Background The diagnosis of cow’s milk protein allergy(CMPA) may be easily misdiagnosed due to its lack of specific symptoms. Thus, experts have proposed the use of Cow’s milk-related symptom scores (CoMiSS) to predict CMPA. There has been no relevant report on the clinical application value of CoMiSS in Chinese children. This study aimed to evaluate the effect of CoMiSS in early identification of CMPA in Chinese infants. Methods We calculated CoMiSS for 38 infants with suspected CMPA diagnosed in the pediatric gastroenterologic clinic in our hospital. After 4 weeks of dietary elimination and symptomatic improvement, these infants returned to our hospital to undergo oral food challenge (OFC). The ROC curve was used to determine the sensitivity and specificity of CoMiSS and evaluate the effect of CoMiSS in early identification of CMPA in Chinese infants. We didn’t determine the CoMiSS of presumed healthy infants as control group. Results Of 38 infants who underwent OFC testing, the average CoMiSS of infants with positive OFC testing was 7.4 ± 2.3, while the average CoMiSS of infants with negative OFC testing was 4.1 ± 1.6, and there was a significant difference between two groups( F = 2.13, P< 0.05). The area under the ROC curve (AUC) of CoMiSS was 0.89, and the best diagnostic cut-off point was 5.5. The sensitivity of CoMiSS was 87.5%, while the specificity of CoMiSS was 78.6%. Conclusion CoMiSS is a simple and operable method to screen for CMPA, though there may be a risk of under-diagnosis when CoMiSS≥12 is used as the criterion for early identification of CMPA in Chinese infants. More multi-center studies are needed to evaluate whether the factors such as bloody stool should be included in CoMiSS or CoMiSS≥6 can be used as the criterion for early identification of CMPA in Chinese infants.

Idiopathic central precocious puberty (ICPP) is a relatively common condition in preadolescent girls, and its pathogenesis remains to be uncovered. A variety of studies have highlighted the association of gut microbiota (GM) with endocrine diseases, such as obesity, which is commonly associated with ICPP. However, the relationship between GM and ICPP remains unexplored. Feces samples were collected from 25 girls with ICPP (ICPP group) and 23 healthy girls (Control group). We applied 16S rDNA sequencing to compare the GM between two groups. The ICPP group had higher GM diversity and was enriched for several GM species, including Ruminococcus gnavus, Ruminococcus callidus, Ruminococcus bromii, Roseburia inulinivorans, Coprococcus eutactus, Clostridium leptum, and Clostridium lactatifermentans, which are known to be associated with obesity and are related to the production of short-chain fatty acids. Additionally, 36 candidate GM biomarkers for patients with ICPP screening were identified with high accuracy (AUC = 0.95, 95% CI 0.88 to 1). We observed that the GM of the ICPP group was enriched for the microbial functions of cell motility, signal transduction, and environmental adaptation. Positive correlations were also detected between Fusobacterium and follicle-stimulating hormone, and Gemmiger and luteinizing hormone. This study documents relationships between GM and ICPP, and the implication of these findings remains to be determined.

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Neutrophils are important innate immune cells involved in microbial clearance at the sites of infection. However, their role in cancer development is unclear. We hypothesized that neutrophils mediate antitumor effects in early tumorigenesis. To test this, we first studied the cytotoxic effects of neutrophils in vitro. Neutrophils were cytotoxic against tumor cells, with neutrophils isolated from tumor-bearing mice trending to have increased cytotoxic activities. We then injected an ELR+ CXC chemokine-producing tumor cell line into C57BL/6 and Cxcr2−/− mice, the latter lacking the receptors for neutrophil chemokines. We observed increased tumor growth in Cxcr2−/− mice. As expected, tumors from Cxcr2−/− mice contained fewer neutrophils. Surprisingly, these tumors also contained fewer CD8+ T cells, but more IL-17-producing cells. Replenishment of functional neutrophils was correlated with decreased IL-17-producing cells, increased CD8+ T cells, and decreased tumor size in Cxcr2−/− mice, while depletion of neutrophils in C57BL/6 mice showed the opposite effects. Results from a non-ELR+ CXC chemokine producing tumor further supported that functional neutrophils indirectly mediate tumor control by suppressing IL-17A production. We further studied the correlation of IL-17A and CD8+ T cells in vitro. IL-17A suppressed proliferation and IFNγ production of CD8+ T cells, while CD11b+Ly6G+ neutrophils did not suppress CD8+ T cell function. Taken together, these data demonstrate that, while neutrophils could control tumor growth by direct cytotoxic effects, the primary mechanism by which neutrophils exert antitumor effects is to regulate IL-17 production, through which they indirectly promote CD8+ T cell responses.