Objective: To assess the association of genetic polymorphisms and circulating levels of chemokine monocyte chemoattractant protein-1 (MCP1) with risk of breast cancer. Methods: A total of 820 patients with pathologically confirmed breast cancer and 900 age-and area-of-residence-matched healthy controls who visited the hospital for routine health screening during the same period were included in this case-control study. Mendelian randomization analysis was performed using three widely followed functional single nucleotide polymorphisms (SNPs) of the MCP1 gene rs1024611, rs2857656 and rs4586 to construct instrumental variables.Results: MCP1 rs1024611 (OR=1.26, P=0.002), rs2857656 (OR=1.23, P=0.006) and rs4586 (OR=1.23, P=0.003) were significantly associated with increased risk of breast cancer. SNP rs1024611 (β=1.194, P<0.001), rs2857656 (β=1.221, P<0.001) and rs4586 (β=1.137, P<0.001) were positively correlated with higher circulating level of MCP1. The case-control study showed that an increase of 23.7 pg/ml of circulating levels of MCP1 was associated with a 0.25-fold increased risk of breast cancer. MR analysis confirmed that the genetic predicted circulating levels of MCP1 were associated with an increased risk of breast cancer, and the risk of breast cancer increased by 0.20 times with an increase of 23.7 pg/ml in MCP1. Conclusion: Genetic variants and circulating levels of MCP1 are significantly associated with the risk of breast cancer and can be used as a biomarker for early prediction of breast cancer.

To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL).

To investigate the association between WD40-encoding RNA antisense to p53 ( WRAP53 β), a telomerase new core subunit, and the clinical, genomic and immune infiltration characteristics of squamous cell carcinoma of the head and neck (HNSC), and to explore for potential joint targeted therapy of HNSC.

To investigate the regulatory role of extracellular vesicles (EVs) carrying ATP binding cassette transporter G2 (ABCG2) on the drug resistance of lung adenocarcinoma cells and the relevant molecular mechanisms.

To investigate the expression, biological function and potential mechanism of long intergenic non-coding RNA 01121 (LINC01121) in PCa.

Objective: To investigate the effects of long-chain noncoding RNA Linc00673 overexpression on proliferation and apoptosis of gastric cancer cells and its mechanisms. Methods: The recombinant lentivirus expressing plasmid pLVX-Linc00673 and the control empty plasmid pLVX-NC were packaged and amplified in 293T cells, and the recombinant lentivirus was transfected into gastric cancer cell line MGC-803 to establish a cell line stably overexpressing Linc00673. The expression of Linc00673 gene was detected by real-time fluorescence quantitative PCR. The growth and proliferation of cells were observed by MTT assay and clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. The expressions of cell cycle related regulatory genes were detected by qPCR. The expressions of key molecules in the PI3K/Akt signaling pathway and tumor proliferation related proteins were detected by Western blot. Results: The expressions of Linc00673 in gastric cancer cell line MGC-803, BGC-823 and AGS were significantly higher than that in normal gastric mucosa cell line GES-1 (P＜0.05). MGC-803 cell line with stable overexpression of LINC00673 was established, and the expression level of LincC00673 was 200 times higher than that of the control empty carrier group. Overexpression of Linc00673 promoted proliferation of MGC-803 cells (P＜0.05) and clone formation (P＜0.05), inhibited cell apoptosis and affected the G1→S phase progression of cell cycle (P＜0.01). Overexpression of Linc00673 could affect the expressions of cell cycle regulatory gene CCNG2, P19 and CDK1 in MGC-803. Western blot showed that Linc00673 overexpression not only promoted the expressions of the key molecule pAkt in PI3K / Akt signaling pathway and its downstream target NF-κ B and Bcl-2 protein, but also up regulated the expressions of tumor related factors β-catenin and EZH2 proteins. Conclusion: Overexpression of Linc00673 may promote proliferation and inhibit apoptosis of MGC-803 cells through PI3K/Akt signaling pathway.

To compare the effect of electroacupuncture (EA) on "Guanyuan" (CV4) or sensitization points in mice with polycystic ovary syndrome (PCOS), so as to explore its mechanisms underlying improvement of PCOS.

