BACKGROUND: Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC. METHODS: RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database. RESULTS: The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members. CONCLUSIONS TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/mortality* ; Prognosis ; Gene Expression Regulation, Neoplastic ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*

The HACEK group microorganisms(Haemophilus parainfluenzae,Aggregatibacter actinomycetem-comitans,Cardiobacterium spp.,Eikenella corrodens,Kingella kingae)belong to Gram-negative bacilli and are members of the normal oropharyngeal microbiota,which can cause invasive opportunistic infection when the host immune barrier is damaged,with infective endocarditis being one of the most serious diseases.HACEK endocarditis is characterized by an insidious course,prolonged delay of diagnosis,and dependence on third-generation cephalo-sporins for treatment.In recent years,with the emergence and development of 16S ribosomal RNA gene sequencing technique,the rapid diagnosis of this disease is expected to be achieved.This paper summarizes the main clinical characteristics and research progress of infective endocarditis caused by HACEK group bacteria,aiming to provide reference for clinical diagnosis and treatment.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective:To evaluate value of CT perfusion in evaluating the efficacy of different vascular reconstruction methods in the treatment of adult ischemic moyamoya disease.Methods:The clinical data of 80 adult patients with moyamoya disease with ischemic blood type who received revascularization in the Affiliated Hospital of Jining Medical University from February 2019 to February 2023 were retrospectively analyzed, including 43 patients who received superficial temporal arterio-middle cerebral artery anastomosis (direct group) and 37 patients who received brain-dural arterio-artery vascularization (indirect group). The improvement of clinical symptoms, Modified Rankin Scale (mRS) Score, collateral vessels and CTP parameters were compared between the two groups.Results:The improvement of clinical symptoms in the direct group was better than that in the indirect group ( P<0.05), and the significant remission rate was significantly higher than that in the indirect group [86.0%(37/43) vs 59.5%(22/37), χ 2=7.262, P=0.007]. The postoperative mRS score in the direct group was significantly lower than that before surgery [0(0, 1) vs 1(1, 2), Z=5.550, P<0.001]. The score of mRS After surgery in the indirect group was significantly lower than that before surgery [0(0, 1) vs 1(1, 2), Z=4.281, P<0.001], but there was no statistically significant difference between the two groups ( P>0.05). There was no significant difference in digital subtraction angiography (DSA) collateral vessel formation between the two groups ( P>0.05). The CTP parameters of the two groups before and after surgery were consistent between observers and within observers [intraclass correlation coefficient (ICC) range 0.88-0.94]. In the operation area, the relative cerebral blood flow (rCBF) after surgery was significantly increased, and the relative time to peak (rTTP) and relative mean transit time (rMTT) were significantly decreased in both groups, with statistical significance ( P<0.05). In the ipsilateral basal ganglia and frontal lobe, rCBF in the direct group was significantly increased, rTTP and rMTT were significantly decreased, and the differences were statistically significant (all P<0.05), while there were no statistically significant differences in parameters in the indirect group (all P>0.05). The changes of rCBF, rTTP and rMTT in the operative area in the direct group were better than those in the indirect group, and the changes of rCBF, rTTP and rCBF in the basal ganglia and frontal lobe were better than those in the indirect group, with statistical significance (all P<0.05), while there were no statistically significant differences in the remaining parameters (all P>0.05). Conclusions:CT perfusion is of great value in evaluating the difference of clinical symptom improvement in the treatment of adult ischemic moyamoya disease with different vascular reconstruction methods.

The HACEK group microorganisms(Haemophilus parainfluenzae,Aggregatibacter actinomycetem-comitans,Cardiobacterium spp.,Eikenella corrodens,Kingella kingae)belong to Gram-negative bacilli and are members of the normal oropharyngeal microbiota,which can cause invasive opportunistic infection when the host immune barrier is damaged,with infective endocarditis being one of the most serious diseases.HACEK endocarditis is characterized by an insidious course,prolonged delay of diagnosis,and dependence on third-generation cephalo-sporins for treatment.In recent years,with the emergence and development of 16S ribosomal RNA gene sequencing technique,the rapid diagnosis of this disease is expected to be achieved.This paper summarizes the main clinical characteristics and research progress of infective endocarditis caused by HACEK group bacteria,aiming to provide reference for clinical diagnosis and treatment.

