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.

Objective:To analyze the radiographic parameters of shoulder balance that affect the postoperative satisfaction of Lenke type 1 adolescent idiopathic scoliosis (AIS).Methods:A total of 98 patients with AIS who underwent posterior pedicle screw fusion in Xijing Hospital of Air Force Medical University from August 2017 to July 2020 were retrospectively analyzed. There were 26 males and 72 females, aged 15.2±5.3 years (range, 10-24 years). Distribution of upper instrumented vertebrae: T 2 58 cases (59%), T 3 25 cases (26%), T 4 15 cases (15%); Distribution of lower instrumented vertebrae: T 12 63 cases (64%), L 1 28 cases (29%), L 2 4 cases (4%), L 3 3 cases (3%). Clavicle angle (CA), radiographic shoulder height (RSH), and coracoid height difference (CHD), clavicle-rib cage intersection difference (CRID), T 1 tilt angle, first rib tilt angle, clavicle chest angle difference(CCAD) and Scoliosis Research Society-22 (SRS-22) scale were compared before and after operation. Binary logistic regression was used to analyze the radiographic indicators of shoulder balance that affected the postoperative satisfaction of Lenke type 1 AIS. The receiver operating characteristic (ROC) curve was drawn to determine the threshold value of the imaging index. Results:All operations were successfully completed. The operation time was 260±80 min (range, 220-320 min), and the intraoperative blood loss was 360±110 ml (range, 300-700 ml). There was no nerve, dural or vascular injury during operation. RSH, CHD, CRID, T 1 tilt angle, first rib tilt angle, and CCAD at the final follow-up were 4.0 (0, 13.9) mm, 7.0 (0, 12.9) mm, 4.0 (0, 10.0) mm, 4.8° (3.3°, 8.2°), 5.3°±3.9°, and 5.5° (3.0°, 8.9°), respectively, which were less than the preoperative 10.6 (2.0, 20.3) mm, 10.3 (2.5, 15.9) mm, 8.0 (1.0, 15.2) mm, 7.6° (3.5°, 12.2°), 7.5°±6.9°, 8.5° (3.6°, 18.3°), and the difference was statistically significant ( P<0.05). The SRS-22 function, pain, appearance, and psychological scores at the final follow-up were 4.6 (4.0, 4.9), 4.1±0.5, 4.1±0.7, and 4.2 (3.9, 4.8) points, respectively, which were greater than the preoperative scores of 4.2 (3.8, 4.6), 4.0±0.7, 3.5±0.7, and 4.0 (3.5, 4.4) points, the difference was statistically significant ( P<0.05). Binary logistic regression showed that CCAD was an independent radiographic indicator of shoulder balance that affected the satisfaction of AIS patients after orthopaedic surgery ( OR=0.826, P=0.040). ROC curve showed that the area under the curve and 95% CI was 0.726 (0.572, 0.865), and the threshold was 6.6°. Conclusion:CCAD is an independent radiographic parameter of shoulder balance that affects the postoperative satisfaction of AIS. Patients are more likely to achieve a satisfactory outcome when their postoperative CCAD is ≤6.6°, which can be used clinically as a radiographic parameter to assess the efficacy of orthopaedic spine surgery.

Osteosarcoma （OS） is the most common primary malignant bone tumor originating from mesenchymal stem cells， which features high degree of malignancy， strong invasiveness， easy early metastasis， and high recurrence rate. The clinical manifestations of OS are pain， local mass， limited movement， and pathological fracture. OS mainly occurs in children， adolescents， and the elderly， seriously threatening physical and mental health of patients， as well as their quality of life. The currently available therapies for OS are surgery， chemoradiotherapy， and the combination of the two. Although the therapeutic effect has been improved， tumor recurrence and metastasis and multidrug resistance still occur. Thus， the therapeutic effect is not satisfactory， especially in improving the overall survival rate of patients with metastatic OS. As a result， clinicians and researchers have been making efforts to find an effective therapy. In recent years， the mechanism of curcumin （CUR） against OS has attracted wide attention. CUR， a pigment extracted from the rhizomes or tubers of many plants， such as Curcuma longa， C. rcenyujin， and C. phaeocaulis， has a variety of pharmacological effects. Scholars have found that CUR has the effects of inhibiting proliferation， inducing apoptosis， and reversing multidrug resistance （MDR） of tumor cells， but also it has poor water solubility and low bioavailability， which limit the clinical application. This paper mainly discusses the mechanism of CUR against OS， the existing problems， new treatment methods， and future research directions， which is expected to provide new ideas for scientific researchers and provide a reference for the development and utilization of CUR in the future.

