Objective To investigate the effect of cinobufacini on immune escape of acute myeloid leukemia(AML)by regulating myosin heavy chain 9(MYH9)/ubiquitin-specific protease 7(USP7)/cellular-myelocytomatosis viral oncogene(c-MYC)pathway.Methods(1)In vivo experiment:a nude mouse xenograft tumor model was established to evaluate the effect of cinobufotalin on the growth and immune escape of AML cells in vivo.(2)In vitro experiments:human AML cell line HL-60 was treated with different concentrations of cinobufacini,cell viability was detected by cell counting kit 8(CCK-8),and HL-60 cell invasion was detected by Transwell assay.HL-60 cells were co-cultured with activated CD8+ T cells,the expression of CD25,the surface marker of CD8+ T cells,was detected by flow cytometry,the levels of cytokines[interleukin-2(IL-2)and interferon(IFN-γ)]in the co-culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).CytoTox96 non-radioactive cytotoxicity assay was used to evaluate the cytotoxicity of CD8+ T cells to HL-60 cells.The protein expressions of MYH9,USP7 and c-MYC in HL-60 cells were detected by Western Blot.The interaction between MYH9,USP7 and ubiquitination was detected by co-immunoprecipitation(Co-IP)assay.The MYH9 overexpression plasmid was tranfected to verify the mechanism of cinobufacini in AML.Results Cinobufacini treatment inhibited xerograft tumor growth in nude mice and enhanced the anti-tumor ability of CD8+ T cells.Cinobufacini treatment inhibited HL-60 cell viability and invasion in a concentration-dependent manner.Cinobufacini treatment up-regulated the expression of CD25,a surface marker of CD8+ T cells,and also up-regulated the levels of IL-2 and IFN-γ.Cinobufotalin enhanced the toxicity of CD8+ T cells to HL-60 cells.Cinobufacini inhibits the protein expressions of MYH9,USP7 and c-MYC in HL-60 cells.MYH9 promotes c-MYC deubiquitination by recruiting USP7,but cinobufacini inhibits MYH9-mediated c-MYC deubiquitination.Conclusion Cinobufacini can reduce the recruitment of c-MYC by deubiquitinating enzyme USP7 by inhibiting the expression of MYH9,and promote the ubiquitination and degradation of c-MYC,thereby inhibiting the immune escape of AML cells.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

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.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To explore national standard of occupational skills for assistive technology consultants in China based on the study of relevant international standards. Methods:After analyzing the international and some other national job content, work requirements, professional education and vocational training, and vocational standards of assistive technology consultants, the national occupational skills standard for assistive technology consultants in China was established referring to the compiling rules of national occupational skills standard. Results:According to the compiling rules of national occupational skills standard, the national occupational skills standard for assistive technology consultants in China included career situation, basic requirements, job requirements, and weight table, etc. Conclusion:The vocational development, structural framework and content of professional capacity for assistive technology consultants are studied. The draft of national occupational skills standard for rehabilitation assistive technology consultants has been compiled.