Objective:To evaluate value of CT perfusion in evaluating the efficacy of different vascular reconstruction methods in the treatment of adult ischemic moyamoya disease.Methods:The clinical data of 80 adult patients with moyamoya disease with ischemic blood type who received revascularization in the Affiliated Hospital of Jining Medical University from February 2019 to February 2023 were retrospectively analyzed, including 43 patients who received superficial temporal arterio-middle cerebral artery anastomosis (direct group) and 37 patients who received brain-dural arterio-artery vascularization (indirect group). The improvement of clinical symptoms, Modified Rankin Scale (mRS) Score, collateral vessels and CTP parameters were compared between the two groups.Results:The improvement of clinical symptoms in the direct group was better than that in the indirect group ( P<0.05), and the significant remission rate was significantly higher than that in the indirect group [86.0%(37/43) vs 59.5%(22/37), χ 2=7.262, P=0.007]. The postoperative mRS score in the direct group was significantly lower than that before surgery [0(0, 1) vs 1(1, 2), Z=5.550, P<0.001]. The score of mRS After surgery in the indirect group was significantly lower than that before surgery [0(0, 1) vs 1(1, 2), Z=4.281, P<0.001], but there was no statistically significant difference between the two groups ( P>0.05). There was no significant difference in digital subtraction angiography (DSA) collateral vessel formation between the two groups ( P>0.05). The CTP parameters of the two groups before and after surgery were consistent between observers and within observers [intraclass correlation coefficient (ICC) range 0.88-0.94]. In the operation area, the relative cerebral blood flow (rCBF) after surgery was significantly increased, and the relative time to peak (rTTP) and relative mean transit time (rMTT) were significantly decreased in both groups, with statistical significance ( P<0.05). In the ipsilateral basal ganglia and frontal lobe, rCBF in the direct group was significantly increased, rTTP and rMTT were significantly decreased, and the differences were statistically significant (all P<0.05), while there were no statistically significant differences in parameters in the indirect group (all P>0.05). The changes of rCBF, rTTP and rMTT in the operative area in the direct group were better than those in the indirect group, and the changes of rCBF, rTTP and rCBF in the basal ganglia and frontal lobe were better than those in the indirect group, with statistical significance (all P<0.05), while there were no statistically significant differences in the remaining parameters (all P>0.05). Conclusions:CT perfusion is of great value in evaluating the difference of clinical symptom improvement in the treatment of adult ischemic moyamoya disease with different vascular reconstruction methods.

