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

Objective: To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients. Methods: From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed. Results: A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Conclusion The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.

Humans ; Asthma/drug therapy* ; Biological Therapy

OBJECTIVETo explore clinical features and mutation types in patients from Fujian area with glutaric academia type I(GA I).

METHODSSerum acylcarnitine and urine organic acid of 3 patients were determined with tandem mass spectrometry and gas chromatographic mass spectrometry. The patients also underwent magnetic resonance imaging analysis for the cranial region. Genomic DNA was extracted from peripheral blood samples, and the 12 exons and flanking regions of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing. One hundred healthy newborns were used as controls.

RESULTSMutations of the GCDH gene were identified in all of the 3 patients. Two patients have carried compound heterozygous mutations including c.1244-2A>C and c.1147C>T(p.R383C), c.406G>T(p.G136C) and c.1169G>A(p.G390E), respectively. One has carried homozygous c.1244-2A>C mutation. The same mutations were not detected among the 100 healthy newborns. Only one patient received early intervention and did not develop the disease. The other two had irreversible damagesto their intelligence.

CONCLUSIONc.1169G>A(p.G390E) is likely pathogenic mutations for GA I patients from Fujianarea. Early screening of neonatal metabolic diseases is crucial for such patients.

OBJECTIVETo evaluate the feasibility and efficacy of Zhu's trocar placement (ZTP) in laparoscopic appendectomy (LA) in the treatment of complicated appendicitis.

METHODSClinical data of 139 complicated appendicitis patients undergoing LA at the First Affiliated Hospital of Wenzhou Medical University from June 2013 to December 2017 were retrospectively analyzed. ZTP-LA group comprised 59 cases and its procedure was as follows: 10 mm umbilical trocar was used as lens port; 12 mm trocar at crossing point of umbilical hole horizontal line and right midclavicular line was used as main operating port; 5 mm trocar at the crossing point of horizontal line 0-3 cm below umbilicus and right anterior axillary line was used as assist operating port with the drainage function for Douglas fossa and right iliac fossa; The operator and the assistant stood on the right side and the left side of the patient respectively. Traditional three-port group comprised 80 cases (8 cases converted to laparotomy, 72 cases enrolled finally) and its procedure was as follows: 10 mm lens port below umbilicus; 10-12 mm main operating port at lateral border of left lower rectus abdominis; 5 mm assist operating port above pubis; The operator and the assistant stood on left side of the patient. The operative time, time to oral semi-fluid, postoperative hospital stay, cost during hospitalization, and postoperative morbidity of complication were compared between two groups.

RESULTSBaseline data such as gender, age, WBC count, percentage of leukocyte, pathological finding and type were not significantly different between two groups(all P>0.05). The conversion rate in ZTP-LA was significantly lower than that in traditional three-port group [0%(0/59) vs. 10.0%(8/80),χ²=4.552,P=0.033]. Compared with traditional three-port group, ZTP-LA group showed shorter operative time [(47.8±20.1) minutes vs. (66.0±27.3) minutes, t=4.383,P<0.001], shorter time to oral semi-fluid [(35.0±20.7) hours vs. (59.3±32.8) hours, t=5.158,P<0.001], shorter postoperative hospital stay [(4.1±1.6) days vs. (5.5±2.2) days, t=4.162, P<0.001], lower postoperative morbidity of complication [3.4% (2/59) vs. 18.1%(13/72), χ²=6.879, P=0.009], lower incidence of postoperative intra-abdominal abscess [0%(0/59) vs. 11.1%(8/72), χ²=5.179, P=0.023], lower incidence of paralytic ileus [1.7%(1/59) vs. 12.5%(9/72), χ²=3.946, P=0.047] and less cost during hospitalization[(13 585±2909) yuan vs.(16 861±5334) yuan, t=4.463, P<0.001].

CONCLUSIONZTP-LA is safe, feasible and effective with advantages of faster recovery and less cost in the treatment of complicated appendicitis.

Appendectomy ; methods ; Appendicitis ; surgery ; Humans ; Laparoscopy ; methods ; Length of Stay ; Postoperative Complications ; Retrospective Studies ; Surgical Instruments ; Treatment Outcome

Objective:In order to apply the index system for clinical evaluation of implementation effect in hospitals.Methods:A total of 862 patients with vaginal delivery from 9 hospitals were randomly divided into an clinical pathway group (n=496) and a control group (n=366).The patients in the control group received traditional treatment procedure while the patients in the clinical pathway group experienced procedure of the clinical treatment.The index system was used for clinical evaluation of implementation effect.Results:There were obvious advantages in 15 indicators in the clinical pathway group than those in the control group (P＜0.05).The comprehensive score of the clinical pathway group was higher than the control group of the corresponding grade and nature of the hospital.The comprehensive score for secondary hospitals (Ci=0.7967) were higher than that for the tertiary hospitals (Ci=0.2033).The comprehensive score for the general hospitals (Ci=0.8948) were higher than that for the specialized hospitals (Ci=0.1052).As for clinical implementation effect,the secondary hospitals were better than the tertiary hospital,and the general hospitals were better than the specialized hospitals.Conclusion:The index system for clinical evaluation could quantify the implementation effect,and compare the implementation effect in different hospitals,which provides reference for the management of clinical pathway.

