Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

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.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective:To investigate the clinical efficacy of anal dimple anorectoplasty on female infants with congenital anal atresia combined rectal vestibular fistula.Methods:Clinical data of 69 female infants with congenital anal atresia combined rectal vestibular fistula admitted to Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from July 2012 to July 2022 were retrospectively analyzed.They were divided into 2 groups according to the surgical methods: 34 cases of anal dimple anorectoplasty(group A) and 35 cases of anterior sagittal anorectoplasty(group B). The operation time, length of stay, short-term complications, long-term complications and bowel function (determined by the Rintala score at 6 months postoperatively) of the two groups were compared.The difference in the incidence of postoperative complications between groups was compared by Chi- square test, and the remaining differences between groups were compared by the paired t-test. Results:The operative time [(80.18±9.29) min vs.(103.85±8.26) min] and postoperative hospital stay[(6.10±1.52) d vs.(7.63±2.40) d] in group A were significantly shorter than those of group B ( t=11.40, 2.62; all P<0.05). The Rintala total score at 6 months postoperatively in group A was significantly higher than that of group B[(19.36±0.93) points vs.(18.76±0.44) points]( t=3.20, P<0.05). There were no significant differences in the incidences of short-term [(4/34, 11.8%) vs.(7/35, 20.0%)] and long-term complications [(2/34, 5.9%) vs.(4/35, 11.4%)]between group A and group B ( χ2=0.75, 0.75; all P>0.05). Conclusions:Anal dimple anorectoplasty for female infants with congenital anal atresia combined rectal vestibular fistula is safe and effective.

Humans ; Transcranial Magnetic Stimulation ; Pain Management ; Psychotic Disorders/therapy* ; Depressive Disorder, Major ; Treatment Outcome ; Transcranial Direct Current Stimulation

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

Tumors provide materials and energy for themselves through glucose metabolic reprogramming to meet the needs of their rapid growth. Studies have shown that a variety of metabolic enzymes and signal molecules involved in glucose metabolism play an important role in tumorigenesis and development, and are considered to be important targets for the diagnosis and treatment of malignant tumors. The detection technology based on tumor glucose metabolism has been widely used in basic research and clinical diagnosis and treatment of tumor. This paper summarizes the characteristics, driving factors and key regulatory targets of tumor glucose metabolism, and the detection techniques and functions of tumor glucose metabolism from the aspects of basic medical research and clinical diagnosis and treatment.

【Objective】 To investigate the effects and potential mechanisms of neurodegenerative lesions in male mice caused by ozone exposure. 【Methods】 We divided 23 C57BL/6N male mice aged 8 to 9 months into control group （clean air group， 11） and ozone group （1 mg/m ³， 4h/d， 12）. After 8 weeks of continuous ozone exposure， the Morris water maze experiment was used to detect the mice’s learning and memory ability， HE dyeing to observe pathological changes in hippocampal tissue cells， and immunoprinting tests to detect the expression levels of Tau， p-Tau and α-synuclein proteins in the cerebral cortex tissue. 【Results】 After 8 weeks of ozone exposure， the mice’s spatial learning and memory ability were impaired to a certain extent， the incubation period decreased with time， and the two lines were separated， but the difference was not statistically significant. Ozone exposure caused changes in the morphology of the mice’s hippocampal tissue cells， disorders in the arrangement of hippocampal neuron， and nuclear wrinkles， and significantly increased levels of p-Tau and α-synuclein protein expressions in cerebral cortex tissues （P<0.01）， but there was no statistical significance in the total Tau expression level. 【Conclusion】 Ozone exposure leads to the loss of learning and memory in mice， changes in hippocampal neurocellular pathology， and increased expression levels of neurodegenerative variable-related proteins.

Objective:To evaluate the role of hemopexin (HPX) in cerebral ischemia-reperfusion (I/R) injury in rats.Methods:One hundred and twenty healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 250-280 g, were divided into sham operation group (S group, n=36), cerebral I/R group (I/R group, n=36), vehicle group (V group, n=24), and HPX group ( n=24). The model of cerebral I/R injury was established by 120 min middle cerebral artery occlusion followed by reperfusion in anesthetized rats.At 6, 12 and 24 h of reperfusion, 4 rats in S group and I/R group were sacrificed, and the ischemic penumbra of the ipsilateral cerebral cortex was obtained to detect the expression of HPX by Western blot.In I/R, V and HPX groups, 0.9% normal saline 10 μl, 0.1% NaN 3 10 μl, and 1.86 mg/ml HPX 10 μl were injected into the lateral ventricle, respectively, immediately after reperfusion.Eight rats in each group were selected, and neurological deficit was scored at 1-7 days of reperfusion.Eight rats in each group were sacrificed at 1 and 7 days of reperfusion, brains were removed, and brain tissues were obtained for measurement of infarct size, and the percentage of infarct size was calculated. Results:Compared with S group, the expression of HPX in cerebral ischemic penumbra was significantly up-regulated at 24 h of reperfusion in I/R group, and the neurological deficit scores were significantly decreased at 1-7 days of reperfusion, and the percentage of cerebral infarct size was increased at 1 and 7 days of reperfusion in I/R, V and HPX groups ( P<0.05). Compared with I/R group, the neurological deficit scores were significantly increased at 1-7 days of reperfusion, and the percentage of cerebral infarct size was decreased at 1 and 7 days of reperfusion in HPX group ( P<0.05), and no significant change was found in the above indicators in V and I/R groups ( P>0.05). Conclusion:Up-regulation of HPX expression is the endogenous protective mechanism of cerebral I/R injury in rats.

Objective:To summarize the current policies and measures in curbing health corruption in China, and to evaluate the implementation results of these policies and measures.Methods:We made a systematic review to search and screen the literatures, with related thematic information extracted, compared and classified to form an integrated view by the data integration method of thematic synthesis.Results:A total of 147 literatures were included, covering such health policies and measures as the basic drug system, the centralized bidding and purchasing and centralized drug purchasing, the " two-invoice system" , hospital information disclosure system, adverse records of commercial bribery, doctor′s virtue evaluation system and no bribery agreement. These five policies and measures prove effective in curbing the corruption, but some types of corruption tend to evade such restrictions.Conclusions:The five types of policy measures summarized in the study have effectively curbed the high risk exposure of corruptions found in drugs, medical consumables and medical devices, and also guided and restrained the profit-oriented behaviors of the behavior subjects. Stronger measures should be integrated into a broader reform of the healthcare system, in combination with institutional compensation and operational mechanism reform, medical personnel compensation and incentive system, and modern pluralistic governance reform. Meanwhile, studies in the field of corruption need to focus on the direct and indirect effects of multi-level medical reform policies on corruption governance from an integrated perspective, while attention needs to cover more types of corruption behaviors, and to diversify research methods, so as to provide more practical policy support.