Objective Excision repair cross-complementing gene-1(ERCC1) are key regulatory enzymes whose expression patterns are associated with overall survival(OS) in several malignancies.Their expression patterns and prognostic value in resected gastric adenocarcinoma(GAC) are not known and need to investigate.Methods A total of 109 patients who underwent resection for GAC in Liu′an People′s Hospital from January 2010 to June 2013 had tissue available for analysis.The primary objective was to assess for the differential expression of ERCC1 using by immunohistochemistry.The secondary objective was to assess for the association between OS and the expression of ERCC1.Results The median follow-up was 21.2 months,and the median OS was 28.8 months.Resected GAC exhibited differential expression of ERCC1(high expression,n=25(23%)).ERCC1 expression was not associated with OS(18.9 months vs.27.7 months,P=0.72).In a subset analysis of patients who received chemotherapy(n=73),high ERCC1 expression was associated with decreased OS(16.7 months vs.53.8 months,P=0.03).After controlling for known adverse pathologic features,high ERCC1 expression persisted as a negative prognostic factor in multivariate Cox regression analysis(HR=2.22,95% CI1.05-4.98,P<0.05).Conversely,in patients who underwent resection only(n=35),high ERCC1 expression demonstrated a trend toward improved OS(40.4 months vs.12.7 months,P=0.10).A positive prognostic influence also was present on multivariate analysis(HR=0.20,95% CI0.05-0.84,P=0.03).Conclusion Resected GAC exhibited differential expression of ERCC1.Among all patients,ERCC1 expression levels were not associated with OS.High ERCC1 tumor expression is associated with decreased OS in the patients who received chemotherapy but is associated with increased OS in those who underwent surgery alone.ERCC1 expression have prognostic value in resected gastric cancer,and further investigation is needed.

A case of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) with ocular masses as the main manifestation was reported. The patient was a middle-aged female, the initial symptom was eye swelling, pulmonary nodules were found before eye surgery, and further examination revealed proteinuria, hematuria and renal insufficiency. Renal pathology showed ANCA-associated glomerulonephritis. The final diagnosis was eye, kidney and lung lesions caused by AAV. Treatment with glucocorticoids and cyclophosphamide resulted in improvement in eye, kidney, and pulmonary lesions. Atypical clinical manifestations of AAV may lead to delayed diagnosis, and attention should be paid to the exclusion of AAV for ocular masses of unknown cause.

Objective:To study the evolution of Traditional Chinese Medicine (TCM) syndromes of 171 cases of Kawasaki disease (KD) under the intervention of gamma globulin therapy based on factor analysis.Methods:A cross-sectional study. 171 cases of KD children hospitalized in the Department of Cardiology of Guangzhou Women's and Children's Medical Center from July 2019 to December 2020 were collected. All patients were treated with intravenous gamma globulin (2 g/kg) for 1 week. According to the results of the treatment with C-ball, 171 children with C-ball sensitive KD were selected to collect the four diagnostic data, and the representative syndromes of defensive level, qi level, yin level, and nutritive level were observed. Factor analysis was used to analyze the evolution of syndrome in 171 children with KD c-ball sensitivity.Results:The result of factor analysis showed that the KMO statistics of 171 children with c-ball sensitivity before treatment was 0.792, and Bartley test was significant ( P<0.01). 16 common factors were extracted, and 23 syndromes were screened, mainly including defensive level disorder, qi level disorder,nutritive level disorder,yin level disorder, heat stagnation and blood stasis syndrome. One week after treatment, the statistic of KMO test was 0.787, and Bartley test was significant ( P<0.01). 9 common factors were extracted, and 10 syndromes were screened, mainly including qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome. Conclusion:Before treatment, the TCM syndromes in KD C-cell sensitive children are mainly nutritive level disorder, defensive level disorder, qi level disorder yin level disorder, and heat stagnation and blood stasis syndrome; after treatment, the main TCM syndromes are mainly qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome.

