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.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVE: To investigate the expression level and clinical significance of Wilms' tumor 1 (WT1) in bone marrow of patients with myelodysplastic syndromes (MDS). METHODS: The clinical data of 147 MDS patients who accepted real-time quantitative polymerase chain reaction (RT-PCR) to detect the expression level of WT1 in bone marrow before treated in Nanfang Hospital, Southern Medical University from January 2017 to April 2021 were retrospectively analyzed. According to the expression level of WT1, the patients were divided into WT1⁺ group and WT1^- group, their clinical characteristics and prognosis were analyzed. RESULTS: The positive rate of WT1 in 147 MDS patients was 82.3%. There were significant differences in bone marrow blast count, aberrant karyotypes, WHO 2016 classification, and IPSS-R stratification between WT1⁺ group and WT1^- group (all P<0.05). Furthermore, the higher the malignant degree of MDS subtype and the risk stratification of IPSS-R, the higher expression level of WT1. Compared with WT1^- group, there were no differences in overall survival (OS) time and the time of transformation to AML in WT1⁺ group (both P>0.05). In patients who did not accept transplantation, the median OS time of WT1⁺ patients was significantly shorter than that of WT1^- patients (P=0.049). Besides, regarding WT1⁺ group, patients who underwent transplantation had longer OS time and lower mortality than those who received hypomethylating agents (P=0.002, P=0.005). CONCLUSION WT1 expression level directly reflects the disease progression, and it is also associated with prognosis of MDS patients.
Bone Marrow/metabolism* ; Humans ; Myelodysplastic Syndromes/diagnosis* ; Prognosis ; Retrospective Studies ; WT1 Proteins/metabolism*

AIM: To explore the effects of inflammatory conditions on the pharmacokinetics of methotrexate (MTX) and its related mechanisms. METHODS: The model of adjuvant induced arthritis (AIA) was established. The expression of organic anion transporter 3 (OAT3) in kidney was detected by immunohistochemistry, Western blotting and QPCR. The plasma concentration of MTX was detected by LC-MS/MS, and the pharmacokinetics of MTX after different administration time were compared by isolated rat kidney perfusion, kidney slices, in vitro cell uptake and transport experiments. RESULTS: The expression of OAT3 was significantly increased in the kidneys of AIA rats by immunohistochemistry, Western blotting and QPCR. At the same time, the concentration of MTX was detected by the optimized LC-MS/MS. The results showed that the uptake of MTX in the kidney slices of AIA rats was significantly increased, and Pro could reduce the excretion of MTX by inhibiting OAT3. Furthermore, it was demonstrated in vitro that inflammatory pathology can promote renal excretion of MTX by increasing the expression and functional activity of OAT3.CONCLUSION: Under inflammatory pathological conditions, it can increase the expression of OAT3 in the kidney, enhance its functional activity, accelerate the uptake of MTX by the kidney, and promote the excretion of MTX.

Objective To explore the effect of imiquimod (IMQ) on the proliferation of glioma U87 cell line U87. Methods U87 cells were divided into control group, 1 mmol/L I mmol/L MQ group, 5 mmol/L IMQ group, 1 mmol/L IMQ+ STAT3 inhibitor(STAT3-IN) group and 5 mmol/L IMQ + STAT3-IN group. To detect the number of 5-ethynyl-2 ' - deoxyuridine(EdU) -labeled cells or proliferation absorbance(A) values in each group by EdU and MTT assays. Interleukin (I L) - 6 mRNA, tumor necrosis factor (TNF) -a mRNA and protein content in U87 cells of each group were detected by Real-time PCR or ELISA. Western blotting was used to detect the protein expression of STAT3, phosphorylated STAT3 (p - S T A T 3), nuclear factor (N F) -KB and phosphorylated NF-KB (p-NF-KB) in U87 cells of each group. Results Compared with the control group, the number of EdU-labeled cells and absorbance values of U87 cells were successively decreased in 1 mmol/L IMQ group and 5 mmol/L IMQ group, showing a dose-dependent manner (P < 0 . 0 1, n— 1 0) . However, the number of EdU-labeled cells and the A values in IMQ + STAT3-IN group and 5 mmol/L IMQ + STAT3-IN group were significantly reduced. Compared with the control group, the protein expression of STAT3, p-STAT3, N F - K B, P ~ N F - K B, IL-6 and TNF-a were continuing low level in U87 cells of 1 mmol/L IMQ group and 5 mmol/L IMQ group (P < 0 . 0 1, * = 1 0) . As well as in 1 mmol/L IMQ + STAT3-INgroup and 5 mmol/L IMQ + STAT3-IN group, the proteins of above were low expressed (P < 0 . 01, n— 10) . Conclusion Imiquimod decreased the contents of IL-6 and TNF-a by down-regulating S T A T 3 / N F - K B pathway, and thus inhibited the proliferation of U87 cells.

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.
Bilirubin ; China ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Hyperbilirubinemia, Neonatal ; Infant, Newborn ; Retrospective Studies

Objective To select and develop a SNP-STR multiplex amplification system with genetic markers compatible with current STR databases. To understand its genetic polymorphisms in Sichuan Han population and its application value in DNA mixture analysis. Methods Based on the STR genetic markers in commercial kits, SNPs adjacent to these STR markers were selected to be SNP-STR genetic markers. A SNP-STR multiplex amplification system with genetic markers based on allele-specific amplification was constructed using allele-specific amplification primers. The genetic polymorphism of the system in the Sichuan Han population was investigated and the efficiency of systems with different numbers of loci to detect the two individual DNA mixture samples was evaluated. Results An allele-specific multiplex amplification system constituted of 13 SNP-STR genetic markers was selected and constructed. In Sichuan Han population, the heterozygosity of each locus ranged from 0.76 to 0.88, and the combined discrimination power reached 0.999 999 999 999 999 968. In the analysis of the two individual DNA mixture samples： for single-locus amplification, the genotype of the minor components can still be detected when the mixture ratio reaches 1 000∶1; for multiple loci multiplex amplification, the maximum mixture ratio can reach 500∶1. As the number of loci in the system increased, the detection efficiency of the minor components in the DNA mixture decreased. Conclusion SNP-STR genetic markers have a higher polymorphism than STR. The multiplex amplification system made of SNP-STR genetic markers has a better analysis efficiency for mixed samples than traditional STR multiplex amplification system.
China ; DNA Fingerprinting ; DNA Primers ; Gene Frequency ; Genetic Markers ; Humans ; Microsatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

OBJECTIVETo evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.

METHODSA randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed.

RESULTSNo patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05).

CONCLUSIONPatients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

OBJECTIVETo investigate the autophagy activity changes of umbilical cord mesenchymal cells (MSC) under hypobaric hypoxia and the effect of hypobaric hypoxia on cell viability.

METHODSUmbilical cord mesenchymal cells were cultured in the chamber of hypobaric hypoxia with an air pressure of 41.1 kPa and an oxygen density of 1%. At 0, 4, 8, 16, 24 and 48 hours, the cells were harvested for Western blot and real-time PCR to observe the expression level of the autophagy marker protein LC3B. And the cell viability under hypobaric hypoxia was evaluated after treatment with autophagy inhibitors HCQ (8 μg/ml) and 3MA (5 mmol/L).

RESULTSLC3B expression in MSC at protein and mRNA levels were up-regulated significantly after being cultured under hypobaric hypoxia condition for 8 hours. And compared with the control group, inhibition of autophagy reduced cell viability while increased Caspase-3 expression and the incidence of apoptosis.

CONCLUSIONHypobaric hypoxia activates autophagy in MSC, and the activation of autophagy might play a protective role for cell survival.