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

Objective To investigate whether tripartite motif containing 59 (TRIM59) influences the biological behavior of nasopharyngeal carcinoma cells by regulating the nuclear factor κB(NF-κB) signaling pathway. Methods TCGA database was used to predict the expression of TRIM59 in nasopharyngeal carcinoma and adjacent tissues. Reverse transcription PCR and Western blot were used to detect the relative expressions of TRIM59 mRNA and protein in nasopharyngeal carcinoma and paracancerous tissues. With human normal nasal mucosal epithelial cells (HNEpCs) as a control, reverse transcription PCR and Western blot analysis were used to detect the relative expression of TRIM59 mRNA and protein in HNE1 and CNE-2Z nasopharyngeal carcinoma cells. Small interference RNA technology was used to down-regulate the level of TRIM59 in HNE1 cells, while a control group, small interference RNA negative control (si-NC) group and TRIM59 small interference RNA (si-TRIM59) group were set up. MTT assay was used to detect the cell proliferation inhibition rate of each transfection group. TranswellTM chamber was used to detect cell invasion and migration ability of each transfection group. Western blot analysis was employed to detect NF-κB and phosphorylated NF-κB (p-NF-κB), vimentin, survivin protein expression. ELISA was adopted to detect interleukin 6 (IL-6), IL-8, tumor necrosis factor α (TNF-α) in the supernatant of cultured cells. Results The expression of TRIM59 increased abnormally in nasopharyngeal carcinoma tissues. Compared with HNEpC cells, the relative expression of TRIM59 in HNE1 significantly increased. After down-regulating the expression of TRIM59 in HNE1 cells, cell survival and cell invasion and migration were significantly inhibited. Down-regulating the expression of TRIM59 inhibited HNE1 cells p-NF-κB, vimentin, survivin protein expression and significantly reduced the levels of IL-6, IL-8, and TNF-α. Conclusion Down-regulation of TRIM59 blocks the NF-κB signaling pathway and tumor inflammation-related factors in HNE1 cells, thereby inhibiting cell invasion and migration.

Objective: To analyze the clinical characteristics and related genetic variation of juvenile myasthenia gravis (MG) patients. Methods: We collected the clinical data of adolescent MG patients who were treated in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from June 2019 to May 2020. After obtaining the patient's informed consent, the blood samples were collected. The Whole Exome Sequencing (WES) was performed on peripheral blood samples. And use biological information software and SPSS 22.0 for data processing and result analysis. Results: According to the inclusion and exclusion criteria, 54 patients with juvenile MG were included, 28 males and 26 females. And the average age of onset was (3.79±0.89) years. Among the enrolled patients, there were 52 (96.3%) patients with ocular MG, the MG-ADL scores of 54 patients were (3.44±0.44) points, and the titer of AChR antibody was (5.88±2.45) nmol/L. Two patients had thymic hyperplasia, and 5 patients had a family history of MG.A total of 169 variant genes were found in 54 patients, of which TTN gene variants had the largest number, with a total of 17 variants (31.5%). In the TTN gene variant group, 7(41.2%) patients had eye fixation symptoms, and 4 (10.8%) patients in the non-mutation group had eye fixation symptoms. And The difference between the two groups was statistically significant (P=0.016). In addition, the synaptic nucleus envelope protein-1 (SYNE1) and the ryanodine receptor-1 (RYR1) gene variations were also found in 7 cases (13.2%), and no clear relationship between these gene variations and clinical manifestations of MG was found. Conclusions: The incidence of juvenile MG was preschoolers with no gender difference, and ocular MG was more common. The proportion of TTN gene variation in adolescent MG was higher, suggesting that this gene may be a potential therapeutic target for juvenile MG patients.

Glioma is one of the most common central nervous system tumors in children.Increasing studies show that compared with adults, some gliomas in children have unique molecular genetic characteristics and completely different biological behaviors, although they are similar to adults in morphology and nomenclature. Therefore, pediatric glioma is by no means a "miniature version" of adults. In the 5th edition of WHO classification of central nervous system tumors published in the end of 2021, one of the most important revisions is the division of the classification into adult-type and pediatric-type diffuse gliomas, and the latter is further divided into pediatric-type diffuse low-grade gliomas and pediatric-type diffuse high-grade gliomas. In addition to histological morphology and clinical features, the basis of classification includes more molecular features. Therefore, in clinical practice, we need to pay more attention to the significance of molecular pathological diagnosis in the diagnosis and treatment of gliomas in children.

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations are the third most prevalent activating EGFR mutation in non-small cell lung cancer (NSCLC), accounting for 5%-12% of all EGFR mutations in NSCLC cases. Patients harboring EGFR exon 20 insertion mutations exhibit similar clinical characteristics except for worse prognosis as compared to those with 'classic' EGFR mutations. EGFR exon 20 insertion mutations are considered as a heterogeneous class of alterations that cause different conformational changes in EGFR. The majority of mutations (almost 90% of cases) is positioned in the loop that immediately follows the C-terminal of the C-helix, and the most widely reported subtype of insertion mutations is D770_N771>ASVDN(A767_V769dupASV) with frequency of 21%-28%. NSCLC patients with EGFR exon 20 insertion mutations show primary drug resistance to previously approved EGFR tyrosine kinase inhibitors and are generally insensitive to conventional chemotherapy and immunotherapy. The recently approved targeted drugs Amivantamab and Mobocertinib shift the treatment paradigm for NSCLC patients harboring EGFR exon 20 insertion mutations. There are also several new compounds targeting NSCLC EGFR exon 20 insertion mutations are in development. In this article, we provide a through overview on the treatment development in EGFR exon 20 insertion mutant NSCLC.
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m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer and regulates tumor immunity. Current studies mostly focus on the differential expression of some specific m6A effectors and infiltrating immune cell. m6A methylation modification is the result of mutual adjustment and balance between effectors, and changes in the expression of one or two effectors are far from enough to reflect the panorama of m6A methylation. The role of m6A in the immune microenvironment of lung adenocarcinoma (LUAD) is still poorly understood. The aim of this study is to investigate the effect of different m6A modification patterns in immune microenvironment of LUAD.

