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.

Objective To investigate the serum levels of microRNA-892b(miR-892b)and growth-associat-ed oncogene product β(GROβ)in patients with gastric cancer and their clinical significance.Methods A total of 124 patients with gastric cancer admitted to the hospital from February 2019 to February 2022 were select-ed as the gastric cancer group,and 100 volunteers with normal gastroscopy were selected as the control group during the same period.Serum levels of miR-892b and GROβ were detected in the two groups,and the rela-tionship between serum levels of miR-892b and GROβ and clinicopathological characteristics of patients with gastric cancer was analyzed.Multivariate Cox regression analysis was used to explore the influencing factors of prognosis of patients with gastric cancer.Results The serum level of miR-892b in gastric cancer group was lower than that in control group,and the serum level of GROβ was higher than that in control group(P＜0.05).There were statistically significant differences in serum miR-892b and GROβ levels in gastric cancer pa-tients with different degrees of differentiation,maximum tumor diameter lymph node metastasisand TNM stage(P＜0.05).A total of 124 patients with gastric cancer were followed up for one year after discharge,91 patients survived,and the overall survival rate was 73.39％.The one year overall survival rate of gastric cancer patients was related to the degree of differentiation,maximum tumor diameter,lymph node metastasis and TNM stage(P＜0.05).The overall survival rate of gastric cancer patients with high expression of serum miR-892b and low expression of GROβ was higher than that of patients with low expression of serum miR-892b and high expression of GROβ(P＜0.05).Multivariate Cox regression analysis showed poor differentia-tion(HR=1.839,95％CI 1.048-3.227),lymph node metastasis(HR=1.791,95％CI 1.076-2.982),TNM stage Ⅲ-Ⅳ(HR=1.660,95％CI 1.015-2.715),low expression of serum miR-892b(HR=3.040,95％CI 1.592-5.805),high expression of serum GROβ(HR=2.277,95％CI 1.503-3.451)were risk fac-tors for the prognosis of gastric cancer patients(P＜0.05).Conclusion The serum level of miR-892b is de-creased and the level of GROβ is increased in patients with gastric cancer,which is closely related to the occur-rence and development of gastric cancer.The expression of miR-892b and GROβ is related to the clinicopatho-logical characteristics and prognosis of patients,and can be used as a biological indicator to evaluate the prog-nosis of patients with gastric cancer.

Objective:To investigate effect of Yiqi Huoxue Huazhuo Jiedu Prescription(YHHJP)on inflammatory factors of brain tissues,tight junction between brain and colon tissues,intestinal flora and bacterial metabolites in cerebral ischemia reperfusion injury(CIRI)rats based on brain-gut axis.Methods:Fifty male SD rats of SPF grade were randomly divided into sham-operation group(Sham),model group(MCAO),low,medium,high doses YHHJP groups(TCM-L/TCM-M/TCM-H).Middle cerebral artery occlusion model was established according to Zea Longa methods.Neurological function defects were detected 3 days after administra-tion.TTC staining was used to calculate infarct size of brain tissue.Pathological changes of brain tissue were observed by Nissl staining,and pathological changes of brain and colon tissues were observed by HE staining.IL-1β,IL-6,TNF-α in brain tissue and LPS con-tent in serum were detected by ELISA,and D-LA content in serum was detected by biochemical method.Gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1,Claudin-1 in colon tissue were studied by Real-time fluorescent quantita-tive PCR.Intestinal flora were detected by 16S rDNA high-throughput sequencing.Results:Compared with Sham group,pathological damage of brain and colon tissue were serious in MCAO group,intestinal flora structure was significantly different,neural function im-pairment was aggravated,infarct size was increased,IL-1β,IL-6,TNF-α contents in brain tissue,and LPS,D-LA contents in serum were increased,gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1 and Claudin-1 in colon tissue were decreased significantly(P<0.05).Compared with MCAO group,pathological damage of brain and colon tissue of rats were relieved in TCM-L,TCM-M,TCM-H groups,disturbance of intestinal microflora microecology was improved,neurological function impairment and infarct size were markedly decreased,IL-1β,IL-6,TNF-α contents in brain tissue were decreased,gene expressions of ZO-1 and Claudin-1 in colon tissue were increased significantly(P<0.05);LPS and D-LA contents in serum were decreased in YH-HJP medium and high doses groups,while gene expressions of ZO-1 and Claudin-5 in brain tissue were increased significantly(P<0.05).Conclusion:YHHJP has a good effect on improving CIRI,whose mechanism may be related to regulating diversity of intestinal flora,reducing release of intestinal bacterial metabolites LPS and D-LA,increasing gene expressions of tight junction proteins ZO-1,Claudin-5 and Claudin-1,and down-regulating secretion of proinflammatory cytokine.

