Objective To investigate the relationship between polymorphism of resistin(RETN)gene and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients in middle and high altitude areas.Methods A total of 400 patients with T2DM in Qinghai area were recruited and divided into simple T2DM group(T2DM,n=200)and T2DM combined with MAFLD group(T2DM+ MAFLD,n=200)according to liver ultrasonography.Healthy individuals confirmed by physical examination were selected as the normal control group(NC,n=180).Plasma resistin levels were measured by ELISA.The polymorphism of RETN-420C/G and +299G/A genes were detected by PCR sequencing.Results By comparing the polymorphism of RETN-420C/G gene in each group,it was found that the frequencies of G/G genotype and G allele frequency in T2DM+MAFLD group were higher than those in NC group and T2DM group(P<0.05),while the frequencies of C/C genotype and C allele frequency were lower than those in NC group and T2DM group(P<0.05).The risk of MAFLD increased by 1.571,2.126 and 1.537 times respectively in T2DM patients with C/G,G/G genotype and G allele.Logistic regression analysis showed that G/G genotype was a risk factor for MAFLD in T2DM patients.By comparing the polymorphism of RETN+299G/A gene in each group,it was found that A allele frequency in T2DM+MAFLD group was higher than that in NC group and T2DM group,while G allele frequency was lower than that in NC group and T2DM group(P<0.05).The allele A increased the risk of MAFLD in T2DM patients by 1.432 times compared to allele G.Conclusion RETN gene-420C/G locus G/G genotype increases the risk of T2DM combined with MAFLD in middle and high altitudeareas.

Objective To investigate the clinicopathological characteristics of radioactive Iodine-refrac-tory differentiated thyroid cancer(RAIR-DTC)to provide a clinical evidence for early prediction of the thyroid cancer patients with radioactive Iodine-refractory(RAIR).Methods The data of 84 patients with undergoing thyroidectomy and 131I therapy in PLA 960 hospital from January 2010 to December 2019 were retrospectively analyzed.Thirty-nine patients with diagnosed RAIR-DTC served as the study group and 45 cases of radioactive iodine-avid differentiated thyroid cancer(RAIA-DTC)served as the control group.The clinicopathological characteristics were compared between the two groups.The logistic regression was used to analyze the inde-pendent risk factors of RAIR-DTC,and the RAIR-DTC prediction model was established.Results Compared with the RAIA-DTC group,the RAIR-DTC group had more iodine treatment times,the proportions of the pa-tients with age ≥55 years old,total iodine therapeutic dose,distant metastasis,TNM stage Ⅳ,high-risk sub-types and focal calcification were higher,the tumor maximum diameter was greater,the number of lymph node metastases was more and the probability of Ⅱ,Ⅰ+Ⅱ and non-central lymph node metastases was higher(P＞0.05).The progression-free survival rate had statistical difference between the two groups(P＜0.05).The total survival rate had no statistical difference between the two groups(P＞0.05).The binary logistic re-gression analysis results showed that the distant metastasis,high-risk histological subtype and maximum tumor diameter ≥10.5 mm were the independent risk factors for RAIR-DTC.The obtained fitting equation logit(P)=-2.259+3.330X1+2.287X2+1.606X3,the ROC curve was used to calculate the truncation val-ue of the fitted equation as-0.312 5,when logit(P)＞-0.312 5,it might develop into RAIR-DTC.Conclusion The clinicopathological characteristics of the patients with differentiated thyroid cancer could ef-fectively predict RAIR.

[Objective]To investigate the clinical features and high risk of very preterm infants with late-onset bacteri-al sepsis,so as to propose feasible prevention and treatment suggestions.[Methods]Totally 94 very preterm infants with late-onset bacterial sepsis from the Neonatology Department of Women's Hospital of Jiangnan University were recruited from February,2012 to January,2024.Their clinical data,including the perinatal situation,clinical symptoms,patho-gens,risk factors and treatment,were collected and analyzed.[Results]The incidence rate of very preterm infants with late-onset bacterial sepsis were 8.40 for 100 live birth babies.The major pathogens of the infections among these very pre-mature infants included gram-positive bacteria(71.1%).Logistic regression analysis showed that long term(≥7 d)use of antibiotics,invasive mechanical ventilation,indwelling central venous catheter(≥7 d),and vaginal delivery were high risk factors of very preterm infants with late-onset bacterial sepsis,the relative risk(OR)values were 2.787,4.243,3.033 and 2.174,respectively.[Conclusion]The gram-positive bacteria are the main pathogens of late-onset bacterial sepsis in very preterm infants.Long term(≥7 d)use of antibiotics,invasive mechanical ventilation,indwelling central ve-nous catheter(≥7 d)and vaginal delivery are high risk factors of very preterm infants with late-onset bacterial sepsis.The incidence of late-onset bacterial sepsis in very preterm infants can be reduced by strengthening perinatal management,shortening the time of antibiotic application and reducing invasive operations.