OBJECTIVE: To develop monoclonal antibodies that can specifically recognize human von Willebrand factor (VWF) propeptide (VWFpp) in plasma, and establish a rapid and reliable method for the detection of VWFpp antigen in plasma by using the double-antibody sandwich ELISA with the obtained anti-VWFpp monoclonal antibody. METHODS: The recombinant human VWFpp (D1 and D2 regions) protein expressed in eukaryotic cells was used as immunogen to immunize BALB/c mice with routine method, so as to obtain clones of fusion cells. After screening and identification, hybridoma cell lines secreting monoclonal antibodies against VWFpp were selected, and then double-antibody sandwich ELISA assay was used to construct VWFpp antigen detection kit for the determination of VWFpp in human plasma. The levels of VWFpp antigen in plasma of 12 leukemia patients who underwent bone marrow transplantation were dynamically detected. RESULTS: Two hybridoma cell lines that can be subcultured continuously and secrete monoclonal antibodies against VWFpp were obtained and named SZ175 and SZ176 respectively. Identified by ELISA and Western blot, the antibodies could both specifically recognize VWFpp but couldn't recognize mature VWF (without propeptide). Based on the principle of double-antibody sandwich ELISA, monoclonal antibodies SZ175 and SZ176 were successfully made into a kit for detecting VWFpp antigen. The plasma VWFpp levels of leukemia patients before and after bone marrow transplantation were dynamically detected. The results showed that the plasma VWFpp levels of the patients after transplantation were significantly higher than those before transplantation. CONCLUSION Two monoclonal antibodies against VWFpp were successfully prepared, and a double-antibody sandwich ELISA detection kit for VWFpp antigen was constructed, which provides a powerful tool for further study on the biological function of VWFpp, the clinical diagnosis and classification of von Willebrand disease (VWD), and the prognostic monitoring of endothelial injury-related diseases.
Animals ; Mice ; Humans ; von Willebrand Factor ; Antibodies, Monoclonal ; Protein Precursors/metabolism* ; von Willebrand Diseases/diagnosis* ; Prognosis

Urethral plate (UP)-preserving urethroplasty is simple and has few complications, but it may affect the development of penis in the long term and lead to recurrent chordee. In this study, we used obliquely cut UP to repair hypospadias with mild chordee after degloving (15°-30°) and compared the results with onlay urethroplasty to explore its rationality and feasibility. Between April 2018 and October 2020, 108 hypospadias patients underwent onlay urethroplasty or modified onlay urethroplasty. Clinical data were prospectively collected, and medium-term outcomes were assessed at follow-up. The complications were compared between the two groups. Forty-four patients underwent the modified onlay procedure (Group I), with follow-up time (mean ± standard deviation [s.d.]) of 23.2 ± 4.5 (range: 17-31) months. Sixty-four patients underwent a standard onlay procedure (Group II), with follow-up time (mean ± s.d.) of 39.7 ± 3.9 (range: 32-46) months. There was no difference in age at surgery. The urethral defect length and operative time were longer in Group I. Six cases of fistula and one case each of stricture and diverticulum were reported in Group I. In Group II, 11 cases of fistula and one case each of stricture and diverticulum were reported. The complication rates were 18.2% and 20.3% in Group I and Group II, respectively (P > 0.05). These medium-term follow-up results demonstrate that the modified onlay procedure (oblique cut UP urethroplasty) is a safe and feasible technique for hypospadias with mild chordee after degloving. Compared with standard onlay urethroplasty, this modified procedure is conducive to the complete removal of scar tissue underlying the UP without increasing the risk of surgical complications.
Male ; Humans ; Infant ; Hypospadias/surgery* ; Cicatrix/surgery* ; Constriction, Pathologic/surgery* ; Urethra/surgery* ; Diverticulum ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome

OBJECTIVE: To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity. METHODS: Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively. RESULTS: DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05). CONCLUSION DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.
Apoptosis ; Caspase 3 ; Caspase 9/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Doxycycline/pharmacology* ; Humans ; Mitogen-Activated Protein Kinase Kinases/pharmacology* ; Multiple Myeloma

Purpose: This study aimed to investigate the potential systemic antitumor effects of stereotactic ablativeradiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods: Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor;irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grewto the touchable size, mice were randomly divided into eight treatment groups. These groupsreceived normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not tothe primary tumor. The further tumor growth/regression of mice were followed andobserved. Results: For the single 15 Gy modality, tumor growth delay could only be observed at the primarytumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primaryand secondary tumor growth could be observed, indicated an abscopal effect wasinduced. Mechanism analysis suggested that programmed death-ligand 1 expressionincreased with SABR was counteract by additional apatinib therapy. Furthermore, whenapatinib was combined with SABR, the composition of immune cells could be changed.More importantly, this two-pronged approach evoked tumor antigen–specific immune responsesand the mice were resistant to another tumor rechallenge, finally, long-term survivalwas improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib,which was effective in eliciting an abscopal effect induced by SABR.

