Objective:To analyze the predictive value of tumor-infiltrating lymphocyte (TIL) fraction in patients with breast cancer treat-ed with neoadjuvant chemotherapy. Methods: Clinicopathological data of 156 female patients with breast cancer diagnosed using core needle biopsy and treated with neoadjuvant chemotherapy and surgery between November 2015 and April 2017 in Tianjin Medi-cal Uninvertity Cancer Institute and Hospital were retrospectively analyzed. Patients were assigned into 3 groups based on the TIL frac-tim, namely high, intermediate and low TIL fractin gronp. The response to neoadjuvant chemotherapy was evaluated using the histo-pathological criteria for assessment of therapeutic response in breast cancer. The relation between TIL fraction and response to neoad-juvant chemotherapy was then analyzed. Results:Neoadjuvant chemotherapy was effective in 78.2%(122/156) of the patients. Pa-tients harboring tumors with a higher TIL fraction were more likely to achieve a better response to neoadjuvant chemotherapy than those harboring tumors with a lower TIL fraction (P<0.01). Patients harboring hormonal receptor (HR)-negative tumors generally exhib-ited a higher TIL fraction than those harboring HR-positive tumors (P<0.01). The TIL fraction, but not HR status, human epidermal growth factor receptor 2 (HER-2) status, or Ki-67 index, correlated with response to neoadjuvant chemotherapy. Conclusion:TIL frac-tion is an independent predictive factor of response to neoadjuvant chemotherapy in patients with breast cancer. Patients with breast cancer exhibiting higher TIL fraction achieve better response to neoadjuvant chemotherapy than those exhibiting lower TIL fraction.

The industry of germ-free animals has been a hot spot in research along with the rapid development of studies on the relationship between microbiota and host diseases. Because it is pathogen?free, and the high degree of simi?larity in anatomy, physiology, pathogenesis to humans, germ?free pig is considered a clinical relevant model to be widely used in life science research. Based on the current state of research of germ?free pig cultivation at home and abroad and the experimental studies carried out in our laboratory as well, this article gives a simple discussion on germ?free technique of domestic pigs.

OBJECTIVETo investigate the effect of anti-EGFR monoclonal antibody on the chemosensitivity of human colon cancer cells and explore the possible molecular mechanism.

METHODSThe inhibitory effect of irinotecan (CPT-11), oxaliplatin (L-OHP) and fluorouracil (5-Fu), used alone or in combination with anti-EGFR monoclonal antibody, on the proliferation of LoVo cells in vitro was assessed by MTT assay. The expressions of PI3K and Akt protein in the treated cells were examined by Western blotting, and their mRNA expressions were detected by RT-PCR.

RESULTSBoth h-R3 and C-225 treatments significantly increased the chemosensitivity of LoVo cells to irinotecan and oxaliplatin. 5-Fu and h-R3 coadministered showed a synergistic effect on the cells, but 5-Fu and C-225 had an antagonistic action. Treatment with C-225 or h-R3 resulted in lowered expressions of PI3K and Akt in LoVo cells.

CONCLUSIONAnti-EGFR monoclonal antibody can increase the chemosensitivity of human colon cancer cells to most chemotherapeutic drugs, and such effect might be attributed to the blocking of PI3K/Akt signaling pathway by these antibodies.

Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Cetuximab ; Colonic Neoplasms ; drug therapy ; metabolism ; Humans ; Oncogene Protein v-akt ; metabolism ; Receptor, Epidermal Growth Factor ; immunology ; Signal Transduction

OBJECTIVETo investigate the clinical significance of vascular endothelial growth factor (VEGF) levels in serums of colorectal cancer patients at stage IV.

METHODSUsing enzyme linked immunosorbent assay (ELISA) to detect the VEGF levels in serums of 45 colorectal cancer patients at stage IV, and 20 healthy served as normal control.

RESULTSThe mean concentration of VEGF in 45 colorectal cancer patients at the 7 day after operation were significantly lower than that before operation (P<0.01). The mean concentration of VEGF in the patients who benefit from bevacizumab showed no statistical difference from the levels of who did not benefit (P=0.554).

CONCLUSIONThe VEGF levels in colorectal patients at stage IV are lowed as the load of tumor decrease. The circulating levels of VEGF seem not predict the response to bevacizumab in colorectal cancer patients at stage IV.

Adolescent ; Adult ; Aged ; Antibodies, Monoclonal ; administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bevacizumab ; Colorectal Neoplasms ; blood ; drug therapy ; pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Vascular Endothelial Growth Factor A ; blood ; Young Adult

Objective:To observe the effect of combining biofeedback therapy (BFT) based on virtual reality technology with repeated transcranial magnetic stimulation (rTMS) on dysphagia among stroke survivors.Methods:Eighty patients were randomly divided into a control group, an rTMS group, a BFT group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the rTMS and BFT groups were given those treatments, while the combined treatment group was given both for 4 weeks. Swallowing function was evaluated before and after the treatment using the standardized swallowing assessment (SSA) and the functional oral intake scale (FOIS). Videofluoroscopy was used to quantify the subjects′ oral and pharyngeal phases and their aspiration status.Results:Significant improvement was observed in the average FOIS and SSA scores, as well as in the average oral and pharyngeal phases and in aspiration. The combined treatment group′s results were significantly better in all those aspects than those of the other 3 groups.Conclusion:The combined application of biofeedback therapy based on virtual reality technology and repeated transcranial magnetic stimulation can improve the swallowing function of stroke survivors with dysphagia. It is worthy of clinical promotion.

