Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective cohort study.

STUDY QUESTION: What are the roles of maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on the embryological and clinical outcomes of IVF/ICSI? SUMMARY ANSWER: Our study reveals for the first time that the oocyte maturation potential gradually decreases with a reduction of maternal MTHFR activity determined by combined C677T/A1298C polymorphisms, while embryo quality was worse in women with intermediate MTHFR activity. WHAT IS KNOWN ALREADY: Although many previous studies have explored the association between MTHFR polymorphisms and IVF/ICSI outcomes, the results remain contradictory due to inadequate samples, no adjustment for potential confounders and/or the study of C677T and A1298C separately. Few studies have systematically investigated the exact role of MTHFR activity determined by combined C677T/A1298C polymorphisms on the embryological and clinical outcomes of IVF/ICSI. STUDY DESIGN SIZE DURATION: This is a retrospective cohort study investigating 1160 women who were referred for MTHFR genotyping and IVF/ICSI treatment at Peking University Third Hospital from May 2017 to May 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Women who were referred for MTHFR genotyping and their first IVF/ICSI treatment at our hospital were included and those undergoing preimplantation genetic testing cycles were excluded. The included women were divided into different cohorts according to their C677T, A1298C and combined C677T/A1298C genotypes. The embryological outcomes, including oocytes retrieved, metaphase II oocytes, oocyte maturation rate, normal fertilization rate and transplantable embryo rate, were evaluated by generalized linear regression models. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and live birth rate, were evaluated by log-binomial regression models. All outcomes were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Women with the combined 677TT/1298AA genotype (hereafter abbreviated as TT/AA, as with other combined genotypes), whose enzyme activity was the lowest, had a lower oocyte maturation rate compared with those with the wild-type genotype (P = 0.007). Moreover, the oocyte maturation rate decreased linearly with the decline in MTHFR enzyme activity determined by combined C677T/A1298C genotypes (P-trend = 0.001). The combined CC/AC, CC/CC&CT/AA and CT/AC genotypes with intermediate enzyme activity were associated with a lower transplantable embryo rate (P = 0.013, 0.030 and 0.039, respectively). The differences in clinical outcomes between women with wild-type genotype and combined C677T/A1298C variant genotypes were not significant. LIMITATIONS REASONS FOR CAUTION: Our study population had comparable embryological outcomes but worse clinical outcomes than other women undergoing IVF/ICSI treatment at our hospital. Therefore, the results related to the clinical outcomes should be generalized with caution. In addition, we did not detect the folate concentration of each patient during pregnancy. However, this might not have much influence on our results because almost all of our study participants took sufficient folic acid around pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on the IVF/ICSI outcomes, which can contribute to providing reasonable folic acid supplementation suggestions for women with different MTHFR genotypes, especially for those with a low oocyte maturation rate and/or low embryo quality. STUDY FUNDING/COMPETING INTERESTS: This work was funded by the National Natural Science Foundation of China (31871447, and 82101677), the National Key Research and Development Program (2019YFA0801400) and the Natural Science Foundation of Beijing Municipality (7202226). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Matrix Metalloproteinase 3: a Novel Effective Biomarker for Predicting the Mortality and the Severity of Pneumonia.

BACKGROUND: Matrix metalloproteinase 3 (MMP3) is known as an inflammatory factor; however, the effectiveness of MMP3 for diagnosis of pneumonia and predicting outcomes is unclear. We evaluated the diagnostic and prognostic value of serum MMP3 in patients with pneumonia. METHODS: One hundred and eighty-five patients with pneumonia and 52 healthy controls were enrolled. Serum MMP3, neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) concentrations were measured at admission. The patients were followed up for 90 days. RESULTS: Compared with healthy controls, the concentrations of MMP3, NGAL, and IL-6 at admission were significantly higher in patients with pneumonia (p < 0.05). The median concentrations of MMP3, NGAL, and IL-6 were significantly higher in the patients with severe pneumonia than the group of non-severe pneumonia (p < 0.05). Compared with PCT (AUC = 0.778), CRP (AUC = 0.719), and IL-6 (AUC = 0.726), MMP3 (AUC = 0.846) and NGAL (AUC = 0.826) had significantly higher AUC values for distinguishing the severity of pneumonia. The ROC of the combination of MMP3, neutrophil to lymphocyte ratio (NLR), and D-dimer showed the best performance of predicting pneumonia severity, which gave an AUC of 0.956. The AUC of MMP3 (0.950) for predicting mortality was highest, followed by NLR (AUC = 0.945), D-dimer (AUC = 0.938), and NGAL (AUC = 0.913). Multivariable logistic regression analysis showed MMP3, D-dimer, and NLR were the independent predictors of hospital mortality in patients with pneumonia. Patients with MMP3 concentration > 124.3 ng/mL had a significantly higher risk of mortality (p < 0.05). CONCLUSIONS: MMP3 is a valuable biomarker in assessment of the severity and prediction of mortality in patients with pneumonia.

[Sensitization Spectrum of 16 362 Patients with Allergic Diseases in Peking University Third Hospital].

Objective To retrospectively analyze the sensitization spectrum of 16 362 patients with allergic diseases treated in the Peking University Third Hospital and provide reference for the prevention and treatment of allergic diseases.Methods A total of 16 362 patients with allergic diseases treated in the Peking University Third Hospital from January 2009 to September 2021 were selected.The serum levels of total IgE and antigen-specific IgE(sIgE)were determined.Furthermore,the selected patients were classified into different groups according to gender,age,and disease occurrence month.Results The mean level of total IgE in 7919 patients was 92.4(34.8, 241.0)kU/L.The sIgE levels of 34 allergens in 5495 patients were determined via the ImmunoCAP system,with a positive sIgE rate of 54.23%.The top 5 allergens with high positive rates were mountain juniper pollen(43.78%),cat dander(38.76%),egg white(33.38%),Japanese hop(32.03%),and mugwort(31.82%).The sIgE levels of 20 allergens in 10 867 patients were determined via the EURO system,with a positive sIgE rate of 35.79%.The top 5 allergens with high positive rates were mugwort(15.86%),house dust mite mix(10.17%),cat dander(8.32%),house dust(4.71%),and tree pollen mix(4.04%).The analysis based on gender showed that the allergen positive rates in males were higher than those in females.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of the inhaled allergens gradually increased during 10-19 years and then gradually decreased.The analysis based on disease occurrence month showed that the population with allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens including mugwort,tree pollen mix,common ragweed,cocklebur,goosefoots,Japanese hop,timothy grass,and weed mix.Conclusions Among the 16 362 patients with allergic diseases treated in the Peking University Third Hospital,male patients showed higher sensitivity to allergens.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of inhaled allergens were highest in patients of 10-19 years.The population of allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens.

[Combination of AD5-10 and epirubicin in treating rheumatoid arthritis].

OBJECTIVE: To investigate the mechanism of anti-death receptor 5-10 (AD5-10) combined with epirubicin in treating rheumatoid arthritis (RA). METHODS: We detected the cell viability of the fibroblast-like synoviocytes (FLS) from RA patients with MTT. The expression level of apoptosis signaling pathways protein, p53, and p21 were evaluated with Western blot. RESULTS: We found that epirubicin, at different doses, could enhance the effect of AD5-10 on FLS, promoting the apoptosis of FLS. The expression levels of caspase-3, -8, -9, c-FLIP, Bcl-2, p53, and p21 in the FLS changed after epirubicin treatment. CONCLUSION: Epirubicin may coordinate with AD5-10 in inducing FLS apoptosis through affecting the levels of p53, p21, c-FLIP, and Bcl-2.