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*

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective:To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods:This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children′s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results:Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions:Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Objective:To investigate the effect of homogeneous management combined with staged teaching on physicians receiving standardized training of hepatobiliary surgery.Methods:A total of 46 physicians who received standardized training in Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, from January to March 2020 were selected as control group and were given conventional teaching, and 50 physicians who received standardized training from April to June 2020 were selected as observation group and were given homogeneous management combined with staged teaching. The two groups were compared in terms of professional level, clinical ability, and the degree of satisfaction with teaching before and after teaching. SPSS 24.0 was used to perform the independent samples t-test, the paired t-test, the chi-square test, and the rank sum test. Results:After teaching, both groups had significant increases in the scores of theoretical examination and operation skill examination, and compared with the control group, the observation group had significantly higher scores of theoretical examination (94.57±3.28 vs. 90.32±2.12) and operation skill examination (94.37±4.18 vs. 91.25±3.46). After teaching, both groups had significant increases in the scores of clinical consultation, physical examination, humanistic concern, clinical diagnosis, communication ability, organizational ability, and overall evaluation, and the observation group had significantly higher scores of the above seven aspects than the control group (6.98±0.94/6.45±0.14/6.95±0.88/6.65±0.93/6.53±0.26/6.84±0.92/6.58±0.35 vs. 6.13±0.31/6.21±0.76/6.21±0.42/6.18±0.35/6.32±0.61/6.33±0.24/6.25±0.71). The observation group had a significantly higher overall satisfaction rate than the control group [94.00% (47/50) vs. 78.26% (36/46)].Conclusion:In the standardized training and teaching of hepatobiliary surgery, homogeneous management combined with staged teaching can improve the professional level and clinical ability of physicians and enhance the degree of satisfaction with teaching.

Objective:To analyze the status quo and influencing factors of accidental prolapse of peripherally inserted central catheter (PICC) in children, so as to provide references for formulating preventive measures.Methods:Using the convenient sampling method, a total of 1 268 pediatric patients who underwent catheterization at Intravenous Catheter Nursing Studio of Beijing Children's Hospital, Capital Medical University from January to December 2021 were selected as the research objects to analyze the incidence of PICC accidental prolapse. Logistic regression was used to analyze the influencing factors of PICC accidental prolapse.Results:Of the 1 268 children included in this study, 29 were excluded from follow-up and 1 239 children were eventually included. A total of 1 339 PICCs were implanted in 1 239 children, and the incidence of PICC accidental prolapse was 5.60% (75/1 339). Logistic regression analysis showed that whether the children had skin rash, time, location and catheter indentation time were the influencing factors for the occurrence of PICC accidental prolapse ( P<0.05) . Conclusions:The incidence of children's PICC accidental prolapse is at a high level, which is affected by many factors. Nursing staff should formulate effective preventive measures according to the influencing factors of PICC accidental prolapse, reduce the occurrence of children's accidental catheterization and extend the retention time of PICC.

Objective:To investigate the effects of curcumin on proliferation, cell cycle, and apoptosis of human thyroid cancer TPC-1 cells.Methods:Logarithmic growth phase TPC-1 cells were treated with 0.0, 7.5, 15.0 and 22.5 μmol/L curcumin for 48 h. Cell proliferation levels were determined using the methylthiazolyl tetrazolium (MTT) assay. Cell cycle and apoptosis levels were measured using flow cytometry. Western blot method was used to determine the expression levels of B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax).Results:The inhibition rates of cell proliferation in 7.5, 15.0 and 22.5 μmol/L curcumin groups were higher than that of 0.0 μmol/L curcumin group ( P < 0.05); the proportion of G0/G1 phase was higher than that of 0.0 μmol/L curcumin group, but the proportions of G2/M and S phase were lower than those of 0.0 μmol/L curcumin group ( P < 0.05); the cell apoptosis rate was higher than that of 0.0 μmol/L curcumin group [(14.13 ± 0.57)%, (25.27 ± 0.62)%, (36.01 ± 0.84)% vs (8.48 ± 0.43)%, P < 0.05]; the protein expression of Bcl-2 was lower than that of 0.0 μmol/L curcumin group, and protein expression of Bax was higher than that of 0.0 μmol/L curcumin group ( P < 0.05). Conclusion:Curcumin can inhibit the proliferation of TPC-1 cells, block the cell cycle in G0/G1 phase, and promote cell apoptosis by downregulating Bcl-2 expression and upregulating Bax expression.