Objective To explore the relationship between obesity and serum testosterone level among community adult males.Methods The stratified cluster sampling method was adopted to extract 1 166 male residents aged 20 years old and over in Zunyi City and conduct the questionnaire survey and physical examination.Fasting venous blood samples were collected for detecting the serum total testosterone(TT),sex hormone binding globulin(SHBG) and luteinizing hormone(LH).Then free testosterone index(cFT),free testosterone index(FTI) and testosterone secreting index(TSI) were calculated.Results The average levels of serum TT,SHBG,cFT,FTI,TSI and LH in 1 166 adult males were(16.83±4.90)nmol/L,(42.15 ± 20.21)nmol/L,(0.31 ±0.10)nmol/L,(0.46 ± 0.19) IU/L,(3.40 ± 2.04) IU/L and(6.77 ± 5.14) IU/L respectively;the Pearson correlation analysis showed that WHtR,BMI and WC were negatively correlated with TT,SHBG,TSI and LH,and were positively correlated with FTI,WHtR was negatively correlated with cFT,BMI and WC were negatively correlated with LH,the differences were statistically significant(P＜0.05).The multivariate linear regression analysis shown that WHtR was negatively correlated with TT,SHBG,TSI and LH;and was positively correlated with FTI,the differences were statistically significant(P＜0.01).Conclusion Adult male central obesity may be associated with the decrease of serum TT,SHBG,TSI and LH levels,and increase of FTI level.

Objective:To analyze the clinical features of patients with invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The clinical data of 12 patients diagnosed as IKLAS in Zhuzhou Central Hospital from January 2020 to January 2023 were retrospectively analyzed.Results:Among 12 patients there were 6 males and 6 females with an mean age of 65.3±12.2 years (49-90). Nine patients were complicated with type 2 diabetes. The main clinical manifestations were fever ( n=9), chill ( n=6), shiver ( n=4), nausea and vomiting ( n=2), upper abdominal pain ( n=2), fatigue and anepithymia ( n=2), cough and expectoration ( n=1), disturbance of consciousness ( n=1) and hemoptysis ( n=1). The leukocyte count was increased in 8 cases, lymphocyte count decreased in 10 cases, and platelets count decreased in 3 cases. C-reactive protein and procalcitonin levels were elevated, while serum albumin levels were lowered in all patients. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased in 7 cases each. Liver abscess was located in the right lobe in 8 cases, in the left lobe in 1 cases, and in both lobes in 3 cases. There were 7 patients with single abscess, and 5 patients with multiple abscesses. The etiology was confirmed by liver pus culture ( n=10) and blood culture ( n=5), respectively. The main sites of invasion were lung and blood stream ( n=10 and n=5, respectively). The majority of Klebsiella pneumoniae isolates were antibiotic sensitive strains and the overall drug resistance rate was relatively low. All patients were given antibiotics, and 10 of them also received liver abscess puncture drainage. After treatment, 11 patients were discharged, and 1 died of septic shock. Conclusions:Patients with IKLAS exhibit diverse clinical symptoms, most patients are complicated with diabetes, and the main sites of invasion are in the lungs and blood stream. Timely diagnosis, active screening of extrahepatic infection sites, effective drainage of abscess and appropriate antibiotic treatment can improve the survival of patients.

During the development of therapeutic microRNAs (miRNAs or miRs), it is essential to define their pharmacological actions. Rather, miRNA research and therapy mainly use miRNA mimics synthesized in vitro. After experimental screening of unique recombinant miRNAs produced in vivo, three lead antiproliferative miRNAs against human NSCLC cells, miR-22-3p, miR-9-5p, and miR-218-5p, were revealed to target folate metabolism by bioinformatic analyses. Recombinant miR-22-3p, miR-9-5p, and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells. Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs, inhibition of glucose uptake by miR-22-3p, and reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p in NSCLC cells. With greater activities to interrupt NSCLC cell respiration, glycolysis, and colony formation than miR-9-5p and -218-5p, recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity. These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine, which shall provide insight into developing antimetabolite RNA therapies.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors