[p53 regulates primordial follicle activation through the mTOR signaling pathway].

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-µ (PFT-µ, 5 µmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 µmol/L), PFT-µ (5 µmol/L), PFT-µ (5 µmol/L) + RAP (1 µmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-µ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.

Transmission of Mycobacterium tuberculosis in schools: a molecular epidemiological study using whole-genome sequencing in Guangzhou, China.

Background: China is a country with a high burden of tuberculosis (TB). TB outbreaks are frequent in schools. Thus, understanding the transmission patterns is crucial for controlling TB. Method: In this genomic epidemiological study, the conventional epidemiological survey data combined with whole-genome sequencing was used to assess the genotypic distribution and transmission characteristics of Mycobacterium tuberculosis strains isolated from patients with TB attending schools during 2015 to 2019 in Guangzhou, China. Result: The TB incidence was mainly concentrated in regular secondary schools and technical and vocational schools. The incidence of drug resistance among the students was 16.30% (22/135). The phylogenetic tree showed that 79.26% (107/135) and 20.74% (28/135) of the strains belonged to lineage 2 (Beijing genotype) and lineage 4 (Euro-American genotype), respectively. Among the 135 isolates, five clusters with genomic distance within 12 single nucleotide polymorphisms were identified; these clusters included 10 strains, accounting for an overall clustering rate of 7.4% (10/135), which showed a much lower transmission index. The distance between the home or school address and the interval time of symptom onset or diagnosis indicated that campus dissemination and community dissemination may be existed both, and community dissemination is the main. Conclusion and recommendation: TB cases in Guangzhou schools were mainly disseminated and predominantly originated from community transmission. Accordingly, surveillance needs to be strengthened to stop the spread of TB in schools.

Changes in heart rate during the peri-ictal period in focal epilepsy

Objective: We explored changes in heart rate during the peri-ictal period in patients with focal epilepsy, and differences in heart rate changes according to epileptic site and side were assessed. Methods: A total of 198 epileptic seizures in 102 patients with focal epilepsy, who had a definite epileptogenic focus and had undergone surgical treatment, were assessed from 2014 to 2019. Heart rate was measured manually during the peri-ictal period. Change in heart rate and the time it occurred were assessed and compared between different epileptic sites and sides. Results: Heart rate increased in 177 (89.4%) of 198 seizures. In 82 (44.8%) of 183 seizures, the change in heart rate occurred before seizure onset. The median period of heart rate change was seven seconds (interquartile range: 3­11 seconds) in seizures with heart rate change before seizure onset. The number of seizures with heart rate increase before seizure onset was significantly greater for medial temporal lobe epilepsy compared to lateral temporal lobe epilepsy (p=0.019) and extratemporal lobe epilepsy (p=0.002). Significance: A change in heart rate prior to seizure onset is more likely to occur in patients with medial temporal lobe epilepsy, compared to those with lateral temporal lobe epilepsy and extratemporal lobe epilepsy. Patients with medial temporal lobe epilepsy may likely benefit from seizure warning and detection devices.