Systemic lupus erythematosus(SLE) is an autoimmune disease with diverse clinical manifestations, and the mechanism of its immune disorder has not been fully defined.Previous studies have shown that type I interferon plays an important role in SLE.Type I interferon is mainly produced by macrophages and dendritic cells, and the interferon-stimulated genes in various immune cells of SLE children were significantly increased.Researchers have found that in addition to interacting with neutrophil extracellular traps, IFN-α can regulate the function of B cells, maintain and amplify autoantibodies, affect the balance of T cell subsets, ultimately aggravate autoimmune abnormalities in SLE patients.Here we review the immunological effects of type I interferon in SLE patients.

Objective:To determine the potency of epidural ropivacaine in inhibiting breakthrough pain in primiparae undergoing labor analgesia with programmed intermittent epidural bolus (PIEB).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ primiparae of full-termpregnancy, with a singleton fetus in vertex presentation, aged ≥18 yr, with body mass index < 30 kg/m 2, presenting with breakthrough pain during labor analgesia with PIEB, were enrolled in this study. Ropivacaine 10 ml was epidurally administered, and the concentration was determined by up-and-down sequential allocation. The initial concentration was set at 0.15% in the first patient in each group. Each time the concentration increased/decreased in the next patient depending on whether the patients showed breakthrough pain relief, and the ratio between the two successive doses was 0.9. The criterion of breakthrough pain relief was defined as numerical rating scale score < 4 points within 30 min after epidural injection of ropivacaine. The median effective concentration (EC 50) and 95% confidence interval of ropivacaine in inhibiting breakthrough pain were calculated by Dixon-Massey′s method. Results:Twenty-six patients were finally included in this study.The EC 50 (95% confidence interval)of ropivacaine in inhibiting breakthrough pain was 0.102% (0.088%-0.117%). Conclusions:The EC 50(95% confidence interval) of epidurally administered ropivacaine 10 ml is 0.102%(0.088%-0.117%) when used for inhibiting breakthrough pain during labor analgesia with PIEB in primiparae.

Birth cohort study has played an important role in exploring the effect of exposures in early life on long-term health of offspring. With the rapid increase of problems of reproductive health among couples at childbearing age, the assisted reproductive technology (ART) has been widely introduced into clinical practice. However, the influences of ART on long-term outcomes of mothers and infants have not been fully studied. In 2016, the China National Birth Cohort (CNBC), a multicenter prospective cohort study recruiting families with ART-conceived pregnancies and spontaneous-conceived pregnancies simultaneously was launched officially. By June 30, 2021, a total of 72 000 families covering 39 000 ART- pregnancies and 33 000 spontaneous- pregnancies have been recruited in the study, their information and biological samples were collected at multiple time points, i.e., before assisted reproductive treatment, in embryo transfer period, in first, second and third trimesters, at delivery, and at 42 days after birth, 6 months, 1 year old and 3 years old. The main objectives of this study are to assess the development and health of offspring born after ART treatment, identify risk factors associated with adverse birth outcomes and childhood diseases and provide scientific basis for the strategies to improve the quality of new birth population. This paper will give a brief introduction to the establishment and research progress of CNBC.

Background Recent advances in understanding the toxic effects of inorganic arsenic have revealed that arsenic exposure impacts multiple endocrine organs, thereby altering their functions. However, the mechanisms underlying arsenic-induced thyroid injury remain unclear. Objective To investigate the mechanisms by which sodium arsenite (NaAsO₂) affects the proliferation and apoptosis of normal thyroid cells (Nthy-ori3-1) through the estrogen receptor (ER)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods Nthy-ori3-1 cells were cultured in vitro and divided into the following groups: a control group (complete medium without drugs, 0 μmol·L⁻¹), and NaAsO₂-treated groups at 1, 2, and 4 μmol·L⁻¹. Additionally, 1 μmol·L⁻¹ of the ER inhibitor ICI182780 was used to intervene in the NaAsO₂ exposure groups, resulting in the following combinations: 1 μmol·L⁻¹ NaAsO₂ + ICI182780, 2 μmol·L⁻¹ NaAsO₂ + ICI182780, and 4 μmol·L⁻¹ NaAsO₂ + ICI182780. The median lethal concentration of NaAsO₂ was determined using cell viability assay. Cell viability was assessed at 24, 36, and 48 h using Cell Counting Kit-8 (CCK-8) assay. Colony formation ability was evaluated via plate cloning assay. Apoptosis was detected using Hoechst 33342 staining. Protein and mRNA expression levels of ERα, ERβ, c-MYC, Bax, Bcl-2, PI3K, p-PI3K, AKT, and p-AKT were measured using Western blot (WB) and real-time quantitative PCR (qRT-PCR), respectively. Results The median lethal concentration of NaAsO₂ was determined to be 4.034 μmol·L⁻¹. CCK-8 assay at 24, 36, and 48 h revealed that, compared with the control group, the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups significantly inhibited Nthy-ori3-1 cell proliferation (P < 0.001). The plate cloning assays demonstrated a concentration-dependent reduction in colony formation ability (P < 0.001). Following the ICI182780 intervention, the cell viability and colony formation ability in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups were significantly restored compared with the corresponding NaAsO₂-only groups (P < 0.001, P < 0.01). The Hoechst 33342 staining indicated that compared with the control group, the nuclear staining intensity and apoptosis levels in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups increased in a concentration-dependent manner (P < 0.001). However, the ICI182780 intervention reduced the apoptosis levels in the NaAsO₂-treated groups compared with their NaAsO₂-only counterparts (P < 0.001). The WB analysis showed that, compared with the control group, the protein expression of ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups decreased manner (P < 0.001, P < 0.01), while the Bax expression increased in a concentration-dependent (P < 0.001); the PI3K and AKT protein levels showed no significant differences (P > 0.05). In the ICI182780-treated NaAsO₂ groups, the ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT protein expression increased (P < 0.001, P < 0.01), the Bax expression decreased (P < 0.001), and the PI3K and AKT levels remained unchanged (P > 0.05) compared with the corresponding NaAsO₂-only groups. The mRNA expression patterns of ERα, ERβ, c-MYC, Bcl-2, and Bax were consistent with the WB results. Conclusion NaAsO₂ inhibits proliferation and promotes apoptosis in Nthy-ori3-1 cells in a dose-dependent manner. The underlying mechanism likely involves NaAsO₂-mediated suppression of the ER-PI3K/AKT signaling pathway, which subsequently regulates downstream proliferation- and apoptosis-related genes.

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg⁻¹ sodium arsenite (NaAsO₂)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO₂ by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg⁻¹ ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.