Objective:To investigate the clinical efficacy of cyclophosphamide combined with leflunomide in the treatment of lupus nephritis.Methods:The clinical data of 90 patients with lupus nephritis who received treatment in The Second People's Hospital of Liaocheng from January 2019 to June 2020 were retrospectively analyzed. These patients were divided into two groups according to different treatment methods. The single drug group ( n = 45) was treated with cyclophosphamide alone, and the combined drug group ( n = 45) was treated with cyclophosphamide combined with leflunomide. All patients were treated for 6 months. Total response rate, inflammatory factor level, immune function, renal function, and adverse reactions were compared between the two groups. Results:Total response rate in the combined drug group was 95.56% (43/45), which was significantly higher than 82.22% (37/45) in the single drug group ( χ2 = 4.05, P < 0.05). After treatment, interleukin-6, C-reactive protein, and rheumatoid factor in the combined drug group were (45.21 ± 5.07) ng/L, (3.13 ± 1.01) mg/L, (43.37 ± 18.20) IU/mL, respectively, which were significantly lower than (60.20 ± 6.13) ng/L, (6.23 ± 1.31) mg/L, (73.19 ± 19.17) IU/mL in the single drug group ( t = 12.64, 12.57, 7.56, all P < 0.001). Immunoglobulin A and immunoglobulin G levels in the combined drug group were significantly lower than those in the single drug group ( t = 13.05, 13.40, both P < 0.001), but immunoglobulin M level in the combined drug group was significantly higher than that in the single drug group ( t = 13.51, P < 0.001). Serum creatinine and 24-hour urine protein levels in the combined drug group were (78.23 ± 19.13) μmol/L and (1.15 ± 0.33) g/24 hours, respectively, which were significantly lower than (92.19 ± 20.19) μmol/L and (3.15 ± 0.81) g/24 hours in the single drug group ( t = 3.36, 15.33, both P < 0.001). The incidence of adverse reactions in the combined drug group was 6.67% (3/45), which was significantly lower than 22.22% (10/45) in the single drug group ( χ2 = 4.40, P < 0.05). Conclusion:Cyclophosphamide combined with leflunomide is effective against lupus nephritis. The combined therapy can regulate the inflammatory reaction, improve the immune function, promote the recovery of renal function, and be safe.

Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer.
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Humans ; Lung Neoplasms ; Carcinogenesis ; Inflammation