ObjectiveTo explore the mechanism of Gancao Fuzitang （GCFZ）in inhibiting the bone destruction of collagen-induced arthritis （CIA） model in mice. MethodThirty male DBa/1J mice were randomly divided into normal group， CIA group， low-dose GCFZ group （GCFZ-L， 2.4 g·kg^-1）， high-dose GCFZ group （GCFZ-H， 4.8 g·kg^-1）， and methotrexate group （MTX， 1 mg·kg^-1）， with six mice in each group. The CIA model was induced by secondary immunization method. The arthritis index of mice in each group was observed and recorded， and the histopathological changes in ankle joint were observed by hematoxylin-eosin （HE） staining. The damage to ankle cartilage was detected by safranin O-fast green staining. Micro-CT scanning was used to detect the bone destruction of ankle joint， and the expression of nuclear factor-κB p65 （NF-κB p65）， p-NF-κB p65， inhibitory-κB kinase α/β （IKKα/β）， and p-IKKα/β was observed by immunohistochemical staining. ResultCompared with the normal group， the CIA group showed manifest joint swelling and increased arthritis index score （P<0.01）. Compared with the CIA group， the groups with drug intervention could inhibit joint swelling and reduce arthritis index score （P<0.05， P<0.01）. As revealed by HE staining and safranine O-green staining， compared with the CIA group， the groups with drug intervention could inhibit synovial invasion and reduce the destruction of articular cartilage. Micro-CT scanning analysis showed that compared with the CIA group， the GCFZ-H group and the MTX group showed reduced bone destruction scores （P<0.01）. The immunohistochemical results showed that compared with the normal group， the CIA group showed increased optical density values of NF-κB p65， p-NF-κB p65， IKKα/β， and p-IKKα/β（P<0.01）. Compared with the CIA group， the GCFZ-H group and the MTX group showed reduced optical density values of NF-κB p65， p-NF-κB p65， IKKα/β， and p-IKKα/β（P<0.05，P<0.01）. In the GCFZ-L group， only the NF-κB p65 optical density value decreased（P<0.01）. ConclusionGCFZ may inhibit bone destruction in CIA mice by regulating the NF-κB signaling pathway.

Objective:To understand the infectious status of Lyme disease among patients with arthritis symptoms in Hainan Province, and to provide a theoretical basis for prevention and control of Lyme disease.Methods:From 2013 to 2018, sampling surveys had been conducted in medical institutions in 8 cities in Hainan Province(Haikou, Sanya, Danzhou, Dongfang, Wenchang, Qionghai, Qiongzhong, Wuzhishan), 2 311 patients serum samples were collected with arthritis symptoms, and descriptive research were conducted base on the collected clinical data. The Indirect Fluorescent-Antibody Test (IFA) method was used for preliminary screening of Lyme disease antibody, the Western Blot (WB) method was used for IFA positive samples confirmation. Statistical analysis using χ2 test. Results:2 311 serum samples were tested by IFA, and 166 were positive with the positive rate of 7.18%. Further confirmed by WB method, 62 samples were positive, the positive rate of Lyme disease antibody was 2.68%(62/2 311). The positive rate of Lyme disease antibody among patients with arthritis in different regions of Hainan was statistically significant ( χ2 =40.636, P<0.001), and the positive rate in Qiongzhong city was the highest (8.81%, 14/159). Danzhou′s positive rate was the second highest, 5.62%(5/89). Dongfang city had the lowest positive rate (0.51%, 2/394). The positive rates of Lyme disease serum antibody in men and women were 2.79% (33/1 182) and 2.57% (29/1 129), respectively; the positive rates of antibodies between each age groups were in the range of 1.74% to 3.64%. The antibody positive rate of Lyme disease showed no significant difference between gender and age ( χ2 =0.110, P=0.740 ; χ2 =1.938, P=0.747). Conclusion:Patients with arthritis symptoms caused by Borrelia burgdorferi infection were found in 8 cities in Hainan province, but the Lyme disease antibody positive rate was different among cities, with Qiongzhong County being the highest.

Objective:To understand the infectious status of Lyme disease among patients with arthritis symptoms in Hainan Province, and to provide a theoretical basis for prevention and control of Lyme disease.Methods:From 2013 to 2018, sampling surveys had been conducted in medical institutions in 8 cities in Hainan Province(Haikou, Sanya, Danzhou, Dongfang, Wenchang, Qionghai, Qiongzhong, Wuzhishan), 2 311 patients serum samples were collected with arthritis symptoms, and descriptive research were conducted base on the collected clinical data. The Indirect Fluorescent-Antibody Test (IFA) method was used for preliminary screening of Lyme disease antibody, the Western Blot (WB) method was used for IFA positive samples confirmation. Statistical analysis using χ2 test. Results:2 311 serum samples were tested by IFA, and 166 were positive with the positive rate of 7.18%. Further confirmed by WB method, 62 samples were positive, the positive rate of Lyme disease antibody was 2.68%(62/2 311). The positive rate of Lyme disease antibody among patients with arthritis in different regions of Hainan was statistically significant ( χ2 =40.636, P<0.001), and the positive rate in Qiongzhong city was the highest (8.81%, 14/159). Danzhou′s positive rate was the second highest, 5.62%(5/89). Dongfang city had the lowest positive rate (0.51%, 2/394). The positive rates of Lyme disease serum antibody in men and women were 2.79% (33/1 182) and 2.57% (29/1 129), respectively; the positive rates of antibodies between each age groups were in the range of 1.74% to 3.64%. The antibody positive rate of Lyme disease showed no significant difference between gender and age ( χ2 =0.110, P=0.740 ; χ2 =1.938, P=0.747). Conclusion:Patients with arthritis symptoms caused by Borrelia burgdorferi infection were found in 8 cities in Hainan province, but the Lyme disease antibody positive rate was different among cities, with Qiongzhong County being the highest.

Objective:To investigate the clinical features and etiology of 176 children with liver dysfunction, and to provide reference for the diagnosis and treatment of children with liver dysfunction.Methods:From April 2017 to February 2019, 176 children with liver function abnormalities from 2 months to 13 years old who were admitted to Hangzhou Children's Hospital were selected inthe study.The pathogens of the children's secretions were detected by fluorescence quantitative method.The blood was tested for hepatitis B virus, hepatitis C antibody and hepatitis A antibody, and blood culture method was used to detect and identify bacteria, and blood genetic metabolism and coagulation function were also screened.According to the age of the children, they were divided into infant group, toddlergroup, preschool group and school age group.Results:Among the 176 children, the infants had the most abnormal liver function, 93 cases(52.84%), followed by 43 children (24.43%) in the toddler group.Causes of the disease: 138 cases (78.41%) of the original diseases, 8 cases (4.55%) of non-infectious diseases, 30 cases (17.04%) of the undetected pathogens.Among the 138 cases with liver function abnormality due to infectious diseases, 123 cases (89.13%) were infected with virus, 8 cases (5.80%) were infected with bacteria, 6 cases (4.35%) were infected with mycoplasma, and 1 case (0.72%) was infected with Toxoplasma gondii.Among the 123 cases of liver dysfunction caused by viral infection, cytomegalovirus was detected in 62 cases (50.41%), followed by EB virus in 38 cases (30.89%), rotavirus in 10 cases (8.13%), and EV71 virus in 5 cases (4.07%), 4 cases of common enterovirus (3.25%), 2 cases of respiratory syncytial virus (1.63%), 1 case of herpes simplex virus and Coxsackie A16 virus (0.81%). Pre-school and above were mainly infected with EB virus; the age>1 year-old liver function abnormality was 37.10% (23/62) due to cytomegalovirus, and the proportion of EB virus infection was 92.11% (35/38). Compared with 62.90% and 7.89% of age 2 months to 1 year, the difference was statistically significant (χ 2=29.27, P=0.00). Eightcases of liver infection caused by bacterial infection: 3 cases of Staphylococcus aureus, 2 cases of Streptococcus pneumoniae, 2 cases of Escherichia coli, and 1 case of Pseudomonas aeruginosa.There were 3 cases of genetic metabolic diseases, including 2 cases of hepatolenticular degeneration and 1 case of glycogen accumulation.Characteristics of liver function abnormalities in children: the main clinical manifestations of children were jaundice, splenomegaly and hepatomegaly, cough, diarrhea, etc.Outcome: 98 cases (55.68%) were healed, 60 cases (34.09%) were improved, and 17 cases (9.66%) were aggravated, 1 case of death (0.57%). Conclusion:The abnormal liver function of infants was mainly caused by virus infection, especially cytomegalovirus.Infants and young children have no obvious symptoms in the early stage of the disease, severe cases can be manifested as jaundice and hepatosplenomegaly, mainly mild, with a good prognosis.