Objective Transplantation of bone marrow mesenchymal stem cells (BMSCs) has a good prospect of application for cerebral infarction,but the environment and the inflammatory response to ischemia and hypoxia after cerebral infarction are not con-ducive to the survival of transplanted cells. This article investigated the effects of Shuxue Tongmai capsule(SXTM) combined with BM-SCs transplantation on the improvement of cerebral ischemic injury in rats. Methods A model of middle cerebral artery occlusion was es-tablished in Sprague-Dawley(SD) rats using thread method and these 15 SD rats were randomly divided into model group,BMSCs group and combination therapy group (BMSCs transplantation combined with SXTM treatment). At 24h after modeling,rats in combination therapy group were given tail vein injection of 1 mL BMSCs suspension (2× 109 per/L) and gavage administration of SXTM 0. 64 g/kg. Rats in BMSCs group were given tail vein injection of 1 mL BMSCs suspension (2×109 per/L) and gavage administration of equal volume of sa-line. For model group,the rats were given tail vein injection of equal volume of PBS and gavage administration of equal volume of sa-line. Neurologic function was assessed before cell transplantation and at 3,7,14,28 days after cell transplantation to check the injury of neurologic function. At 28 days after transplantion,the rats were decapitated after anesthesia to take brain tissues for immunohisto-chemical detection of vascular endothelial growth factor(VEGF) and brain-derived neurotrophic factor(BDNF) protein expression. Mor-phological changes of the brain tissue and apoptosis in cortical neurons were observed and detected by hematoxylin-eosin staining and TUNEL,respectively. Results At 7,14,28 days after transplantation,the neurological defect score in combination therapy group was significantly lower than those of model group and BMSCs group(P<0.05). In each group,the neurological defect score at 3 days after transplantation was significantly decreased compared with those before transplantation(P<0.05). In the same group,the neurologi-cal defect scores at 14,28 days after transplantation were significantly decreased compared with those at 7 days after transplantation (P<0.05). The neurological defect scores at 14,28 days after transplantation were significantly decreased compared with those at 7 days after transplantation(P<0.05). The neurological defect score at 28 day after transplantation was significantly decreased compared with that at 7 day after transplantation(P<0.05). At 28 day after transplantation,the number of apoptotic cells in combination therapy group (51.40±4.04) was significantly fewer than those of model group (74.80±5.31) and BMSCs group (67.20±4.66) and the num-ber of apoptotic cells in BMSCs group was significantly decreased compared with model group(P<0.05). The results of immunohisto-chemistry showed that the VEGF and BDNF positive cells in the cerebral ischemic region of rats were brownish or sepia in color. Com-pared with model group,the expression levels of VEGF and BDNF protein in BMSCs group and combination therapy group were signifi-cantly increased (P<0.05),and that of combination therapy group was significantly increased compared with BMSCs(P<0.05). Conclusion SXTM combined with BMSCs transplantation can promote neurological recovery from cerebral ischemia by increasing the protein expression of VEGF and BDNF and reducing neuronal apoptosis.

OBJECTIVE: To investigate the effects of the Arg-Gly-Asp polypeptedes (RGD) peptides-modified porous tantalum surface on osteoblasts morphology and expressions of osteogenesis factors, and to evaluate RGD peptides promotes junctura ossium of tantalum-bone interface in vivo. METHODS: RGD peptides of different concentrations (1 g/L, 5 g/L, and 10 g/L) were loaded to porous tantalum slices with a diameter of 10 mm and a thickness of 3 mm by physical absorption. The 3rd generation of MG63 cells were co-cultured with tantalum and divided into 4 groups: Ta-cells (control) group, 1 g/L cells/Ta/RGD group, 5 g/L cells/Ta/RGD group, and 10 g/L cells/Ta/RGD group. Porous tantalum compo-sites and osteoblasts-tantalum interface were observed by scanning electron microscopy. The adhesion rate of osteoblasts was detected and immunocytochemistry was used to detect the expressions of filamentous actin (F-actin), osteocalcin (OC) and fibronectin (FN). RESULTS: The scanning electron microscope (SEM) revealed that osteoblasts distributed on the surface of porous tantalum and secreted extracellular matrix on outside and inner of micro-pores. The osteoblasts adhesion rate on porous tantalum modified with RGD was higher than that in the unmodified porous tantalum at the end of 24, 48, and 72 hours. The best adhesion effect was got in 5 g/L cells/Ta/RGD group at hour 48 [(68.07±3.80) vs. (23.40±4.39), P<0.05]. The results of immunocytochemistry showed that the expressions intensity of F-actin, OC and FN in osteoblasts on porous tantalum modified groups with RGD were stronger than that in the unmodified groups, and the expressions of 5 g/L cells/Ta/RGD group were significantly higher than those in the 10 g/L group and 1 g/L group [OC: (18.08±0.08) vs. (15.14±0.19), P<0.05; (18.08±0.08) vs. (14.04±0.61), P<0.05. FN: (24.60±0.98) vs. (15.90±0.53), P<0.05; (24.60±0.98) vs. (15.30±0.42), P<0.05. F-actin: (29.20±1.31) vs. (24.50±1.51), P<0.05; (29.20±1.31) vs. (16.92±0.40), P<0.05]. Correspondingly F-actin in osteoblasts was showed in longitudinal arrangement, and the expressions intensity was stronger than those OC and FN. CONCLUSION The RGD peptides is beneficial to enhance adhesion of osteoblast, spreading and reorganization of cytoskeleton on porous tantalum surface and improve the interface morphology, further promoting osteoblasts-tantalum conjunctive interface osseointegration.
Cell Adhesion ; Oligopeptides ; Osteoblasts/physiology* ; Osteogenesis ; Tantalum