Objective To assess the association of single nucleotide polymorphisms (SNPs)of biliverdin reductase A (BLVRA) with neonatal hyperbilirubinemia from Fujian area.Methods A total of 286 patients with neonatal hyperbilirubinemia and 250 healthy controls were enrolled.Genotypes of 5 SNPs within BLVRA gene including rs699512,rs1802846,rs7738,rs1637530 and rs2302032 were determined with matrix-assisted laser desorption ionization/time of flight mass spectrometer.The frequencies of genotype,allele,haplotype and their differentiations were analyzed.Results All 5 SNPs had conformed to Hardy-Weinberg equilibrium (all P ＞ 0.05).rs699512 and rs1637530 showed a significant difference between the 2 groups in both allelic and genotypic frequencies (all P ＜ 0.05),but no significant differences were found in the other SNPs(all P ＞ O.05).In recessive model,the frequency of rs699512 GG genotype of patients was significantly lower than that of the healthy control group(OR =0.494,95％ CI:0.276-0.886,P =0.018),while in dominant model,the frequencies of rs699512 GG + AG and rs1637530 TT + CT genotype of patients were significantly lower than that of the healthy control group(OR =0.678,0.627;95％ CI:0.482-0.954,0.444-0.885;P =0.026,0.008).Based on linkage disequilibrium analysis and haplotype construction,rs1637530,rs2302032,rs699512 and rs1802846 locus in the same area.Based on haplotype CGAT,TGGT,CTAT and CGGT had significant differences between the 2 groups (all P ＜ 0.05),and could reduce the risk of high blood bilirubin (OR =0.588,0.687,0.501;95％ CI:0.434-0.797,0.496-0.952,0.250-1.004).Conclusions rs699512 and rs1637530 may be associated with neonatal hyperbilirubinemia,A allele in rs699512 and C allele in rs1637530 may be associated with significantly increased risk of neonatal hyperbilirubinemia.

Objective To explore the time characteristics and neural mechanism of processing vertical spatial metaphor after the activation of moral disgust,by applying event-related potential technique (ERPs) and semantic priming paradigm.Methods Totally 22 healthy college or graduate students were randomly selected from a university in Henan Province.A dual word priming paradigm was used to present priming words (moral disgust words and non moral disgust words).Then the target words (neutral words above or on the bottom of the screen) were presented,and the subjects were asked to judge the font structure of the target words.Processing feature was explored by investigating the differences in EEG indexes of different combinations.Results The interaction between the starting stimulation of the correct rate and the target stimulation in the behavior data was significant (F=20.40,P＜0.01).In EEG data,compared with immoral aversion stimuli (P2:(0.81 ± 0.45) μV,N400:(-4.43 ± 0.58) μV),after the onset of moral abuses (P2:(-1.31 ± 0.40) μV,N400:(-5.04 ± 0.60) μV),the larger P2 (F =3.96,P＜ 0.05) and larger N400 (F =10.73,P＜0.01) amplitudes were induced in the related brain regions after the emergence of neutral words at the bottom of the screen.Conclusion The analysis of behavior and EEG data indicates that,compared with immoral disgust,moral abuses show a higher semantic connection with metaphorical moral,and metaphorical immoral shows lower semantic connection.The individual is more inclined to metaphorical morality to relieve and release the feeling of disgust and maintain a good self-moral image.

Objective To investigate the characteristics of point mutation,deletion or insertion mutations in Duchenne muscular dystrophy (DMD) gene.Methods Clinically confirmed 45 DMD patients without deletion/duplication mutation confirmed by MLPA in our hospital from January 2011 to November 2016 were chosen.Two generation sequencing technology was employed to detect DMD gene sequences.The features of tiny mutations were analyzed and summarized.Results In 45 patients without deletion/repeat mutation DMD,there were 66 mutations,including 24 missense mutations,20 nonsense mutations,12 splice site mutations,9 frameshift mutations and one synonymous mutation.There were 29 patients carrying one mutation,8 patents carrying 2 mutations,4 patients carrying 3 mutations,4 patients carrying 3 mutations,and one patient carrying 5 mutations.The exon 48 missense mutations were the most common,followed by exon 37 and exon 59;nonsense mutations,frameshift mutations,splice site mutations,and synonymous mutations had no obvious concentration distribution trend.Conclusion The exons 48,37 and 59 should be mainly considered during the drug research and development of tiny mutations,and readingthrough treatment of nonsense mutations is suitable for nonsense mutations.

Objective To analyze the clinical efficacy of the laparoscopic breast-conserving surgery combined with radiofrequency ablation to treat the early-stage breast cancer.Methods We collected 55 patients diagnosed early-stage breast cancer in retrospect,which started from January 2014 to December 2016.Twenty-seven of them were performed the laparoscopic breast-conserving surgery combined with radiofrequency ablation while others went through laparoscopic breast-conserving surgery without radiofrequency ablation.Meanwhile,we adopted the student t-test and the chi-square test to compare results of two groups.More specific,the main indexes of this study are including the post-operative local recurrence,the incidence of fat liquefaction or the incision-infection,operation time,post-operative hospital stay and the hospitalization expense.Results The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had low local-recurrence than the laparoscopic breastconserving surgery group (0 and 7.69％).Additionally,there were no statistical differences between two groups in the incidence of fat liquefaction.However,The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had more hospitalization expense than the laparoscopic breast-conserving surgery group [(4.1 ± 0.7) ten thousand yuan and (2.3 ± 0.6) ten thousand yuan,P ＜ 0.05].Conclusions Although the laparoscopic breast-conserving surgery combined with radiofrequency ablation group remarkably increased the hospitalization expense because of the utility of the radiofrequency ablation related apparatus,it may provide the probability of shaving more residual tumor cell and may low down the recurrence,especially not rising up the incidence of the post-operative fat liquefaction.Therefore,this surgery method might be one of the potential developments in the minimal-invasive of early stage breast cancer.