Objective To determine the effect of miR-196 on sensitivity of endocrine therapy for breast cancer and to explore its possible molecular mechanism.Methods The expression of miR-196 was detected by real-time quantitative PCR (RT-qPCR) in MCF7 (ER+) and BT549 (ER-).The sensitivity of tamoxifen on MCF7 cells was evaluated by MTT and colony formation.Dual-luciferase,RT-qPCR and western blot assays were used to determine the regulation of miR-196 on p27.Results The expression of miR-196 was up-regulated in BT549 compared to that in MCF7 cells.The cell viability and colony formation were increased in miR-196-overexpressed MCF7 cells compared to those in the control cells after treatment with tamoxifen.The luciferase activity and expression of p27 were decreased in miR-196-overexpressed MCF7 cells compared to those in the control cells.Overexpression of p27 eliminated the effect of miR-196-induced endocrine therapy resistance in MCF7 cell.Conclusion miR-196 promotes breast cancer endocrine resistance by targeting p27.

Objective: To evaluate the roles of G Protein-Coupled Receptor 68 (GPR68) and tumor infiltrating lymphocytes (TIL) in TPF-(paclitaxel, cisplatin and 5-fluorouracil) induced chemotherapy for middle-advanced hypopharyngeal squamous cell carcinomas. Methods: A total of 31 patients with middle-advanced hypopharyngeal squamous cell carcinoma before TPF-inducted chemotherapy were enrolled from September 2012 to November 2017 in Beijing Tongren Hospital, Capital Medical University, including 28 males and 3 females, aged 43 to 71 years old. The expression of GPR68 and tumor infiltrating CD4⁺and CD8⁺T cells before chemotherapy was detected by immunohistochemical staining, and the relationships between GPR68 expression and clinical features, chemotherapy efficacy and overall survival (OS) were analyzed using t-test. Results: After 3 cycles of chemotherapy, there were 4, 14, 10 and 3 patients respectively with complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The positive rates of GPR68 and CD8 were 25% and 40% respectively in the effective group (CR+PR), while 50% and 15% in the ineffective group (SD+PD), with statistically significant differences between two groups (t=5.17 and 12.86,P<0.001). Linear regression analysis showed that GPR68 was negatively correlated with CD8⁺T cells (r=-0.64,P<0.001). There was no significant correlation between the CD4 expression and TPF efficacy (P>0.05). The mean OS was 12.5 months in patients with high-expressed GPR68 and 25.0 months in patients with low-expressed GPR68, with a statistically significant difference (P=0.005). And mean OS was 25.0 months in patients with high-expressed CD8 and 14.5 months in low-expressed CD8, with a statistically significant difference (HR=2.58, P=0.019). Cox regression analysis showed that GPR68 and CD8⁺T cells were significant prognostic factors (OR(95%CI)=3.27(2.46-5.97) and 1.53(0.78-1.82), all P<0.05), while CD4 had no significant effect on prognosis (P>0.05). Conclusion: GPR68 and CD8⁺T cells are expected to be biomarkers for evaluating the efficacy and prognosis of TPF-induced chemotherapy in patients with middle-advanced hypopharyngeal squamous cell carcinoma.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cisplatin ; Female ; Fluorouracil ; Head and Neck Neoplasms/drug therapy* ; Humans ; Induction Chemotherapy ; Lymphocytes, Tumor-Infiltrating ; Male ; Middle Aged ; Prognosis ; Receptors, G-Protein-Coupled ; Squamous Cell Carcinoma of Head and Neck

OBJECTIVE: To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment. METHODS: The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias. CONCLUSION Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.
Child ; Humans ; Acupuncture Therapy/methods* ; Autistic Disorder ; Moxibustion/methods* ; Publication Bias ; Research Design ; Systematic Reviews as Topic ; Meta-Analysis as Topic

OBJECTIVETo investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 (MAGI3) in glioma cell proliferation.

METHODSThe expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis (GSEA).

RESULTSExpression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples.

CONCLUSIONThe loss of MAGI3 expression in glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

Animals ; Brain Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; genetics ; Down-Regulation ; Glioma ; genetics ; metabolism ; pathology ; Humans ; Membrane Proteins ; genetics ; metabolism ; Mice, Nude ; PTEN Phosphohydrolase ; genetics ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction ; Transfection ; Up-Regulation ; Xenograft Model Antitumor Assays

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.
Betacoronavirus ; COVID-19 ; Computational Biology ; Coronavirus Infections/complications* ; Gene Expression Profiling ; Gene Ontology ; Heart Failure/virology* ; Humans ; Pandemics ; Pneumonia, Viral/complications* ; SARS-CoV-2