Objective:To analyze the efficacy of metformin combined with paclitaxel injection in the treatment of patients with endometrial carcinoma and the influence on tumor markers.Methods:Eighty patients with endometrial cancer admitted to the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from January 2022 to June 2023 were retrospectively selected as the study objects, 40 of whom received chemotherapy with paclitaxel injection combined with carboplatin regimen (control group), and 40 received chemotherapy with metformin combined with paclitaxel injection and carboplatin regimen(observation group). The clinical efficacy, tumor markers, serum indicators and immune function indexes of the two groups were compared after 3 cycles of treatment.Results:After treatment, the total effective rate in the observation group was higher than that in the control group: 60.00%(24/40) vs. 37.50%(15/40), there was statistical difference ( χ2 = 4.05, P<0.05). After 3 cycles of treatment, the levels of human epididymal protein, cancer antigen 125, vascular endothelial growth factor, insulin-like growth factor 1 and hypoxia-inducible factor 1α in the observation group were lower than those in the control group: (27.05 ± 5.11) pmol/L vs. (33.96 ± 5.86) pmol/L, (24.11 ± 5.41) μg/L vs. (31.80 ± 5.53) μg/L, (215.68 ± 20.22) ng/L vs. (250.33 ± 20.19) ng/L, (170.33 ± 35.60) × 10 3 kU/L vs. (216.25 ± 41.72)×10 3 kU/L, (116.50 ± 20.17) ng/L vs. (147.77 ± 21.53) ng/L; the levels of glutathione peroxidase 1, cytotoxic T lymphocytes, natural killer cells and helper T lymphocytes in the observation group were higher than those in the control group: (271.63 ± 25.11) AU vs. (155.83 ± 22.60) AU, 0.25 ± 0.03 vs. 0.21 ± 0.02, 0.29 ± 0.03 vs. 0.23 ± 0.02, 0.41 ± 0.03 vs. 0.33 ± 0.04, there were statistical differences ( P<0.05). Conclusions:The combination of metformin, paclitaxel injection and carboplatin regimen in patients with endometrial cancer can improve the clinical efficacy, downregulate tumor marker expression, and improve serum oncological indicators, reducing immune damage.

As a secondary preventive measure for patients with coronary heart disease, cardiac rehabilitation can improve their quality of life and reduce mortality. One key aspect is to ensure that patients receive sufficient information. This article provides a review of the content, influencing factors, and support strategies for the cardiac rehabilitation information needs of patients with coronary heart disease, in order to provide reference for establishing a secondary prevention strategy for patients with coronary heart disease guided by information needs.

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.

"Toxicity Testing in the 21st Century—A Vision and Strategy"proposed by the National Research Council of US has brought innovative directives and objectives for toxicity evaluation and risk assessment,pushing forward the next generation of toxicity testing and risk assessment.In this initiative,the concept of adverse outcome pathways(AOPs)has emerged as a prominent methodology,capturing the attention of toxicologists and researchers due to its promising applications in recent years.The quantitative AOP(qAOP)is an extension of the adverse outcome pathway,which is built upon the foundational qualitative adverse outcome pathway model and leverages mathematical frame-works to depict dose-response and/or response-response relationships.This article reviews the princi-ples and advancement surrounding qAOP,introduceds two prevalent methodologies for constructing qAOP,Bayesian network models and regression models,and demonstrates diverse applications of qAOP.Actual cases are used to underscore the transformative role of qAOP in contemporary toxicology and risk assessment practices.

Purpose To explore the feasibility of using virtual non-contrast images derived from spectral CT for pulmonary angiography(CTPA)to replace true non-contrast scan of chest,in order to reduce radiation dose.Materials and Methods Fifty-six patients undergoing CTPA examination in the First Affiliated Hospital of Dalian Medical University were prospectively enrolled.All patients underwent both conventional chest CT and spectral CTPA scan.On both virtual unenhanced images and true unenhanced images,CT values and standard deviation values of the pulmonary parenchyma in the level of thoracic aorta,main pulmonary artery,erector spine,as well as pulmonary apex,tracheal carina,and lung base were measured.Signal noise ratio and contrast noise ratio of thoracic aorta and pulmonary artery were calculated.The image quality and iodine residue of the two groups was evaluated.The consistency of subjective scores was also assessed.Dose length product,CT dose index volume and contrast agent dosage were recorded.The CT value,signal noise ratio,contrast noise ratio,radiation dose and subjective score of each region of interest in true unenhanced and virtual unenhanced images were compared.Results The inter-observer subjective scores were consistent(Kappa=0.984-0.992,P＜0.05).The subjective scores of the chest true unenhanced and virtual unenhanced images were 4.75±0.65 and 4.65±0.49,respectively,with no statistical difference(t=0.630,P=0.437).There was no significant difference in CT values of thoracic aorta,pulmonary artery and lung tissues between true unenhanced and virtual unenhanced images(P＞0.05).There was no significant difference in signal noise ratio and contrast noise ratio between pulmonary artery and thoracic aorta(P＞0.05).Replacing conventional chest scan with virtual unenhanced images of CTPA reduced the radiation dose by approximately 55％,reducing from(7.27±1.74)mSv to(3.26±0.84)mSv.Conclusion It is feasible to use CTPA virtual non-contrast images to replace conventional unenhanced CT chest imaging for lung disease screening,since it can significantly reduce the radiation dose to patients.

Background: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. Objectives: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,Ocarboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. Methods: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. Results: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis.In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. Conclusions This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.

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*