Purpose To explore the application and clini-cal significance of molecular detection in cell block specimens of lung adenocarcinoma.Methods A total of 200 cell block spec-imens of lung adenocarcinoma were collected.Among them 49 specimens underwent multi-gene panel detection(including EG-FR,EML4-ALK,ROS1,KRAS,HER2,BRAF,RET,MET,NRAS,and PIK3CA),while 151 specimens underwent EGFR single-gene detection.In addition,97 specimens were tested for EML4-ALK fusion gene alterations using the Ventana method,and the results were compared with that by PCR detection.The mutation characteristics were summarized,and the cytological features of the mutations and fusions were observed.Results The positive rate of driver gene mutations in 49 cases of multi-gene panel detection was 65.31％,which indicated no statisti-cally significant difference from that of 99 lung adenocarcinoma tissue specimens(P＞0.05).The positive rates of ALK,ROS1,and RET fusion mutations were 4.08％,4.08％,and 2.04％,respectively,and the positive rates of EGFR,KRAS,HER2,MET,and BRAF mutations were 38.78％,6.12％,4.08％,4.08％,and 2.04％,respectively.The mutation rate of EGFR in 151 cases of single-gene detection was 54.97％,with a mutation rate of 42.86％in males and 67.57％in fe-males,showing a statistically significant difference between gen-ders(P＜0.05).Exon 19 deletion mutation(19-Del)and exon 21 point mutation(21-L858R)in the EGFR gene took the high-est proportions,accounting for 54.22％and 37.35％,respec-tively,significantly higher than other mutation types(P＜0.001).The positive rate of EML4-ALK fusion gene immuno-histochemistry(IHC)in 97 cytological paraffin-embedded speci-mens was 15.46％,among which 6 cases with weak positivity(+)showed negative results in molecular detection,and 9 ca-ses with diffuse positivity(+++)showed positive results in molec-ular detection.The results of immunohistochemistry were highly consistent with molecular detection in cases with diffuse strong positivity(Kappa=1).It was found from the cytological mor-phology of cases with gene alterations that KARS mutation carri-ers were born with unique characteristics,with tumor cells scat-tered or arranged in small clusters and more cytoplasmic vacu-oles were commonly seen.Conclusion Molecular detection in cytological specimens of lung adenocarcinoma is feasible with higher sensitivity.Multi-gene panel detection is superior to sin-gle-gene detection.Immunohistochemistry can be used for screening EML4-ALK fusion gene,and lung adenocarcinoma with KRAS mutation that exhibits distinct cytological morpholo-gy.

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective:To analyze the nutritional status of elderly inpatients using Global Leadership Initiative on Malnutrition (GLIM) criteria.Methods:A total of 5 236 elderly patients (aged 65 years or older) who were hospitalized at the West China Hospital, Sichuan University from March 2021 to March 2022 were included. The nutritional status was analyzed using the GLIM diagnostic criteria for malnutrition.Results:The rate of patients at nutritional risk was 30.29%, and the incidence of malnutrition as per GLIM criteria was 15.64%. The levels of hemoglobin, albumin, triglycerides, and cholesterol, and body mass index of the malnutrition group were lower compared with the non-malnutrition group, and the differences were statistically significant ( P<0.05). The non-malnutrition group had significantly shorter hospital stay and lower hospitalization costs compared with the malnutrition group ( P<0.001). Conclusions:The GLIM criteria is suitable for evaluating the nutritional status in elderly inpatients. The incidence of malnutrition in elderly inpatients is relatively high, which deserves attention in clinical management.

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans ; U937 Cells ; RUNX1 Translocation Partner 1 Protein ; Leukemia/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Oncogene Proteins, Fusion/genetics* ; Leukemia, Myeloid, Acute/genetics*

