BACKGROUND:Growth factor is the key effect molecule that plays a role in platelet-rich plasma in clinical treatment.There are differences in the concentration of growth factor after different activators activate platelet-rich plasma,which is an important factor affecting clinical efficacy. OBJECTIVE:To analyze the influence of different activators on the mass concentration of growth factors in platelet-rich plasma. METHODS:Totally 12 healthy volunteers were recruited to collect EDTA-K2 anticoagulant venous blood.Secondary centrifugation was used to prepare platelet-rich plasma.The difference in mass concentrations of growth factors was compared between venous blood and platelet-rich plasma.The platelet-rich plasma was mixed with four activators(normal saline,thrombin,calcium gluconate,calcium gluconate+thrombin)according to the volume ratio of 10:1,and incubated in a constant temperature water bath at 37 °C for 30 minutes.After centrifugation,the supernatant was extracted and the mass concentration of growth factor was detected.The bacterial growth in supernatant was measured by blood agar plate.Pearson correlation was used to analyze the correlation between different activators and the mass concentration of growth factor in platelet-rich plasma,and the correlation between the value of thrombocytometer and the mass concentration of growth factors in platelet-rich plasma. RESULTS AND CONCLUSION:(1)The mass concentrations of platelet-derived growth factor-BB,platelet-derived growth factor-AB,vascular endothelial growth factor,and epidermal growth factor in platelet-rich plasma were 8.7,22.2,2.3,and 2.8 times of those in venous blood,respectively(P<0.05).(2)Compared with normal saline group,the mass concentrations of platelet-derived growth factor BB,platelet-derived growth factor AB,vascular endothelial growth factor,and epidermal growth factor were increased in the thrombin group,calcium gluconate group,and calcium gluconate+thrombin group(P<0.05).The mass concentration of platelet-derived growth factor BB in the thrombin group and calcium gluconate group was higher than that in the calcium gluconate+thrombin group(P<0.05),and the mass concentration of platelet-derived growth factor AB in the thrombin group was higher than that in the calcium gluconate group and calcium gluconate+thrombin group(P<0.05).Epidermal growth factor mass concentration in the thrombin group was lower than that in the calcium gluconate group and calcium gluconate+thrombin group(P<0.05).(3)The results of blood agar plate test showed no bacterial growth in the supernatant of the four groups.(4)Pearson correlation analysis showed that the mass concentration of platelet-derived growth factor BB in platelet-rich plasma was strongly positively correlated with thrombin(r=0.683,P<0.05),and the mass concentration of vascular endothelial growth factor was strongly positively correlated with thrombin,calcium gluconate,calcium gluconate+thrombin stimulant(r=0.730,0.789,0.686,P<0.05).There was no correlation between the value of thrombocytometer and the mass concentration of four kinds of growth factors(P>0.05).(5)The results suggest that different activators have an impact on the concentration of growth factors in platelet-rich plasma.It is suggested to choose different activators to improve clinical efficacy according to different growth factor mass concentrations and treatment needs.