To investigate the association of molecular genetic polymorphism of KIR-HLA systems with acute lymphoblastic leukemia (ALL) and acute myelocytic leukemia (AML) in southern Chinese Han.

To analyze clinical phenotype and genetic variants in a Chinese pedigree of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.

Our previous studies have found that Stathmin, a microtubule depolymerizing protein, is a potential biomarker to guide locally advanced oral squamous cell carcinoma (OSCC) induction chemotherapy. This study further explored the regulatory effect of vincristine on Stathmin and its potention as an alternative chemotherapy drug.

The purpose of this study was to investigate the expression of HIST1H2BH in head and neck squamous cell carcinoma (HNSCC) and to analyze its clinical significance.

Objective To explore the effects of miR-335-5p derived from plasma exosomes on immune escape of triple-negative breast cancer (TNBC) via regulating ubiquitin-specific protease 22 (USP22). Methods The plasma of TNBC patients and healthy people was collected, then plasma exosomes were separated, and real time quantitative PCR was used to determine the relative expression of miR-335-5p in exosomes. The interaction between miR-335-5p and USP22 was verified by dual luciferase reporter assay. The expression of miR-335-5p and USP22 in exosomes and MDA-MB-436 cells was regulated. Exosomes or MDA-MB-436 cells were co-cultured with CD8+ T lymphocytes and subsequently divided into different groups.The apoptosis of cells in each group was detected by flow cytometry, and the levels of interferon γ (IFN-γ) and tumor necrosis factor α (TNF- α) in each group were detected by ELISA. The effects of USP22 on the stability of programmed death 1 ligand 1(PD-L1) was tested by Western blot analysis. The effects of miR-335-5p and PD-L1 on tumor growth was detected by tumor formation test in nude mice. Results The expression of miR-335-5p in TNBC exosomes was down-regulated. USP22 was confirmed as a target gene of miR-335-5p. In addition, USP22 could inhibit the ubiquitination of PD-L1 protein. Overexpression of miR-335-5p inhibited the immune escape of TNBC. Inhibition of miR-335-5p promoted the immune escape of TNBC, which could be partially saved by USP22 down-regulation. Knockdown of miR-335-5p promoted tumor growth in vivo, while tumor growth was inhibited by the addition of PD-L1 antibody. Conclusion Exosomal miR-335-5p promotes ubiquitination of PD-L1 by USP22 through down-regulating USP22, and inhibits TNBC immune escape mediated by PD-L1.

Objective To determine whether tumor cell membrane-encapsulated nanoparticles carrying programmed death 1 small interfering RNA (PD-1 siRNA) can target tumor tissues to inhibit the growth of oral squamous cell carcinoma, and whether it can trigger the anti-tumor immune response at the tumor site. Methods Membrane-siRNA nanoparticles(M-SNPs) was prepared by double emulsification solvent evaporation method and mechanical extrusion method. The morphology of M-SNPs was observed by transmission electron microscope. The particle size of M-SNPs was determined by differential scanning calorimetry. The uptake of M-SNPs by lymphocytes was observed by confocal microscope. The expression of PD-1after lymphocyte uptake of M-SNP was detected by qPCR. The tumor targeting capacity of M-SNPs was observed by in vivo imaging, and the tumor inhibitory activity of M-SNPs was evaluated in subcutaneous transplanted tumor model of SCC7 mouse squamous-cell carcinoma cells. The phenotype of tumor infiltrating T cells were detected by flow cytometry. Results Transmission electron microscope and differential scanning calorimetry showed that M-SNPs was successfully constructed. Confocal microscopy showed that lymphocytes could successfully ingest PD-1. Real-time quantitative PCR results showed that PD-1 expression was significantly down-regulated after M-SNPs uptake by lymphocytes. In vivo imaging results showed that M-SNPs could effectively target tumor tissue. SCC7 cell subcutaneously transplanted tumor model showed that M-SNPs could significantly inhibit tumor growth. The results of flow cytometry showed that the expression of antigen KI-67 (ki67) and IFN-γ in tumor infiltrating T cells significantly increased, while the expression of PD-1 and TIM-3 in immune checkpoints decreased significantly. Conclusion M-SNPs can mediate the specific targeted delivery of PD-1 siRNA to homologous tumor tissues, activate anti-tumor immune response and inhibit tumor growth, which may be a potential therapeutic strategy for oral cancer.

Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC.