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.

ObjectiveThis study aims to explore risk factors for the development of major adverse cardiovascular and cerebrovascular events （MACCEs） in middle-aged and elderly patients with type 2 diabetes mellitus complicated with stable angina pectoris （T2DM-SAP） based on real-world clinical data in traditional Chinese medicine （TCM）， so as to develop a COX proportional risk prediction model and visualize the predicted results using a nomogram. MethodBased on the clinical scientific research information sharing system， the medical records of 586 T2DM-SAP patients （45-94 years old） were collected from January 2012 to December 2019， including age， gender， course of disease， major medical history， laboratory examination， tongue image， pulse image， TCM syndrome， and major treatment drugs. MACCE outcome indicators of patients were obtained by telephone follow-up and re-hospitalization records. The data was divided into a training set and a validation set according to 7∶3. In the training set， COX univariate analysis was used to determine the risk factors for MACCE in T2DM-SAP patients， and then variables were screened by forward-backward stepwise regression method， so as to establish a MACCE risk prediction model and construct a nomogram. The predictive efficacy of the model was reflected by the C-index， receiver operating characteristic （ROC） curve， calibration map， and clinical decision curve. ResultThe history of cerebrovascular disease ［Hazard ratio （HR）=1.983， 95% confidence interval （CI，1.314-2.993）］， low-density lipoprotein （LDL-C/mmol·L^-1）≥4.1［HR=2.683， 95%CI（1.461-4.925）］， dull red tongue ［HR=1.955， 95%CI（1.273-3.002）］， dull purple tongue ［HR=4.214， 95%CI（2.017-8.803）］， white thick coating ［HR=3.030， 95%CI（1.634-9.293）］， thin and weak pulse ［HR=2.233， 95%CI（1.283-3.888）］， and syndrome of wind-phlegm blocking collaterals ［HR=2.007， 95%CI（1.179-3.418）］ were found to be risk factors in middle-aged and elderly T2DM-SAP patients. Insulin ［HR=0.604， 95%CI（0.399-0.914）］， glycosidase inhibitor ［HR=0.627， 95%CI（0.409-0.962）］， and TCM treatment ［HR=0.328， 95%CI（0.214-0.503）］ were protective factors in middle-aged and elderly T2DM-SAP patients. The prediction model was constructed based on the above risk factors. The C-index of the model was 0.818 （95% CI 0.777 -0.859） in the training set and 0.814 （95% CI 0.773-0.855） in the validation set， and the change of C-index over time was plotted. The AUC of patients for 5， 10， 15 years in the training set was 0.71， 0.67， and 0.61. The AUC of patients for 5， 10， and 15 years in the validation set was 0.60， 0.68， and 0.63， respectively. The calibration map and clinical decision curves of 5， 10， 15 years were drawn in the training set and the validation set， respectively. The model was well calibrated and clinically effective. ConclusionThe history of cerebrovascular disease， LDL， dull red tongue， dull purple tongue， white thick coating， thin and weak pulse， and syndrome of wind-phlegm blocking collaterals are risk factors for MACCE in middle-aged and elderly T2DM-SAP patients， and insulin， glycosidase inhibitors， TCM treatment are protective factors for MACCE in middle-aged and elderly T2DM-SAP patients. A clinical prediction model is established accordingly. This model has good discrimination， calibration degree， and clinical effectiveness and provides a scientific basis for the prevention and treatment of MACCE in middle-aged and elderly T2DM-SAP patients.

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.
Animals ; Female ; Mice ; Azepines ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; MicroRNAs/genetics* ; RNA, Messenger ; Tumor Suppressor Protein p53/genetics* ; Humans ; Drug Resistance, Neoplasm

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg^-1) and high dose (10 mg·kg^-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.

