ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

Objective: To compare and analyze the antibacterial effects of platelets against five common clinical pathogenic bacteria including MRSA, SE, SA, E. coli, and CRKP, and to preliminarily explore the role of DCD sensitivity in the observed variations of antibacterial effects. Methods: The same number of platelets were used to establish co-culture systems of platelets and platelet lysates with the five pathogenic bacteria. The antibacterial effects of platelets and platelet lysates on the five pathogenic bacteria were evaluated by observing the turbidity of the bacterial solution, measuring the OD value of the bacterial solution and counting the colonies. The supernatant protein of platelets co-cultured with MRSA was collected for quantitative proteomics analysis to explore the important antibacterial proteins of platelets. The content of DCD in the supernatant after co-culture of platelets and platelet lysates with the five pathogenic bacteria was detected by ELISA to preliminarily analyze the reasons for the different antibacterial effects of platelets on the five pathogenic bacteria. Results: Compared with the control group of MRSA, SA, and SE, the turbidity of the bacterial solution decreased after co-culture of platelets and platelet lysates with MRSA, SA, and SE for 12 h, and the OD value and colony count were significantly reduced (P<0.05). The turbidity of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with E. coli for 24 h, but the OD value decreased (P<0.05), and the colony count decreased to 10 CFU/mL but the difference was not statistically significant (P>0.05). Compared with the control group of CRKP, the turbidity, OD value, and colony count of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with CRKP (P>0.05). Proteomics results showed that after co-culture with MRSA, important proteins related to platelet activation, including collagen, fibrinogen, von Willebrand factor, integrin αIIbβ3, platelet glycoprotein V and IV were significantly up-regulated. ELISA results showed that after co-culture with the five pathogenic bacteria, platelets could secrete a large amount of DCD, with the content around 3 μg/mL. Conclusion: The antibacterial effect of platelets on Gram-positive bacteria MRSA, SA, and SE is better than that on Gram-negative bacteria E. coli and CRKP, and platelets have the best antibacterial effect on MRSA. The differences in antibacterial effects of platelets on the five pathogenic bacteria may be related to the sensitivity of DCD antibacterial peptides to the five pathogenic bacteria.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

Objective: To evaluate the therapeutic potential and underlying mechanisms of action of propolis in db/db mice. Methods: The chemical composition of propolis was analyzed using UHPLC-MS/MS. Thirty mice, including six wt/wt and 24 db/db mice, were randomly assigned to four groups (n = 6 per group): control, model, metformin (250 mg/kg), low dose propolis (100 mg/kg), and high dose propolis (HDP; 400 mg/kg). Treatments were administered orally for four weeks. Body weight and FBG levels were recorded weekly, and an oral glucose tolerance test was conducted on the 25th day. Serum levels of FIN, GSP, connecting peptide, AST, ALT, HDL, LDL, TG, and TC were quantified using ELISA. Liver histopathology was assessed using H&E and PAS staining. Western blotting was performed to examine the expression levels of NF-κB, phosphorylated NF-κB, IκBα, pIκBα, and AKT in liver tissues. Results: The top 10 metabolites of propolis were identified in positive and negative ion modes. The HDP group exhibited a significant reduction in FBG levels, body weight, connecting peptide levels, homeostatic model assessment of β-cell function scores, and homeostasis model assessment of insulin resistance scores (all P < .05). GSP levels were significantly reduced in both treatment groups (all P < .001). The HDP group also exhibited a reduction in TC and LDL levels (both P < .05), whereas HDL levels increased in both treatment groups (all P < .05). Liver weight, AST levels, and ALT levels were reduced in both treatment groups (all P < .05). Histological analysis revealed improved liver morphology. Protein analysis demonstrated downregulation of phosphorylated NF-κB and phosphorylated IκB, alongside upregulation of AKT. Conclusion Propolis exhibited significant antihyperglycemic effects in db/db mice, potentially by modulating the AKT and NF-κB signaling pathways, highlighting its potential as a therapeutic agent for diabetes management.