The pathogenesis of attention deficit and hyperactive disorder(ADHD)remains unclear.Evidence from epidemiological,biomarker,and genetic studies indicates that inflammation may play a crucial role in ADHD development.Inflammation can influence the onset and progression of ADHD through various mechanisms,such as activation of the hypothalamic-pituitary-adrenal(HPA)axis,alterations in neurotransmitter metabolism,maternal immune activation,disruption of the blood-brain barrier integrity,and impacts on neurodevelopment.A deeper understanding of the relationship between inflammation and ADHD could provide valuable insights into the pathophysiological mechanisms of ADHD and open new perspectives for clinical diagnosis and treatment.

Objective:To explore the changes of large-scale functional brain networks and network topological properties in patients with major depressive disorder (MDD) whose diagnosis had not changed after 5 years of follow-up.Methods:Totally 521 cases of hospitalized MDD patients were recruited from January 2012 to August 2018, and another 204 cases of gender- and age-matched healthy controls were recruited. All participants completed resting-state functional magnetic resonance scanning and clinical assessment. Their diagnosis were reviewed 5 years after discharge.A total of 258 participants whose diagnosis had not changed were counted into the MDD group for analysis. The differences in large-scale brain network connectivity between the two groups were analyzed by constructing a whole-brain functional network, on the basis of which the altered topological properties of the sensorimotor network (SMN), visual network (VN) and default mode network (DMN) were further analyzed between the two groups.The SPSS 24.0 software was used for data analysis and the independent sample t-test and χ2 test were used for the data comparison of the two groups. Results:Compared with the healthy controls, the MDD group had significantly decreased network clustering, mainly involving the SMN, VN and DMN (edge P<0.001, cluster P<0.05). The MDD group had decreased functional connectivity(FC) strength within the SMN, VN and DMN networks, the FC strength between the SMN and VN networks, between the frontoparietal network (FPN) and the DAN networks were decreased(all P<0.05, FDR corrected). Graph-theory analysis showed that local efficiency, clustering coefficient, and normalized shortest path length were decreased in the MDD group, node efficiency was decreased in the left ventral medial prefrontal cortex and the middle of the bilateral insula, node centrality was decreased in the middle of the bilateral insula and occipital lobe, and the betweenness was decreased in the middle of the right insula (all P<0.05, FDR corrected). Conclusion:MDD exhibits abnormal network functional connectivity, disruption of network topological properties, diminished optimal information processing, and to some extent reflects the severity of depressive symptoms. The decreased ability of information transfer flow in the insula plays an important role for the functional abnormality of the network.

Objective To explore the effects of wogonin on cognitive function and neuroinflamma-tion in VaD rats by regulating AMPK/SIRT1 pathway.Methods 90 VaD rats were randomly di-vided into model group,low-,medium-and high-dose wogonin groups(50,100,200 mg/kg),and high dose+AMPK inhibitor(20 mg/kg)group,18 animals per group.Another 18 normal rats served as sham operation group.ELISA was utilized to measure the contents of IL-1β,TNF-α and IL-6 in hippocampal tissues.Western blotting was conducted to detect the expression of Iba-1,p-AMPK,AMPK and SIRT1 in hippocampal tissues.Results Compared with the sham operation group,the model group had longer escape latency,and elevated contents of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression level of Iba-1 protein in hippocampal tissue,shorter stay time at original platform,and lower expression of p-AMPK/AMPK and SIRT1 in hippocampal tissues(P＜0.05).Treatment of three doses of wogonin,in a dose-dependent man-ner,reduced escape latency,and decreased levels of IL-1β,TNF-α and IL-6,number of Iba-1 posi-tive cells and expression of Iba-1 protein in hippocampal tissue,but longer stay time at original platform,and enhanced expression of p-AMPK/AMPK and SIRT1 protein in hippocampal tissue when compared with the model group(P＜0.05).The high dose+AMPK inhibitor group showed longer escape latency(47.64±5.39 s vs 26.45±3.27 s),shorter stay time at original platform(21.78±3.51 s vs 35.22±5.02 s),increased levels of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression of Iba-1 protein in hippocampal tissue,and lower expression levels of p-AMPK/AMPK and SIRT1 in hippocampal tissue when compared with the high-dose group(P＜0.05).Conclusion Wogonin may improve cognitive function and hippocampal tissue patho-logical damage in VaD rats by activating the AMPK/SIRT1 pathway,and inhibit neuroinflammation.

Immune checkpoint inhibitors(ICI),an immunotherapy,have an important role in the treatment of various cancers.However,ICIs induce several immune-related adverse events(irAEs).Interleukin(IL)-6 is an important inflammatory factor that promotes cancer progres-sion and modulates the clinical application of ICIs through various mechanisms.Herein,we postulate possible mechanisms that are involved in the ICI-regulatory effects mediated by the expression of the cytokine interleukin-6(IL-6),elucidate the effect of IL-6 on checkpoint-block-ade therapy and irAEs,and summarize the role of IL-6 signaling-targeted interventions in ICIs efficacy and irAEs management.

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.