Objective To construct a targeted drug delivery system, Ang-BEVs@Dox, based on Angiopep-2 peptide-modified bacterial extracellular vesicles （BEVs） loaded with doxorubicin （Dox）, overcome the challenges of blood-brain barrier （BBB） penetration and systemic toxicity in chemotherapy for glioblastoma （GBM）, enhance drug targeting to brain tumors and reduce its toxic side effects. Methods BEVs derived from Escherichia coli were isolated using ultracentrifugation. The targeting ligand Angiopep-2, specific for the LRP-1 receptor, was conjugated onto the surface of BEVs to construct the targeted carrier （Ang-BEVs）. Dox was loaded into Ang-BEVs using low-frequency sonication to form Ang-BEVs@Dox. The physicochemical properties （morphology and size） of the carriers were characterized by transmission electron microscopy （TEM） and dynamic light scattering （DLS）. The BBB-penetrating capability, in vitro/in vivo anti-tumor efficacy, and biosafety of the system were evaluated using cellular uptake assays, 3D tumor spheroid models, and orthotopic tumor-bearing mouse models. Results ① Carrier characterization and in vitro efficacy: Ang-BEVs@Dox exhibited a particle size of approximately 100 nm and maintained structural stability after Dox loading. It significantly enhanced cellular uptake efficiency in U87MG cells and achieved deep penetration within 3D tumor spheroids. Cytotoxicity assays demonstrated synergistic anti-tumor effects between the BEVs and Dox in the Ang-BEVs@Dox system. ② In vivo targeting and anti-tumor efficacy: In orthotopic tumor-bearing mouse models, Ang-BEVs@Dox effectively penetrated the BBB and significantly inhibited tumor growth, extending the median survival time of tumor-bearing mice to 33.5 days （compared to 23.5 days in the blank control group, P<0.001）. Immunohistochemical analysis revealed significant suppression of the tumor cell proliferation marker Ki-67 and enhancement of the apoptosis marker TUNEL staining signals. ③ Biosafety: Major organs from mice in the Ang-BEVs@Dox treatment group showed no observable pathological damage, indicating good biosafety. Conclusion This study successfully constructed an Angiopep-2 peptide-modified engineered BEVs delivery system （Ang-BEVs@Dox）. Through Angiopep-2-mediated BBB penetration and tumor targeting, it significantly enhanced the accumulation and therapeutic efficacy of BEVs at the GBM site. This method combined efficient delivery, low systemic toxicity, and clinical translation potential, which provided an innovative solution to overcome the therapeutic bottleneck in GBM treatment.

In China, the number of chronic pain patients has exceeded 300 million, making chronic pain the third major health problem after tumors and cardiovascular diseases. Particularly concerning is the gradual emergence of hypertension and chronic low back pain as public health problems that threaten public health and increase the global economic burden. Modern research shows that the incidence of coexisting hypertension is higher among patients with chronic low back pain. Additionally, evidence indicates that the use of NSAIDs for pain relief can have adverse effects on blood pressure, and some antihypertensive medications may trigger symptoms of low back pain. Thus, addressing chronic pain in hypertensive patients while stabilizing blood pressure is one of the important research questions in the modern treatment of hypertension among middle-aged and elderly individuals. From ancient to modern traditional Chinese medicine(TCM) theory, kidney deficiency has been regarded as the core pathogenesis of low back pain. Recent clinical practices and literature indicate that kidney deficiency plays a crucial role in the modern pathogenesis of hypertension. Both hypertension and chronic low back pain are closely associated with kidney deficiency in TCM theory, revealing a potential mechanism linking the two conditions. Combining the theories of " kidney-essence-marrow" and " nourishing water to moisten wood", a therapeutic strategy centered on tobifying kidney was proposed, including selecting single drugs with kidney-tonifying effects as well as compound formulations and elaborating modern research evidence. The aim is to achieve stable blood pressure control in hypertension patients with chronic low back pain while providing a new treatment perspective for chronic low back pain. This article systematically elaborates on the understanding of hypertension combined with chronic low back pain from both TCM and modern medicine, as well as the therapeutic strategy involving kidney-tonifying drugs, to offer useful references for clinical practice.
Humans ; Hypertension/complications* ; Low Back Pain/complications* ; Drugs, Chinese Herbal/therapeutic use* ; Kidney/drug effects* ; Medicine, Chinese Traditional ; Chronic Pain/drug therapy*

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

OBJECTIVE: To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC₅₀, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins. RESULTS: Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group. CONCLUSION Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans ; Naphthoquinones/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/pathology* ; Cell Line, Tumor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Protein Kinases/metabolism* ; Signal Transduction ; Cell Survival/drug effects*

E3 ubiquitin ligase is a key enzyme that determines substrate specificity during ubiquitination and plays an important role in regulating the degradation of tumor suppressor or oncogenic proteins. E3 ubiquitin ligase is involved in regulating leukemia cell differentiation, cell cycle and immune response, and it is closely related to the occurrence and development of acute myeloid leukemia (AML). Targeting highly specific E3 ubiquitin ligase can be used as an effective treatment for AML. This article reviewed the latest progress of E3 ubiquitin ligase in the diagnosis and treatment of AML, aiming to provide insights for the precise targeted therapy of this disease.
Humans ; Ubiquitin-Protein Ligases/metabolism* ; Leukemia, Myeloid, Acute/therapy*