Objective:To investigate the effect of hemodiafiltration combined with Jinshuibao tablet on serum inflammatory factors and oxidative stress indices in patients with diabetic nephropathy. Methods:A total of 86 patients with diabetic nephropathy who received treatment in The Second People's Hospital of Liaocheng from April 2019 to April 2020 were included in this study. They were randomly assigned to receive either hemodiafiltration (control group, n = 42) or hemodiafiltration combined with Jinshuibao tablet (observation group, n = 44). Microinflammatory state, oxidative stress index level, renal function and nutritional status were compared between the two groups. Results:Before treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels in the control group were (30.13 ± 3.25) ng/L, (9.43 ± 2.57) mg/L, (46.69 ± 3.54) ng/L respectively, and they were (30.16 ± 3.34) ng/L, (9.48 ± 2.65) mg/L, (46.73 ± 3.38) ng/L respectively in the observation group. There were no significant differences in these indices between the two groups (all P > 0.05). After treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels in the control group were (16.69 ± 2.73) ng/L, (8.12 ± 2.21) mg/L, (35.63 ± 2.75) ng/L, respectively, and they were (12.34 ± 2.52) ng/L, (6.47 ± 1.53) mg/L, (26.65 ± 2.13) ng/L, respectively in the observation group. After treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels in both groups were significantly lower than those before treatment (control group: t = 20.52, 2.50, 15.99; observation group: t = 27.60, 6.16, 32.57, all P < 0.05). After treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels were significantly lower than those in the control group ( t = 7.68, 4.04, 16.97, all P < 0.05). Before treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in the control group were (5.63 ± 1.36) nmol/L, (63.38 ± 7.56) mU/L, and (195.96 ± 26.36) IU/L, respectively, while those in the observation group were (5.68 ± 1.25) nmol/L, (63.25 ± 7.38) mU/L, and (195.83 ± 26.27) IU/L, respectively. There were no significant differences in these indices between the two groups (all P > 0.05). After treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in the control group were (4.83 ± 1.13) nmol/L, (83.46 ± 5.75) mU/L and (236.69 ± 18.75) IU/L respectively, while those in the observation group were (4.24 ± 0.86) nmol/L, (88.75 ± 5.47) mU/L and (258.76 ± 15.47) IU/L, respectively. After treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in each group were superior to those before treatment (control group: t = 2.93, 13.70, 8.16, P = 0.002, < 0.001, < 0.001; observation group: t = 6.15, 17.99, 13.37, all P < 0.001). After treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in the observation group were superior to those in the control group ( t = 2.73, 4.37, 5.96, P = 0.004, < 0.001, < 0.001). After treatment, blood urea nitrogen, serum creatinine and 24-hour urine protein in the observation group were significantly lower than those in the control group ( t = 7.85, 8.71, 2.06, P < 0.001, < 0.001, 0.021), and creatinine clearance rate in the observation group was significantly higher than that in the control group ( t = 3.01, P = 0.002). Total protein, prealbumin and albumin levels in the observation group were significantly higher than those in the control group ( t = 9.47, 12.13, 6.18, all P < 0.001). Conclusion:Hemodiafiltration combined with Jinshuibao tablet for the treatment of diabetic nephropathy has a positive effect on microinflammatory state and oxidative stress index level and improves patient's renal function and nutritional status.

Objective:To investigate the efficacy of tripterygium glycoside tablets combined with irbesartan for chronic nephritis and its effect on 24-hour urine protein and inflammatory factor levels.Methods:Ninety patients with chronic nephritis who received treatment at The Second People's Hospital of Liaocheng from April 2018 to January 2020 were included in this study. They were randomly divided into an observation group and a control group, with 45 patients in each group. The control group was treated with irbesartan. The observation group was treated with tripterygium glycoside tablets combined with irbesartan. All patients were treated for 3 successive months. Clinical efficacy and adverse reactions were compared between the two groups. Changes in 24-hour urine protein level, symptom score, and inflammatory factor levels after treatment relative to those before treatment were compared between the two groups.Results:Response rate in the observation group was significantly higher than that in the control group [95.6% (43/45) vs. 80.0% (36/45), χ2 = 5.07, P = 0.024). Before treatment, there were no significant differences in 24-hour urine protein level, symptom score, and inflammatory factor level between the two groups (all P > 0.05). After treatment, the 24-hour urine protein level in the observation group was significantly lower than that in the control group [(1.42±0.01) g/24 hours vs. (1.95 ± 0.05) g/24 hours, t = 69.72, P = 0.012). The symptom score in the observation group was significantly lower than that in the control group [(0.78 ± 0.01) points vs. (1.33 ± 0.12) points, t = 30.64, P = 0.001]. Serum levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α in the observation group were significantly lower than those in the control group ( t = 15.70, P = 0.006; t = 96.55, P = 0.003; t = 43.41, P = 0.002). There was no significant difference in the incidence of adverse reactions between the two groups ( P = 0.694). Conclusion:Tripterygium glycoside tablets combined with irbesartan is highly effective on chronic nephritis. The combined therapy can remarkably decrease 24-hour urine protein levels, reduce symptom scores, and decrease inflammatory factor levels.