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.

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC₅₀ = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective To investigate the effect of XMD17-109 on the viability of glioma cells and its molecular mechanism based on extracellular signal-regulated kinase 5(ERK5)/inositol 1,4,5-trisphosphate receptor-interacting protein(ITPRIP)signaling pathway.Methods U251 glioma cells were routinely cul-tured,and ERK5 activity was inhibited by XMD17-109.ERK5 knockdown and ERK5 overexpression models were constructed by transfection of RNA fragments and plasmids,respectively.Cells were divided divided into the XMD17-109 group,the Control group,the siERK5 group,the siNC group,siERK5-OE group,the Vector group,the ERK5-OE+XMD17-109 group and the Vector+XMD17-109 group.The cell viability was detected by CCK-8,scratch and flow cytometry experiments and so on.The mRNA and protein expression levels of ERK5 and ITPRIP were detected by reverse transcription-quantitative real time PCR(RT-qPCR)and West-ern blot.Results Compared with the Control group,the cell viability of the XMD17-109 group decreased,and the expression level of ITPRIP decreased(P＜0.05).Compared with the siNC group,the cell viability of the siERK5 group was decreased,and the expression level of ITPRIP was decreased(P＜0.05).Compared with the Vector group,the cell viability of the ERK5-OE group was enhanced,and the expression level of ITPRIP was increased(P＜0.05).Compared the with Vector+XMD17-109 group,the cell viability of the ERK5-OE+XMD17-109 group was enhanced,and the expression level of ITPRIP was increased(P＜0.05).Conclusion XMD17-109 can inhibit the viability of glioma cells by inhibiting ERK5/ITPRIP signaling pathway,which is expected to be a potential drug for glioma treatment.

Isovaleric acidemia is a type of organic acidemia for which the earliest definite diagnosis was attained. It features an autosomal recessive inheritance, with the onset of age varying from newborn to adulthood. The clinical manifestations are complex and variable, which include feeding difficulty, vomiting, lethargy, coma, metabolic acidosis, sweaty feet odor and mental retardation. The mortality and mobility rates of isovaleric acidemia are quite high, and early diagnosis and rational treatment can significantly improve the prognosis. This article has provided a summary for the current understanding and research progress on isovaleric acidemia.
Adult ; Amino Acid Metabolism, Inborn Errors/genetics* ; Humans ; Infant, Newborn ; Isovaleryl-CoA Dehydrogenase/genetics*

Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.

Objective:To observe the effect of tenofovir disoproxil fumarate (TDF) antiviral therapy on HBV-specific CD8 +T cell function in peripheral blood of patients with HBeAg-positive chronic hepatitis B, and to assess its correlation with HBeAg sero-negativeness. Methods:Sixty-three cases with HLA-A02 restricted HBeAg-positive chronic hepatitis B who received TDF (300 mg/d) antiviral therapy were enrolled from October 2016 to July 2018. The peripheral blood CD8 +T cells were separated at baseline and 48 weeks after treatment. The peripheral blood T cells count were detected by flow cytometry. The frequency of HBV-specific CD8 +T cells secreting perforin, granzyme B, and interferon-γ (IFN-γ) were detected by enzyme-linked immunoblotting test. Direct and indirect contact co-culture system was established between HBV-specific CD8 +T cells and HepG2.2.15 cells. HBV DNA was detected in the culture supernatant. Target cell mortality was calculated by lactate dehydrogenase level. Cytokines expression was detected by enzyme-linked immunosorbent assay. Virus-specific CD8 +T cells cytokilling and non-cytokilling functions were evaluated. Measurement data of the two groups were compared by t-test or paired t-test. Results:Viral response, biochemical response, and HBeAg seroconversion rate at 48 weeks of TDF treatment were 100%, 90.48% (57/63), and 25.40% (16/63), respectively. There was no statistically significant difference in peripheral blood T cell count when compared with baseline and control group at 48 weeks of TDF treatment ( P > 0.05). At 48 weeks of TDF treatment, the frequency of HBV-specific CD8 +T cells secreting perforin, granzyme B, and IFN-γ in CHB patients was significantly higher than baseline ( P < 0.001). Furthermore, the frequency of HBV-specific CD8 +T cells secreting perforin, granzyme B, and IFN-γ was also significantly higher in CHB patients with HBeAg negative than that of non-negative ( P < 0.05). HBV-specific CD8 +T cells had induced significant down-regulation of HBV DNA in the supernatant of HepG2.2.15 cell culture ( P < 0.001) and remarkable IFN-γ and interleukin-2 secretion ( P < 0.05) at 48 weeks of TDF therapy in direct and indirect contact co-culture system. However, HepG2.2.15 cells death rate induced by virus-specific CD8 +T cells was increased only in the direct contact co-culture system (21.7% ± 6.18% vs. 16.1% ± 4.15%, P < 0.001). Compared with HBeAg non-negative patients, HBeAg negative CHB patients with HBV-specific CD8 +T cells had induced a strong decrease in HBV DNA ( P < 0.001) and an increase in IFN-γ secretion level ( P < 0.05). However, the target cell death proportion difference between HBeAg negative and non-negative patients was not statistically significant ( P > 0.05). Conclusion:During TDF treatment, with the viral load reduction, virus-specific CD8 +T cells cytokilling and non-cytokilling functions are significantly enhanced, and are closely related to HBeAg negative.

OBJECTIVE: To explore effects of different delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots (DBS), so as to provide evidence for improving accurate and reliable detection by tandem mass spectrometry. METHODS: A total of 1 254 616 newborn DBS samples in Newborn Screening Center of Zhejiang Province were delivered and stored at room temperature (group A, RESULTS: The concentrations of amino acids and carnitines in the three groups were skewed, and the differences in amino acid and carnitine concentrations among groups were statistically significant (all CONCLUSIONS Cold-chain logistics system and storage in low temperature and low humidity can effectively reduce degradation of some amino acids and carnitines in DBS, improve the accuracy and reliability of detection, and thus ensures the quality of screening for neonatal metabolic diseases.
Amino Acids/analysis* ; Carnitine/analysis* ; Dried Blood Spot Testing/standards* ; Humans ; Humidity ; Infant, Newborn ; Neonatal Screening ; Reproducibility of Results ; Specimen Handling/standards* ; Tandem Mass Spectrometry ; Temperature ; Time Factors

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Betacoronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Single-Cell Analysis