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Objective:To explore the influencing factors of olfactory impairment in patients with obstructive sleep apnea（OSA） and establish a nomogram prediction model. Methods:A total of 100 OSA patients were enrolled. Snap&Sniff olfactory test was used to evaluate the olfactory identification function and olfactory threshold of the patients. According to the scoring criteria, either olfactory identification scores below 14 points or olfactory threshold scores below 3 points was defined as olfactory impairment. Multivariate logistic regression analysis was used to explore the influencing factors of olfactory impairment in OSA. The nomogram model was constructed by using the R 4.4.2 software package. ROC curve, calibration curve and decision curve were used to evaluate the predictive efficacy, consistency and clinical utility of the model. Results:A total of 55 of 100 OSA patients had olfactory impairment. The results of multivariate logistic regression analysis showed that age, ESS score, MoCA score, and apnea-hypopnea index（AHI） were the influencing factors of olfactory impairment in OSA. Based on the above parameters, a nomogram model was established. The ROC curve analysis showed that the AUC was 0.897（95%CI 0.834-0.961）, indicating that the model had good predictive ability. The calibration curve showed that the predicted probability of the model fits the actual probability well. Decision curve analysis showed that when the threshold probability was in the range of 0-0.9, the model had a high clinical net benefit rate. Conclusion:Age, ESS score, MoCA score and AHI are the influencing factors of olfactory impairment in patients with OSA. The nomogram model constructed based on the above factors has good predictive value, which is conducive to the clinical multi-angle understanding of OSA and the formulation of scientific prevention and treatment measures.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Nomograms ; Olfaction Disorders/etiology* ; Logistic Models ; Middle Aged ; Male ; Female ; ROC Curve ; Adult ; Aged

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

Objective To analyze the influencing factors for intestinal colonization and secondary infection of car-bapenem-resistant Klebsiella pneumoniae(CRKP)in neonates,and provide a basis for formulating prevention and control strategies for CRKP infection.Methods Neonates who were admitted to the neonatal ward of a hospital from January 2021 to October 2022 were selected as the study subjects,and the first screening of CRKP was con-ducted within 48 hours after admission.In addition,active anal swab screening for carbapenem-resistant Ente-robacterales(CRE)was performed weekly during hospitalization,and the infection status of CRKP strains was mo-nitored.Clinical data of neonates in the colonization group,non-colonization group,and infection group were ana-lyzed.Intestinal colonized strains and the non-repetitive CRKP strains isolated from clinical specimens of neonates with secondary infection after colonization were performed carbapenemase gene detection,multilocus sequence ty-ping(MLST)and pulsed-field gel electrophoresis(PFGE)analysis.Results A total of 1 438 neonates were active-ly screened for CRE,174 were CRKP positive,CRKP colonization rate was 12.1％.Among 174 neonates,35 were with secondary infection,with the incidence of 20.1％.The independent risk factors for neonatal CRKP intestinal colonization were cesarean section(OR=2.050,95％CI:1.200-3.504,P=0.009),use of cephalosporins(OR=1.889,95％CI:1.086-3.288,P=0.024),nasogastric tube feeding(OR=2.317,95％CI:1.155-4.647,P=0.018).Protective factors were breast-feeding(OR=0.506,95％CI:0.284-0.901,P=0.021),oral probiotics(OR=0.307,95％CI:0.147-0.643,P=0.002),and enema(OR=0.334,95％CI:0.171-0.656,P=0.001).Independent risk factors for secondary infection after intestinal colonization of neonatal CRKP were carbapenem anti-biotic use(OR=19.869,95％CI:1.778-222.029,P=0.015)and prolonged hospital stay(OR=1.118,95％CI:1.082-1.157,P＜0.001).The detection results of drug resistance genes showed that carbapenemase-producing genes of CRKP strains were all blaKPC-2,all belonged to type ST11.Homologous analysis showed that intestinal CRKP colonization was highly homologous with the secondary infection strains after colonization.Conclusion CRKP intestinal colonization during neonatal hospitalization may increase the risk of CRKP infection.Risk and pro-tective factors of neonatal intestinal colonization and secondary infections after colonization should be paid attention,and corresponding preventive and control measures should be taken,so as to reduce the occurrence and transmission CRKP healthcare-associated infection.