Objective To explore the effect of improving clinical practice ability of nursing undergraduates via double evaluation.Methods From September 2015 to May 2016, 61 nursing undergraduates enrolled in 2012 to Guangzhou University of Chinese Medicine were selected by convenience sampling method and divided randomly according to their student number into experimental group (30 cases) and control group (31 cases). According to the double evaluation method adopted in the experimental group, clinical teaching scheme was modified dynamically. In the control group, clinical teaching was conducted according to clinical teaching scheme made by the university, with OSCE and evaluation form of clinical practice ability as tools for observer and self evaluation.Results Within the experimental group, both scores of observer evaluation in OSCE and scores of self evaluation in clinical practice behavior showed a trend of going up in phases (P<0.05). In comparison of observer evaluation in OSCE at the 9th month, scores of the experimental group were all higher than those in the control group in all dimensions except writing of nursing documents (P<0.05). In comparison of self evaluation in clinical practice behavior at the 9th month, scores of the experimental group were all higher than those in the control group in all dimensions except communication ability, slightly lower (P<0.05).Conclusions With the double evaluation method adopted, dynamically modified clinical teaching scheme according to phases can obviously improve clinical practice ability of nursing students.

OBJECTIVETo explore the expression of CC-chemokine Receptor 7 (CCR7) in adult acute leukemia patients, and to analyze the relationship of CCR7 expression with the clinical characteristics of patients.

METHODSThe expression of CCR7 in bone marrow samples from adult acute leukemia patients were detected by flow cytometry (FCM), the relationship of CCR7 expression with the clinical characteristics of patients such as sex, age, WBC count, blast cell ratio, CD56 expression, molecular biology, cell genetics, risk stratification, extramedullary infiltration was analyzed.

RESULTSThe expression rate of CCR7 in adult ALL and AML patients was 36.8% and 9.6%, respectively, and the expression level of CCR7 in ALL patients was higher than that in AML patients (P < 0.05). The extramedullary infiltration rate was 100% and 41.7 % for CCR7 positive and negative groups of ALL, respectively (P < 0.05). While the mean fluorescence intensity (MFI) in extramedullary infiltration group of ALL was higher than that in none-extramedullary infiltration group of ALL (50.00 ± 10.42 vs 18.14 ± 1.39), respectively (P < 0.05).

CONCLUSIONCCR7 is higher expressed in adult acute leukemia cells, moreover its expression rate in ALL is higher than that in AML, and the expression of CCR7 is related with extramedullary infiltration in ALL.

Adult ; Bone Marrow ; metabolism ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Leukocyte Count ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; Receptors, CCR7 ; genetics ; metabolism

OBJECTIVETo explore the effectiveness of absorbable hemostatic fluid gelatin in preventing postoperative cerebrospinal fluid leakage.

METHODSThe clinical data of 17 patients with dura mater tear were retrospectively analyzed from March to September in 2003. There were 16 males and 1 female, aged from 16 to 67 years old with an average of (39.6 ± 15.4) years. The injury site was at cervical vertebrae in 1 case, thoracic vertebrae in 9 cases, thoracolumbar junction in 4 cases, lumbar vertebrae in 3 cases. There were burst fracture in 4 cases and fracture-dislocation in 13 cases. According to ASIA grade, 12 cases were grade A, 2 cases were grade B, 2 cases were grade D, 1 case were grade E. Two cases caused by traffic accident, 10 by high falling, 4 by heavy parts crash, 1 by stairs fell during the earthquake. Absorbable hemostatic fluid gelatins were used to plug the dura mater tear,in order to prevent postoperative cerebrospinal fluid leakage. Postoperative drainage were recorded every day.

RESULTSOf 17 patients, 15 cases did not develop with cerebrospinal fluid leakage. Two cases develop with cerebrospinal fluid leakage after operation and their drainage were removed at 6 to 7 days after operation. In all cases, no complications related with cerebrospinal fluid leakage occurred, such as headache, dizzy, fever,neck resistance, rash, incision disunion, incision infection, hematoma, neurologic symptoms aggravation. No abnormal phenomena was found on incision surrounding at follow-up of 9 months.

CONCLUSIONUsing absorbable hemostatic fluid gelatin to plug the dura mater tear during operation is an effective method in preventing postoperative cerebrospinal fluid leakage.

Adolescent ; Adult ; Aged ; Cerebrospinal Fluid Leak ; prevention & control ; Female ; Gelatin ; administration & dosage ; Hemostatics ; administration & dosage ; Humans ; Male ; Middle Aged ; Postoperative Complications ; prevention & control