Iridoid synthase( IS),the key enzyme in the natural biosynthesis of vegetal iridoids,catalyzes the irreversible cyclization of 10-oxogeranial to epi-iridodial. In this study,we screened the Rehmannia glutinosa transcriptome data by BLASTn with Catharanthus roseus CrIS cDNA,and found four c DNA fragments with length of 1 527,1 743,1 425,1 718 bp,named RgIS1,RgIS2,RgIS3 and RgIS4,respectively. Bioinformatics analysis revealed that the four iridoid synthase genes encoding proteins with 389-392 amino acid residues,protein molecular weights were between 44. 30-44. 74 k Da,and theoretical isoelectric points were between 5. 30 and 5. 87. Subcellular localization predictions showed that the four iridoid synthase were distributed in the cytoplasm. Structure analysis revealed that R. glutinosa iridoid synthases contain six conserved short-chain dehydrogenase/reductase( SDR) motifs,and their 3 D models were composed typical dinucleotide-binding " Rossmann" folds covered by helical C-terminal extensions. Using the amino acid sequences of four R. glutinosa iridoid synthases,phylogenetic analysis was performed,the result indicated that RgIS3,CrIS and Olea europaea OeIS were grouped together,the other R. glutinosa iridoid synthases and fifteen proteins in other plants had close relationship. Real-time fluorescent quantitative PCR revealed that RgIS1 and RgIS3 highly expressed in unfold leaves,however,RgIS2 and RgIS4 highly expressed in stems and tuberous roots,respectively. RgIS3 showed higher expression levels in non-radial striations( nRS) of the two cultivars,and RgIS1 and RgIS2 had higher expression levels in nRS of QH,while RgIS4 had less expression levels in nRS of QH1. RgIS1,RgIS2 and RgIS3 were up-regulated by Me JA treatment,although the time and degree of response differed. Our findings are helpful to reveal molecular function of R. glutinosa iridoid synthases and provide a clue for studing the molecular mechanism of iridoid biosynthesis.
Cloning, Molecular ; Genes, Plant ; Iridoids ; metabolism ; Ligases ; genetics ; Phylogeny ; Rehmannia ; enzymology ; genetics

Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 μmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells.
Antibiotics, Antineoplastic ; pharmacology ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21 ; biosynthesis ; Doxorubicin ; analogs & derivatives ; pharmacology ; Drug Screening Assays, Antitumor ; methods ; Female ; G1 Phase ; drug effects ; G2 Phase ; drug effects ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Oligopeptides ; pharmacology ; Signal Transduction ; drug effects ; Tumor Suppressor Protein p53 ; biosynthesis

AIM: JS-38 (mitothiolore), a synthetic version of a metabolite isolated from Xenorhabdus sp., was evaluated for its anti-tumor and white blood cell (WBC) elevating activities. METHOD: These anti-proliferative activities were assessed in vitro using a panel of ten cell lines. The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice. The anti-tumor interactions of JS-38 and cyclophosphamide (CTX) or 5-fluorouracil (5-Fu) were studied in a S180 sarcoma model in ICR mice. Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX- and 5-Fu-induced neutropenic mice. RESULTS: The IC50 values ranged from 0.1 to 2.0 μmol·L(-1). JS-38 (1 μmol·L(-1)) caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38 (15, 30, and 60 mg·kg(-1)·d(-1)) inhibited in vivo tumor progression without a significant effect on body weight. JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu. JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor (G-CSF). In mice with neutropenia induced by CTX or 5-Fu, JS-38 rapidly restored neutrophil counts. CONCLUSION These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils.
Animals ; Antineoplastic Agents ; administration & dosage ; metabolism ; Cell Count ; Female ; Humans ; Hydrocarbons, Fluorinated ; administration & dosage ; metabolism ; Lung Neoplasms ; drug therapy ; physiopathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Neutrophils ; cytology ; drug effects ; Xenorhabdus ; chemistry ; metabolism