Identification of Comprehensive Biomarkers in Patients With Mismatch Repair-Deficient Colon Adenocarcinoma Based on Parallel Multiomics.

Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer and other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, PCR-capillary electrophoresis is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline mismatch repair (MMR) mutations, the functional redundancy of the MMR system, and abnormal methylation of MutL Homolog 1 promoter. Therefore, this study aimed to develop new biomarkers for dMMR based on artificial intelligence (AI) and pathologic images, which may help to improve the detection accuracy. To screen for the differential expression genes (DEGs) in dMMR patients and validate their diagnostic and prognostic efficiency, we used the expression profile data from the Cancer Genome Atlas (TCGA). The results showed that the expression of Immunoglobulin Lambda Joining 3 in dMMR patients was significantly downregulated and negatively correlated with the prognosis. Meanwhile, our diagnostic models based on pathologic image features showed good performance with area under the curves (AUCs) of 0.73, 0.86, and 0.81 in the training, test, and external validation sets (Jiangsu Traditional Chinese Medicine Hospital cohort). Based on gene expression and pathologic characteristics, we developed an effective prognosis model for dMMR patients through multiple Cox regression analysis (with AUC values of 0.88, 0.89, and 0.88 at 1-, 3-, and 5-year intervals, respectively). In conclusion, our results showed that Immunoglobulin Lambda Joining 3 and nucleus shape-related parameters (such as nuclear texture, nuclear eccentricity, nuclear size, and nuclear pixel intensity) were independent diagnostic and prognostic factors, suggesting that they could be used as new biomarkers for dMMR patients.

ZNF185-derived peptide induces fertility suppression in mice.

Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in male reproduction. However, it is unclear whether ZNF185 may be a target candidate for contraceptive vaccines. In this study, antigenic peptides derived from ZNF185 were prepared, and their immune contraceptive effects were investigated using mice. Results from enzyme-linked immunosorbent assay (ELISAs) showed that peptide immunization induced an antibody titre increase that reached a peak in week 12. Peptide-3 and peptide-4 were then chosen for subsequent experiments. The results of the fertility assays showed that peptide immunization inhibited the mating and fertility rates of the mice, whereas there were no obvious changes in the number of pups per litter. Subsequently, epididymal sperm was analysed. The results demonstrated that the sperm count and sperm motility were significantly decreased in the peptide group, while the amount of abnormal sperm was significantly increased in the peptide-3 group. The male reproductive organs were also evaluated. There were no obvious differences in testis or epididymal weights, in the diameters of the seminiferous tubules, or in the thicknesses of the seminiferous epithelium between the peptide group and the phosphate buffer saline (PBS) group. In addition, histological analysis indicated that there were no obvious pathologic changes in testis and epididymal histology in the peptide group; however, the number of spermatozoa present in the epididymal lumen of the peptide group was significantly decreased when compared with the PBS group. Our study demonstrates for the first time that peptides derived from ZNF185 may induce fertility suppression in mice without damaging reproductive organs. These peptides have the potential to be used as a male contraceptive vaccine.

[Multicenter controlled study on transient asthma-stopping action of acupuncture at "Qingchuan point"].

OBJECTIVE: To test and verify the transient therapeutic effect of acupuncture at point "Qingchuan" on bronchial asthma. METHODS: Two hundred cases of bronchial asthma at acute attack stage were divided into a trial group of 100 cases treated with acupuncture at point "Qingchuan" and a control group of 100 cases treated with acupuncture at Dingchuan (EX-B1). RESULTS: The total effective rate was 92.60% and the effect occurred within 42-860 seconds after acupuncture in the trial group, and 81.0% and within 114-126 seconds in the control group, respectively, with very significant differences between the two groups (P < 0.01, P < 0.001). CONCLUSION: Acupuncture at point "Qingchuan" can significantly improve asthmatic state in the patient of bronchial asthma with action of rapidly stopping asthma.

Irritation of the human eye mucous membrane caused by airborne pollutants.

OBJECTIVES: The purpose of this study was to investigate the different irritative effects of carbon dioxide and n-butanol exposure on the ocular mucous membrane. MATERIAL AND METHODS: Provocation by the gases was at the same sensory level, which was 50% of maximum on a linear scale. The experiment was performed on nine healthy subjects with the aim of identifying the relationship between eye irritation and the human physiological response to this irritation. A goggle exposure system, invented at the Department of Occupational and Environmental Medicine, Aarhus University, was used for the experiment. The exposures lasted for 30 min each. RESULTS: There were no changes in tear film stability and conjunctival corrosion (lissamine staining) after carbon dioxide and n-butanol exposures leading to 50% sensory eye irritation. However, the study showed a delayed inflammatory response after carbon dioxide exposure when compared with clean air. The significant change was seen for tear fluid neutrophilic granulocytes 22 h after carbon dioxide (CO(2)) exposure only. CONCLUSIONS: It is concluded that the type of exposure made no difference to the elicited physiological responses and that tear film stability and epithelium damage were not affected by sensory irritation itself.