Objective:To evaluate the acute toxicities and related influencing factors of vertebral-body-sparing proton craniospinal irradiation (VBSpCSI) using pencil beam scanning (PBS) technology in pediatric patients, and to assess spinal growth and survival outcomes.Methods:A retrospective analysis was conducted on 70 pediatric patients treated with PBS-based VBSpCSI at Hebei Yizhou Cancer Hospital between January 2020 and December 2022, and continued to follow up until November 2023. Acute toxicities were assessed, and linear regression analysis combined with receiver operating characteristic curve were employed to investigate the dose-effect relationship between vertebral dose and toxicities. Spinal growth after radiotherapy was evaluated by measuring the Cobb angle on follow-up MRI. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.Results:The median age of patients at the time of irradiation was 6 years (range, 2-16 years). Two patients (3%) developed grade ≥3 gastrointestinal toxicities, while 7 patients (10%) experienced grade 1 radiation-induced esophagitis. The nadirs of white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) during treatment were significantly negatively correlated with vertebral V 5 Gy ( P=0.009, 0.006, 0.001) and vertebral V 20 Gy ( P=0.007, 0.011, <0.001). When vertebral V 5 Gy<86.5% and vertebral V 20 Gy<73.2%, the incidence of grade ≥3 myelosuppression was significantly reduced ( P<0.001, =0.001). Additionally, younger patient age (in months) and concurrent chemotherapy were also significantly associated with increased acute hematologic toxicity. Among 43 patients with MRI follow-up, no scoliosis, kyphosis, or chronic lumbosacral pain was observed. The 3-year OS and PFS rates were 95.7% and 86.4%, respectively. Conclusions:PBS-based VBSpCSI in pediatric patients demonstrates manageable acute toxicities, with a clear dose-effect relationship between vertebral V 5 Gy , V 20 Gy and hematologic toxicities, and the incidence of non-hematological toxicities remains low. No adverse effects on spinal growth or survival outcomes were observed in the short term.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

Objective:To evaluate the acute toxicities and related influencing factors of vertebral-body-sparing proton craniospinal irradiation (VBSpCSI) using pencil beam scanning (PBS) technology in pediatric patients, and to assess spinal growth and survival outcomes.Methods:A retrospective analysis was conducted on 70 pediatric patients treated with PBS-based VBSpCSI at Hebei Yizhou Cancer Hospital between January 2020 and December 2022, and continued to follow up until November 2023. Acute toxicities were assessed, and linear regression analysis combined with receiver operating characteristic curve were employed to investigate the dose-effect relationship between vertebral dose and toxicities. Spinal growth after radiotherapy was evaluated by measuring the Cobb angle on follow-up MRI. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.Results:The median age of patients at the time of irradiation was 6 years (range, 2-16 years). Two patients (3%) developed grade ≥3 gastrointestinal toxicities, while 7 patients (10%) experienced grade 1 radiation-induced esophagitis. The nadirs of white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) during treatment were significantly negatively correlated with vertebral V 5 Gy ( P=0.009, 0.006, 0.001) and vertebral V 20 Gy ( P=0.007, 0.011, <0.001). When vertebral V 5 Gy<86.5% and vertebral V 20 Gy<73.2%, the incidence of grade ≥3 myelosuppression was significantly reduced ( P<0.001, =0.001). Additionally, younger patient age (in months) and concurrent chemotherapy were also significantly associated with increased acute hematologic toxicity. Among 43 patients with MRI follow-up, no scoliosis, kyphosis, or chronic lumbosacral pain was observed. The 3-year OS and PFS rates were 95.7% and 86.4%, respectively. Conclusions:PBS-based VBSpCSI in pediatric patients demonstrates manageable acute toxicities, with a clear dose-effect relationship between vertebral V 5 Gy , V 20 Gy and hematologic toxicities, and the incidence of non-hematological toxicities remains low. No adverse effects on spinal growth or survival outcomes were observed in the short term.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective To investigate the relationship of the expression levels of serum miR-140 and miR-211 in elderly patients with coronary heart disease(CHD)and collateral circulation forma-tion.Methods A total of 151 CHD elderly patients undergoing surgical treatment in our hospital were included as the study subjects,and were divided into non-collateral circulation group(100 cases)and collateral circulation group(51 cases)according to the presence or absence of collateral circulation.RT-qPCR was applied to detect the expression levels of miR-140 and miR-211 in the serum.Results Larger proportions of culprit coronary artery＞3 branches and stenosis ≥75％and higher serum miR-211 level,but lower miR-140 level were observed in the non-collateral cir-culation group than the collateral circulation group(P＜0.01).The number of coronary artery lesions and the severity of coronary artery stenosis were negatively correlated with serum miR-140 level(r=-0.546,P＜0.01;r=-0.562,P＜0.01),and positively with miR-211 level(r=0.539,P＜0.01;r=0.528,P＜0.01).Multivariate logistic regression analysis indicated that miR-140 was a protective factor while miR-211 was an independent risk factor for collateral circulation formation in elderly CHD patients(P＜0.01).The area under the curve of the two indicators com-bined together in predicting collateral circulation formation was 0.896(95％CI:0.834-0.938,P＜0.05).Conclusion Serum miR-140 and miR-211 are both influencing factors for collateral cir-culation formation,and their combination has high predictive value for the formation.