Objective To analyze the effects of three sterilization methods,namely,pressure steam,low-temperature plasma and ethylene oxide,on the magnetic flux of magnetic surgical devices and their sterilization costs.Methods A total of 234 magnetic surgical devices of different specifications and models(magnetic rings)were randomly divided into Group A,Group B and Group C after the paired number was labelled,and each group consisted of 78 pieces(39 pairs).After packaging each pair of devices according to sterilization specifications,Group A was sterilized by pressure steam,Group B was sterilized by low-temperature plasma,and Group C was sterilized by ethylene oxide.We measured the magnetic flux of three sets of magnetic rings before and after sterilization,and comparatively analyzed the sterilization cost and sterilization time of the single package.Results There was no statistically significant difference in the impact of the three sterilization methods on the magnetic flux of the magnetic surgical devices(P＞0.05),but there was a significant difference in the magnetic flux before and after sterilization for each sterilization method(P＜0.001);the sterilization cost was(1.96±0.16)yuan for Group A,(23.17±0.32)yuan for Group B,and(8.16±0.18)yuan for Group C,showing statistically significant differences among the three groups(P＜0.01).The sterilization time was(65.21±3.36)min for Group A,(45.46±1.39)min for Group B,and(1020.38±12.21)min for Group C,with statistically significant differences among the three groups(P＜0.01).Conclusion None of the three sterilization methods affects the magnetic flux of the magnetic surgical devices.Pressure steam method shows the lowest cost of single package,low-temperature plasma method shows the highest cost of single package,while ethylene oxide method shows the highest sterilization time.Pressure steam should be the preferred sterilization method for magnetic surgical devices.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Objective To explore the independent risk factors that affect the overall survival(OS)of elderly patients with hepatocellular carcinoma(HCC,≥60 years old)and build a nomogram prediction model.Methods Clinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database.In accordance with the inclusion and exclusion criteria,the screened patients were randomly assigned to a training group(70%)and a validation group(30%).The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis.On the basis of the determined variables,nomograms were developed and verified to predict the OS of elderly patients with HCC at 6,12,and 24 months.The consistency index(C index),calibration curve,receiver's operating characteristic(ROC)curve,and area under curve(AUC)were used to evaluate the prediction efficiency and discrimination ability of the prediction model,and decision curve analysis(DCA)was used to evaluate the potential clinical application value of the nomogram.Results A total of 1134 elderly patients with HCC were included,with 793 in the training group and 341 in the validation group.Seven variables,including age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy,were identified as independent prognostic factors of this population.The constructed nomogram shows excellent prediction performance,with C indices of 0.745 in the training group and 0.704 in the validation group.The AUC values of the training group at 6,12,and 24 months were 0.785,0.788,and 0.798,respectively,and those of the validation group were 0.780,0.725,and 0.607,respectively.The calibration curve shows good consistency from the predicted survival probability to the actual probability.The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability.Conclusion Age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy are important influencing factors for the survival of elderly patients with HCC.The prediction model of prognosis nomogram constructed in this study has good predictive value,and it can be used to predict the OS of elderly patients with HCC,which could be helpful for individualized survival assessment and clinical management of these patients.