OBJECTIVE: To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease. METHODS: The transplanted tumor was formed by subcutaneous injection of 2×10⁷ Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis. RESULTS: There were 2×10⁷ Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections. CONCLUSION The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.
Animals ; Body Weight ; Disease Models, Animal ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.
Animals ; High-Throughput Nucleotide Sequencing ; Humans ; Methylation ; Mice ; MicroRNAs/genetics* ; Oxidative Stress ; RNA, Small Interfering/metabolism* ; Real-Time Polymerase Chain Reaction

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an ¹⁸F-labeled MAGL inhibitor ([¹⁸F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [¹⁸F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl₄) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [¹⁸F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [¹⁸F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [¹⁸F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [¹⁸F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

Background: Obesity is associated with adverse health events among diabetic patients, however, the relationship between obesity fluctuation and risk of microvascular complications among this specific population is unclear. We aimed to examine the effect of waist circumference (WC) and body mass index (BMI) variability on the risk of diabetic microvascular outcome Methods: Annually recorded anthropometric data in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was used to examine the association of WC and BMI variability defined as variability independent of mean, with the risk of microvascular outcomes, including neuropathy, nephropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) (Trial registration: ClinicalTrials.gov., no. NCT00000620). Results: There were 4,031, 5,369, and 2,601 cases of neuropathy, nephropathy, and retinopathy during a follow-up period of 22,524, 23,941, and 23,850 person-years, respectively. Higher levels of WC and BMI variability were associated with an increased risk of neuropathy. Compared with the lowest quartile, the fully-adjusted HR (95% CI) for the highest quartile of WC and BMI variability for neuropathy risk were 1.21 (1.05 to 1.40) and 1.16 (1.00 to 1.33), respectively. Also, higher quartiles of BMI variability but not WC variability were associated with increased risk of nephropathic events. The fully-adjusted HR (95% CI) for the highest quartile compared with the lowest quartile of BMI variability was 1.31 (1.18 to 1.46). However, the results for retinopathic events were all insignificant. Conclusion Among participants with type 2 diabetes mellitus, WC and BMI variability were associated with a higher risk of neuropathic events, whereas BMI variability was associated with an increased risk of nephropathic events.

OBJECTIVE: To investigate the serum lipid levels and their prognostic significance in patients with multiple myeloma (MM). METHODS: A total of 87 newly diagnosed MM patients and 87 healthy controls in our hospital from January 2012 to April 2021 were selected. Serum lipid levels were compared between MM patients and healthy controls. The differences of serum lipid levels in patients among two groups of sex, age, hemoglobin (Hb), albumin (ALB), platelet (PLT), β₂-microglobulin (β₂-MG) and bone marrow plasma cell ratio (BMPC), different immune types, different ISS stages, before and after chemotherapy were analyzed. Univariate and COX multivariate regression analysis were used to analyze the influence of clinical parameters such as serum lipid indexes on prognosis of MM. RESULTS: The serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) in MM patients were significantly lower than those in healthy controls (P<0.05). Anemia, low protein and low PLT in patients were related to low cholesterol. The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with low Hb and ALB were significantly lower than those in patients with high Hb and ALB (P<0.05). The Apo B level of low PLT patients was significantly lower than that of high PLT patients (P<0.05). The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with different immune types were significantly different, the above indexes of IgA type were significantly lower than IgG type(P<0.05), IgG type were significantly lower than light chain type(P<0.05), double clone type were significantly lower than light chain type (P<0.05). The levels of TC, LDL-C, and Apo B in patients with different ISS stages were significantly different, stage Ⅱ were lower than those of stage Ⅰ (P>0.05), stage Ⅲ were significantly lower than those of stage Ⅱ and stageⅠ(P<0.05). The levels of TC, TG, LDL-C, HDL-C, Apo A1 and Apo B in patients after chemotherapy were significantly higher than those before chemotherapy (P<0.05). Univariate analysis showed that Hb, PLT, β₂-MG, BMPC, LDL-C and Apo B affected the prognosis of MM. Multivariate analysis showed that BMPC and Apo B were independent factors affecting the prognosis of MM. CONCLUSION The serum cholesterol level is decreased in MM patients, and hypocholesterolemia is related to the classification and staging of the disease. With the improvement of the disease, the serum cholesterol level is increased, and low serum Apo B level predicts a poor prognosis.
Apolipoprotein A-I ; Apolipoproteins B ; Cholesterol, HDL ; Cholesterol, LDL ; Humans ; Immunoglobulin G ; Multiple Myeloma ; Prognosis