Objective: To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies. Methods: Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP, Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese bio-medical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are: (1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4) data from multiple reports but originated from one study, where we extract information from all reports; (5) guidelines, includes: national or academic guidelines/experts 'consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses). Results: Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and finally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing. Conclusions ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.

Objective:To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies.Methods:Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP, Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese biomedical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are: (1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4) data from multiple reports but originated from one study, where we extract information from all reports; (5) guidelines, includes: national or academic guidelines/experts 'consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses).Results:Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and finally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing.Conclusions:ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.

Objective To investigate the influences of culture conditions on the in vitro induction and maturation of dendritic cells by using different combinations of cytokines. -ethods Mouse bone mar-row cells were isolated and cultured in media containing varying combinations of cytokines, including granu-locyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and fms-like tyrosine kinase 3 ligand (Flt3L). After cultured at 37℃ for seven days, the attached bone marrow cells were collected and stained by fluorescence-labeled monoclonal antibodies (McAb) against CD11c, MHCⅡ and CD86 for flow cytometry analysis. In the parallel group, LPS was added on day 5 to a final concentration of 1μg/ml for DC maturation analysis by flow cytometry. Results In group Flt3L (20 ng/ml)/GM-CSF (20 ng/ml)/IL-4 (10 ng/ml), 90％ of bone marrow cells were CD11c-positive. Flt3L (100 ng/ml) could induce 88％ of bone marrow cells to express CD11c. Bone marrow cells positive for MHCⅡ accounted for 35. 4％ and 36. 1％ in group Flt3L/GM-CSF/IL-4 and group Flt3L/GM-CSF, where both Flt3L and GM-CSF were used at a concentration of 20 ng/ml. After LPS stimulation, the positive rates of MHCⅡ in group Flt3L/GM-CSF/IL-4 and group Flt3L/GM-CSF were 58. 1％ and 59. 6％, which increased by 22. 7％ and 23. 5％, re-spectively. The percentages of CD86-positive bone marrow cells were 7. 1％ and 5. 5％ in group Flt3L/GM-CSF/IL-4 and group Flt3L/GM-CSF. Bone marrow cells positive for CD86 grew by 7. 1％ and 6. 2％ in group Flt3L (20 ng/ml) and group GM-CSF/IL-4 after LPS stimulation. Conclusions Flt3L and GM-CSF probably dominated the differentiation and maturation of bone marrow-derived dendritic cells with a synergis-tic effect. Combined usage of Flt3L and GM-CSF at the concentration of 20 ng/ml would be an optimal proto-col for DC research.