Objective To explore clinical value of the expression levels of cell surface transmembrane glycoprotein molecule 44(CD44)mRNA,cell surface transmembrane glycoprotein molecule 24(CD24)mRNA,and protein in the placenta of severe preeclampsia(SPE)patients.Methods The SPE patients who were delivered by cesarean section in the Second People's Hospital of Liaocheng from June 2019 to June 2022 were further divided into 45 patients in early onset SPE group(gestational age≤34 weeks)and 55 patients in late onset SPE group(gestational age＞34 weeks)according to the different gestational age.The control group consisted of 100 normal cases in the same period.The expression of CD44 and CD24 in placenta of SPE patients was detected by fluorescent quantitative PCR and immunohistochemistry,Pearson method was used to analyze the difference of their expression levels and their correlation with the clinical characteristics of SPE disease,and multivariate logistic regression was used to analyze the influencing factors of SPE.Results Compared with the control group,the expression levels of CD44 mRNA(0.55±0.12 vs 1.02±0.33)and CD24 mRNA(0.68±0.19 vs 1.05±0.11)in SPE placental tissues decreased significantly,the differences were statistically significant(t=13.385,16.853,P＜0.05).The immunohistochemical staining results showed that CD44 and CD24 were mostly negative or weakly positive in the SPE group placental tissue,while they were mostly positive in the control group,the positive rates of CD44 and CD24 in the SPE placental tissue were lower than those in the control group,and the differences were statistically significant(χ2=9.696,14.346,P＜0.05).Compared to the early onset SPE group,the expression levels of CD44(0.65±0.17 vs 0.42±0.11)and CD24(0.77±0.23 vs 0.58±0.13)mRNA in placental tissue of late onset SPE were higher,and the differences were statistically significant(t=7.830,4.932,P＜0.05).Compared with the control group,the BMI,systolic blood pressure,diastolic blood pressure,urinary protein,Cr,LDH and BUN were significantly increased in SPE group(t=5.360～30.241,all P＜0.05).In SPE group,the gestational age was earlier,the MPV and ALB were lower,the newborn's birth length was shorter,and the body weight than control group,the differences were statistically great(t=3.232～11.109,all P＜0.05).The expression of CD44 and CD24 in SPE placenta was positively correlated(r=0.698,P＜0.05),the expression of CD44 in SPE placenta was positively correlated with CD24,gestational week of delivery,MPV and neonatal birth length(r=0.611,0.639,0.612,0.465,all P＜0.05),and was negatively correlated with systolic blood pressure,urinary protein and LDH(r=-0.604,-0.569,-0.593,all P＜0.05).The expression of CD24 was positively correlated with gestational age,MPV and newborn birth length(r=0.605,0.584,0.640,all P＜0.05),and was negatively correlated with systolic blood pressure,urinary protein and LDH(r=-0.637,-0.593,-0.561,all P＜0.05).The results of logistic regression analysis showed that MPV(95％CI:1.429～4.350),urinary protein(95％CI:1.529～2.709),and LDH(95％CI:1.425～3.932)were all independent risk factors for SPE(all P＜0.05).High levels of CD44(95％CI:0.561～0.940)and CD24(95％CI:0.495～0.814)were independent protective factors for SPE(P＜0.05).Conclusion The low expression levels of CD44 and CD24 in placenta of SPE patients are independent protective factors of SPE,which can provide direction for the follow-up treatment of SPE.

Objective·To investigate the effects of multiple sevoflurane exposures on the proliferation and differentiation of primary oligodendrocytes.Methods·Oligodendrocyte precursor cells(OPCs)were extracted from the cortex of rats on the day of birth and cultured in vitro.The cells were divided into control and sevoflurane groups.To simulate the clinical situation of sevoflurane exposure,cells in the sevoflurane group were exposed to 3%sevoflurane for 3 consecutive days,2 h for each time.After the OPCs were differentiated and matured,immunofluorescence staining and Western blotting were used to detect the expression of myelin basic protein(MBP)and the myelin-associated glycoprotein(MAG).Cell proliferation assays(BrdU and Ki67)and a cell viability assay(CCK8)were used to detect the effects of sevoflurane on the proliferation ability of OPCs and the survival rate of oligodendrocytes.Western blotting was used to detect the protein content of caspase-3.Lentiviral transfection technology was used to overexpress YTH N6-methyladenosine RNA binding protein F1(YTHDF1)in OPCs,and then CCK8 was used to detect cell proliferation and survival.Results·Immunofluorescence results showed that multiple sevoflurane exposures led to a decrease in the number of primary oligodendrocytes expressing mature myelin surface markers(MBP,MAG);Western blotting results showed that these exposures led to upregulation of caspase-3 expression in primary OPCs;CCK8 results showed that the survival rate of primary OPCs decreased with the increase in the number of sevoflurane treatments;however,BrdU and Ki67 staining results showed that the proliferation ability of primary OPCs was enhanced after sevoflurane exposure.In addition,overexpression of YTHDF1 could partially improve the decreased survival rate of primary OPCs caused by multiple sevoflurane exposures(all P<0.05).Conclusion·Multiple sevoflurane exposures impair the myelinating ability and survival rate of primary oligodendrocytes,manifested by apoptosis of some primary OPCs.In contrast,sevoflurane exposure compensatorily increases the proliferation ability of surviving primary OPCs.