Humans ; Castleman Disease/surgery* ; Kidney

Objective: To explore the impact of tennis on the visual health of primary school students, so as to provide a basis for myopia prevention. Methods: In September 2021, a total of 202 third grade students from Fengtai Affiliated School of Renmin University of China in Beijing were recruited, with 75 students in the intervention group and 127 students in the control group. In addition to attending the same cultural and physical education courses, the intervention group added a tennis course twice a week and tested their vision before the intervention (September 2021), middle (January 2022) and later (June 2022). Data collected at different time points in the two groups were analyzed by using independent sample t-test for comparison between blocks, and single factor repeated measurement ANOVA for analysis of time point factors. Results: After intervention, among male subjects, the average visual acuity of the left and right eyes in the intervention group were higher than that in the control group at the third visual acuity test (left eye:5.00±0.13,4.88±0.29, right eye:5.00±0.12,4.88±0.30, t =2.33, 2.36, P <0.05). Among female subjects, the second visual acuity test (left eye:5.03±0.17, 4.86±0.21, right eye:5.03±0.15, 4.85±0.23) and the third visual acuity test (left eye:4.97±0.13, 4.81±0.23, right eye:4.97±0.14, 4.82±0.24) showed that the average visual acuity of the left and right eyes in the intervention group were higher than that in the control group among females (second: t =3.84, 3.87, third: t =3.70, 3.46, P < 0.01 ). After intervention, the detection rate of visual impairment in both males and females control groups increased at three tests, with statistically significant differences ( χ 2=17.86, 34.77, P <0.01). In the first visual acuity test, there was no statistically significant difference in the detection rate of visual impairment between the control group and the intervention group for both males and females ( χ 2=0.01, 0.10, P >0.05). The third visual impairment detection rate of males in the intervention group was lower than that of the control group (20.00% vs 45.45%), while the second and third visual impairment detection rates of female students in the intervention group were lower than those of the control group (22.86% vs 54.00%; 28.57% vs 70.00%) ( χ 2=7.34, 8.24, 14.18, P < 0.01). Conclusions Tennis can alleviate and prevent the occurrence of myopia in primary school students to a certain extent. Sports such as tennis should be actively promoted to protect the visual health of primary school students.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Crizotinib/therapeutic use* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology* ; Gene Frequency

Purpose To explore the clinicopathological re-lationship between tumor budding and KRAS,NRAS,BRAF gene mutations and MSI status in colorectal adenocarcinoma and their clinical significance.Methods The clinical data of 237 cases of colorectal adenocarcinoma were collected to interpret tumor budding.RT-PCR was used to detect the gene mutations of KRAS,NRAS,BRAF in 229 cases and to analyze the corre-lation between tumor budding and gene mutations.MSI was de-tected by PCR and its relationship with tumor budding was ana-lyzed.Results Of the 237 patients,147 showed low-to medi-um-grade tumor budding and 90 showed high-grade tumor bud-ding.Tumor budding was associated with tumor size,vascular involvement,perineural invasion,tumor differentiation,lymph node metastasis,tumor nodule formation,tumor recurrence and TNM staging(P＜0.05),while it was not associated with age,sex and location.Single factor logistic regression analysis showed that tumor budding was associated with the risk of lymph node metastasis(P＜0.05),while multivariate logistic regres-sion analysis showed that tumor budding was an independent pre-dictor of lymph node metastasis in colorectal adenocarcinoma(P＜0.05).Of the 229 cases,the mutation rate of KRAS,NRAS and BRAF was 42.4％,2.6％and 3.1％,respectively.A-mong KRAS,NRAS and BRAF mutation cases,the proportion of high-grade tumor budding was 56.7％,33.3％and 14.3％,respectively.Tumor budding was associated with mutations in the Kras 12 and Kras 13 codons,as well as KRAS total muta-tions(P＜0.05).However,tumor budding had no relationship with NRAS and BRAF.In the high-grade budding tumors,KRAS mutations were mainly KRAS codons 12 and 13.Among the cases with KRAS mutation,the disease-free survival time and total survival time of the cases with high-grade tumor bud-ding were significantly shorter(P＜0.05).Of the 237 patients,the rate of MSI-H was 6.8％and only 2 out of 16 MSI-H pa-tients had high-grade tumor budding.There was a negative cor-relation between tumor budding and MSI status(r=-0.143,P＜0.05).Conclusion Tumor budding is related to the muta-tions in the Kras 12 and Kras 13 codons,as well as total KRAS mutations and MSI status.Tumor budding is also related to the prognosis of patients with colorectal adenocarcinoma,which can provide a reference for their outcome judgment.