Psoriasis is a complex, chronic relapsing and inflammatory skin disorder with a prevalence of approximately 2% in the general population worldwide. Psoriasis can be triggered by infections, physical injury and certain drugs. The most common type of psoriasis is psoriasis vulgaris, which primarily features dry, well-demarcated, raised red lesions with adherent silvery scales on the skin and joints. Over the past few decades, scientific research has helped us reveal that innate and adaptive immune cells contribute to the chronic inflammatory pathological process of psoriasis. In particular, dysfunctional helper T cells (Th1, Th17, Th22, and Treg cells) are indispensable factors in psoriasis development. When stimulated by certain triggers, antigen-presenting cells (APCs) can release pro-inflammatory factors (IL-23, IFN-α and IL-12), which further activate naive T cells and polarize them into distinct helper T cell subsets that produce numerous cytokines, such as TNF, IFN-γ, IL-17 and IL-22, which act on keratinocytes to amplify psoriatic inflammation. In this review, we describe the function of helper T cells in psoriasis and summarize currently targeted anti-psoriatic therapies.

Background: Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. Methods: Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. Results: A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04–1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03–1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99–5.38). Conclusions: Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors. Registration: No. CRD42021259776 at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/).

Brain and muscle aryl-hydrocarbon receptor nuclear translocator like protein1 (BMAL1), a core component of circadian oscillation, is involved in many physiological activities. Increasing evidence has demonstrated the essential role of BMAL1 in reproductive physiology. For instance, BMAL1-knockout (KO) mice were infertile, with impaired reproductive organs and gametes. Additionally, in BMAL1-KO mice, hormone secretion and signaling of hypothalamus-pituitary-gonadal (H-P-G) hormones were also disrupted, indicating that H-P-G axis was impaired in BMAL1-KO mice. Moreover, both BMAL1-KO mice and BMAL1-knockdown by small interfering RNA (siRNA) in vitro cultured steroidogenic cells showed that BMAL1 was associated with gonadal steroidogenesis and expression of related genes. Importantly, BMAL1 also participates in pathogenesis of human reproductive diseases. In this review, we elaborate on the impaired reproduction of BMAL1-KO mice including the reproductive organs, reproductive endocrine hormones, and reproductive processes, highlighting the vital role of BMAL1 in fertility and reproductive endocrinology.

Background: The information of ZMYND15 in human reproduction is very limited, resulting in the unclear link between ZMYND15 variants and male infertility. Methods: Whole exome sequencing and Sanger sequencing to identify the potential pathogenic variation of ZMYND15 in infertile men, Papanicolaou staining and electron microscopy to investigate the spermatozoa morphology, western blotting and immunofluorescence staining to confirm the pathogenicity of the identified variants, and proteomic analysis and coimmunoprecipitation to clarify the potential molecular mechanism. Results: A total of 31 ZMYND15 variants were identified in 227 infertile patients. Three deleterious biallelic variants, including a novel compound heterozygous variant of c.1105delG (p.A369Qfs*15) and c.1853T>C (p.F618S), a new homozygous splicing mutation of c.1297+5G>A and a reported homozygous nonsense mutation of c.1209T>A (p.Y403*), were detected in three affected individuals with oligoasthenoteratozoospermia, showing a biallelic pathogenic mutation frequency of 1.3% (3/227). No biallelic pathogenic mutation was found in 692 fertile men. Morphology analysis showed abnormalities in sperm morphology in the patients harbouring ZMYND15 mutations. Western blotting and immunofluorescence staining confirmed the nearly absent ZMYND15 expression in the sperm of the patients. Mechanistically, ZMYND15 might regulate spermatogenesis by interacting with key molecules involved in sperm development, such as DPY19L2, AKAP4 and FSIP2, and might also mediate the expression of the autophagy-associated protein SPATA33 to maintain sperm individualisation and unnecessary cytoplasm removal. Conclusion: Our findings broaden the variant and phenotype spectrum of ZMYND15 in male infertility, and reveal the potential signalling pathway of ZMYND15 regulating spermatogenesis, finally confirming the essential role of ZMYND15 in human fertility.

: The effects of azithromycin mass drug administration (MDA) on trachoma and yaws have been addressed. However, the secondary effects of azithromycin MDA remain unclear. This study aimed to explore the secondary effects of azithromycin MDA. PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from conception to January 5, 2022. Studies on secondary effects of azithromycin MDA were included. A total of 34 studies were included. Six of them reported on child mortality, 10 on malaria, and 20 on general morbidity and condition. Azithromycin MDA reduced child mortality, and quarterly MDA may be most beneficial for reducing child mortality. The effect of azithromycin MDA on malaria was weak. No association was observed between azithromycin MDA and malaria parasitemia (rate ratio: 0.71, 95% confidence interval: 0.43–1.15). Azithromycin MDA was associated with a lower risk of respiratory tract infections and diarrhea. Additionally, it was associated with a lower risk of fever, vomiting, and headache. The carriage of pathogenic organisms such as Streptococcus pneumoniae and gut Campylobacter species was reduced. However, these secondary effects of azithromycin MDA appeared to last only a few weeks. Moreover, no association was observed between azithromycin MDA and nutritional improvement in children. In conclusion, azithromycin MDA had favorable secondary effects on child mortality and morbidity. However, the effects were short term.