (all p < 0.05). For internal validation, the area under the receiver operating characteristic curve was 0.914, with the sensitivity and specificity of 88.4% and 87.6%, respectively; while for external validation, the area under the receiver operating characteristic curve was 0.936, with the sensitivity and specificity of 84.6% and 93.7%, respectively. In addition, a good model fitting was observed through the Hosmer-Lemeshow test and calibration curve analysis (p > 0.05). CONCLUSION This study establishes a nomogram for early risk prediction of severe trauma, which is suitable for primary healthcare institutions in underdeveloped western China. It facilitates early triage and quantitative assessment of trauma severity by clinicians prior to clinical interventions.
Humans ; Nomograms ; Male ; Female ; Wounds and Injuries/diagnosis* ; Risk Factors ; Middle Aged ; Adult ; Injury Severity Score ; Risk Assessment ; ROC Curve ; Aged ; Logistic Models ; China ; Glasgow Coma Scale

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

AIM:The aim of this study is to investigate the clinical utility of neutrophil gelatinase-associated lipocalin(NGAL)and other biomarkers in serum for patients with acute and chronic kidney injury.METHODS:A total of 171 patients with acute kidney injury(AKI)and 209 patients with chronic kidney disease(CKD)who sought medical care at the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou between January 2022 and July 2023 were in-cluded in this study.Data on potassium(K),sodium(Na),chloride(Cl),carbon dioxide(CO2),urea(Urea),and glu-cose(GLU)were collected from each group of participants.A total of 94 individuals who were deemed healthy and had un-dergone physical examinations within the same time frame were chosen as the control group.The serum NGAL levels of all three groups were measured using latex immunoturbidimetry.The diagnostic effectiveness of serum NGAL and other bio-markers in identifying acute and chronic kidney injury was analyzed.Multiple logistic regression equations were employed to examine the factors influencing the occurrence of AKI and CKD in patients.Additionally,receiver operating characteris-tic(ROC)curves were constructed to evaluate the clinical significance of these biomarkers in patients with kidney injury.RESULTS:Through bioinformatic analysis,it was suggested that NGAL may be a detection marker of kidney injury.Ac-cording to general data,in the AKI and the CKD groups,K,Na,CO2,Urea,GLU and NGAL levels were higher than those in the healthy control group(P＜0.05).Multivariate logistic regression equation analysis showed that Na,Urea,GLU and NGAL levels were all independent risk factors for AKI or CKD disease occurrence(P＜0.05).The ROC curve analysis showed that in the AKI group,the area under the curve(AUC)for Na,Urea,GLU and NGAL were 0.711,0.960,0.793 and 0.841,respectively(P＜0.01).In the CKD group,the AUC for Na,Urea,GLU and NGAL were 0.681,0.990,0.703 and 0.930,respectively(P＜0.01).The sensitivity and specificity of NGAL and Urea combined diagnosis for AKI were 81.9%and 61.1%,respectively,and those for CKD were 62.7%and 80.0%,respectively.CONCLUSION:Serum NGAL can serve as an indicator of acute and chronic kidney injury,and its combination with other biomarkers also has certain clinical application value in acute and chronic kidney injury.

Objective To assess the effectiveness of Healthcare Failure Mode and Effect Analysis(HFMEA)in the intravenous thrombolysis process for patients with Acute Ischemic Stroke(AIS).Methods The targeted and comprehensive emergency care plan was constructed using HFMEA methodology.This plan was then applied to optimize the intravenous thrombolysis process in the target hospitals.Key indicators were evaluated before and after the intervention using t-tests,chi-square tests,and non-parametric tests.Results After the implementation of HFMEA,the mean Risk Priority Number value for the intravenous thrombolysis process in AIS decreased compared to before implementation.Additionally,the rate of intravenous thrombolysis within 4.5 hours of onset increased to 54％.The HFMEA model management group showed an 8％improvement compared to the conventional management group.The median time between patient admission and the start of intravenous thrombolysis door to needle time(DNT)was shorter,hospitalisation costs were lower,and National Institutes of Health Stroke Scale scores were reduced at 1 and 2 weeks post-treatment,as well as at discharge.However,there was no significant difference in the number of hospital days between the two groups.Conclusion The use of HFMEA management tools can effectively improve the intravenous thrombolysis process in patients with AIS.This can increase the rate of reperfusion therapy in AIS,shorten the time to DNT,and improve early neurological function.Additionally,it can promote patient health and reduce the burden on families.

Objective To assess the effectiveness of Healthcare Failure Mode and Effect Analysis(HFMEA)in the intravenous thrombolysis process for patients with Acute Ischemic Stroke(AIS).Methods The targeted and comprehensive emergency care plan was constructed using HFMEA methodology.This plan was then applied to optimize the intravenous thrombolysis process in the target hospitals.Key indicators were evaluated before and after the intervention using t-tests,chi-square tests,and non-parametric tests.Results After the implementation of HFMEA,the mean Risk Priority Number value for the intravenous thrombolysis process in AIS decreased compared to before implementation.Additionally,the rate of intravenous thrombolysis within 4.5 hours of onset increased to 54％.The HFMEA model management group showed an 8％improvement compared to the conventional management group.The median time between patient admission and the start of intravenous thrombolysis door to needle time(DNT)was shorter,hospitalisation costs were lower,and National Institutes of Health Stroke Scale scores were reduced at 1 and 2 weeks post-treatment,as well as at discharge.However,there was no significant difference in the number of hospital days between the two groups.Conclusion The use of HFMEA management tools can effectively improve the intravenous thrombolysis process in patients with AIS.This can increase the rate of reperfusion therapy in AIS,shorten the time to DNT,and improve early neurological function.Additionally,it can promote patient health and reduce the burden on families.

Objective To assess the effectiveness of Healthcare Failure Mode and Effect Analysis(HFMEA)in the intravenous thrombolysis process for patients with Acute Ischemic Stroke(AIS).Methods The targeted and comprehensive emergency care plan was constructed using HFMEA methodology.This plan was then applied to optimize the intravenous thrombolysis process in the target hospitals.Key indicators were evaluated before and after the intervention using t-tests,chi-square tests,and non-parametric tests.Results After the implementation of HFMEA,the mean Risk Priority Number value for the intravenous thrombolysis process in AIS decreased compared to before implementation.Additionally,the rate of intravenous thrombolysis within 4.5 hours of onset increased to 54％.The HFMEA model management group showed an 8％improvement compared to the conventional management group.The median time between patient admission and the start of intravenous thrombolysis door to needle time(DNT)was shorter,hospitalisation costs were lower,and National Institutes of Health Stroke Scale scores were reduced at 1 and 2 weeks post-treatment,as well as at discharge.However,there was no significant difference in the number of hospital days between the two groups.Conclusion The use of HFMEA management tools can effectively improve the intravenous thrombolysis process in patients with AIS.This can increase the rate of reperfusion therapy in AIS,shorten the time to DNT,and improve early neurological function.Additionally,it can promote patient health and reduce the burden on families.