Historically, a high level of estrogen in women is regarded as the signature for a longer lifespan than men. Estrogen is known to be responsible for the development and regulation of the female reproductive system and secondary sex characteristics. Ovariectomy brings on numerous complications such as early menopause, heart disease, and osteoporosis. Thus, ovariectomy impacts the long-term health and lifespan of women. However, the level of estrogen at different life stages should be managed differently. Life quality can be measured in many ways, but mainly it relates to how an individual is doing in terms of being healthy, comfortable, and able to participate in or enjoy life experiences. First of all, ovariectomy not only reduces the level of estrogen but also destroys the reproductive metabolism and potentially other metabolism functions; it may also reduce the lifespan because of the overall impact, not necessary due to the low level of estrogen. Secondly, according to the principal law of the lifespan (PLOSP), the impacts of ovariectomy at different life stages will be different. The objective of this article is to provide readers with a new view of the research on estrogen. Based on the PLOSP, we recapture the estrogen levels at different life stages and explore potential alternative approaches to the manipulation of the levels of estrogen based on the biological features of the difference life stages. Thus, a low level of estrogen in the early life stage may make a woman live longer than a woman with a normal level of estrogen. However, a low estrogen level does not equal ovariectomy. Here, we explain the different impacts of the estrogen levels during different life stages; the effects on the lifespan of the manipulation of estrogen levels at different life stages; and the differences among the estrogen levels, ovariectomy effects, life stages, and lifespan. The personalized manipulation of estrogen levels and relevant growth factors according to the characterization of the life stages may be able to extend the heathy lifespan of women.

Collagen, type III, alpha-1 (COL3A1) is essential for normal collagen I fibrillogenesis in many organs. There are differences in phenotypes of mutations in the COL3A1 gene in humans and mutations in mice. In order to investigate whether the regulation and gene network of COL3A1 is the same in healthy populations of mice and humans, we compared the quantitative trait loci (QTL) that regulate the expression level of COL3A1 and the gene network of COL3A1 pathways between humans and mice using whole genome expression profiles. Our results showed that, for the regulation of expression of Col3a1 in mice, an eQTL on chromosome (Chr) 12 regulates the expression of Col3a1. However, expression of genes in the syntenic region on human Chr 7 has no association with the expression level of COL3A1. For the gene network comparison, we identified 44 top genes whose expression levels are strongly associated with that of Col3a1 in mice. We next identified 41 genes strongly associated with the expression level of COL3A1 in humans. There are a few but significant differences in the COL3A1 gene network between humans and mice. Several genes showed opposite association with expression of COL3A1. These genes are known to play important roles in development and function of the extracellular matrix of the lung. Difference in the molecular pathway of key genes in the COL3A1 gene network in humans and mice suggest caution should be used in extrapolating results from models of human lung diseases in mice to clinical lung diseases in humans. These differences may influence the efficacy of drugs in humans whose development employed mouse models.

Introduction. To compare the effect and safety of intravitreal conbercept (IVC), intravitreal ranibizumab (IVR), or intravitreal triamcinolone acetonide (IVTA) injection on 23-gauge (23-G) pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). Methods. Fifty patients (60 eyes) of varying degrees of PDR were randomly grouped into 3 groups (1 : 1 : 1) (n=20 in each group). The 23-G PPV was performed with intravitreal conbercept or ranibizumab injection 3–7 days before surgery or intravitreal TA injection during surgery. The experiment was randomized controlled, with a noninferiority limit of five letters. Main outcome measures included BCVA, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, and silicone oil tamponade. Results. At 6 months after surgery, there were no significant differences of BCVA improvements, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, silicone oil tamponade, vitreous clear-up time, and the incidence of intraoperative bleeding between the IVC and IVR groups (all P values ≥ 0.05), but they were significantly different from the IVTA group (all P values < 0.05). IOP increases did not show significant differences between the IVC and IVR groups, but both were significantly different with the IVTA group. More patients had higher postoperative IOP in the IVTA group. Conclusions. The intravitreal injection of conbercept, ranibizumab, or TA for PDR had a significant different effect on outcomes of 23-G PPV surgery. Conbercept and ranibizumab can reduce difficulty of the operation, improve the success rate of PPV surgery, and decrease the incidence of postoperative complications.

Vitamin C (VC) is well known as an antioxidant in humans, primates and guinea pigs. Studies have suggested gender differences in VC requirements in humans, and gender differences in oxidant injury vulnerability in early life may represent a biological mechanism contributing to gender disparity in later life. Using spontaneous bone fracture (sfx) mice, which lack the gene for L-Gulonolactone oxidase (Gulo), we studied the potential sex difference in expression profiles of oxidative genes at the whole-genome level. Then, we analyzed data of gene expressions in a mouse population of recombinant inbred (RI) strains originally derived by crossing C57BL/6J (B6) and DBA/2J (D2) mice. Our data indicated that there were sex differences in the regulation of pre- and pro-oxidative genes in sfx mice. The associations of expression levels among Gulo, its partner genes and oxidative genes in the BXD (B6 × D2) RI strains showed a sex difference. Transcriptome mapping suggests that Gulo was regulated differently between female and male mice in BXD RI strains. Our study indicates the importance of investigating sex differences in Gulo and its oxidative function by using available mouse models.

Background: The greatest challenges are imposed on the overall capacity of disease management when the cases reach the maximum in each wave of the pandemic. Methods: The cases and deaths for the four waves of COVID-19 in 119 countries and regions (CRs) were collected. We compared the mortality across CRs where populations experience different economic and healthcare disparities. Findings: Among 119 CRs, 117, 112, 111, and 55 have experienced 1, 2, 3, and 4 waves of COVID-19 disease, respectively. The average mortality rates at the disease turning point were 0.036, 0.019. 0.017, and 0.015 for the waves 1, 2, 3, and 4, respectively. Among 49 potential factors, income level, gross national income (GNI) per capita, and school enrollment are positively correlated with the mortality rates in the first wave, but negatively correlated with the rates of the rest of the waves. Their values for the first wave are 0.253, 0.346 and 0.385, respectively. The r value for waves 2, 3, and 4 are −0.310, −0.293, −0.234; −0.263, −0.284, −0.282; and −0.330, −0.394, −0.048, respectively. In high-income CRs, the mortality rates in waves 2 and 3 were 29% and 28% of that in wave 1; while in upper-middle-income CRs, the rates for waves 2 and 3 were 76% and 79% of that in wave 1. The rates in waves 2 and 3 for lower-middle-income countries were 88% and 89% of that in wave 1, and for low-income countries were 135% and 135%. Furthermore, comparison among the largest case numbers through all waves indicated that the mortalities in upper- and lower-middle-income countries is 65% more than that of the high-income countries. Interpretation: Conclusions from the first wave of the COVID-19 pandemic do not apply to the following waves. The clinical outcomes in developing countries become worse along with the expansion of the pandemic.

The mouse strain BALB/c deficient in IL-1 receptor antagonist protein (Il-1ra) develops spontaneous arthritis disease (SAD) while the strain DBA/1 IL1rn -/- with the same deficiency does not. Previously, we mapped a QTL on chromosome 1 for SAD and then developed a congenic mouse strain BALB.D1-1-/- that contains the QTL genomic fragment associated with resistance from DBA/1-/- on a BALB/c-/- background. The congenic strain was relatively resistant to spontaneous arthritis and had delayed onset and reduced severity of disease. We obtained whole genome expression profiles from the spleen of the congenic strain BALB.D1-1-/- and four other strains, the wild type BALB/c, DBA/1 and the deficient DBA/1 IL1rn -/- and the BALB/c IL1rn -/-. We then compared the similarities and differences between the congenic strain and the four parental strains. Here we report the selected potential causal genes based on differential expression levels as well as function of genes. There is a considerable number of genes that are differentially expressed between the congenic strain and the three parental strains, BALB/c, DBA/1, and DBA/1-/-. However there only a few differentially expressed genes were identified by comparing the congenic strain and the BALB/c-/-strain. These differentially expressed genes are mainly from T-cell receptor beta chain (Tcrb) and interferon-activatable protein (Ifi) genes. These genes are also differentially expressed between congenic strain and BALB/c strains. However, their expression levels in the congenic strain are similar to that in DBA/1 and DBA/1-/-. The expression level of Tcrb-j gene is positively associated with two genes of Ifi gene 200 cluster. Decreased expression levels of Ifi genes is associated to the increased resistance to spontaneous arthritis disease and with down regulation of expressions of Tcrb genes in the mouse congenic strain. Ifi genes may play an important role in the susceptibility to SAD in mice.