Effect of the smartphone application on caesarean section in women with overweight and obesity: a randomized controlled trial in China.

BACKGROUND: The rate of caesarean section (CS) is increasing worldwide. While a CS can be life-saving when medically indicated, it can cause adverse health effects for both women and children. This trial aims to evaluate the effect of the smartphone application, which aims to control the gestational weight gain, on the rate of CS in overweight and obese women. METHODS: Overweight and obese primiparas (BMI ≥ 24 kg/m2) with age between 20 and 40 years old were recruited at Beijing Obstetrics and Gynecology Hospital, and randomly assigned into the intervention group (143 cases) and the control group (138 cases). The intervention group applied the smartphone application (App) to control gestational weight gain in addition to the usual care, and the control group received the usual care. Primary outcome was cesarean section (CS) rate. Secondary outcomes included gestational hypertension, preeclampsia and eclampsia, gestational diabetes mellitus, postpartum hemorrhage, neonatal asphyxia, and macrosomia. RESULTS: There was a significant difference in CS rate, with 53.3% in the intervention group and 65.4% in the control group (P = 0.044). The difference still exists in the overweight subgroup (32.6% vs. 55.6%, P = 0.04), but disappears in the obesity subgroup (63.0% vs. 69.1%, P = 0.381). The median of gestational weight gain (GWG) of the intervention group is 8.5 kg (IQR 5.5, 11.0), which is significantly less than that of the control group (median 10.0 kg, IQR [6.0, 14.0], P = 0.008). The intervention group has significantly lower rate of postpartum hemorrhage (5.19%) than the control group (12%) (P = 0.045). There were no significant differences between the groups in gestational hypertension, gestational diabetes mellitus, neonatal asphyxia, and macrosomia. CONCLUSION: The smartphone assisted weight control may help reduce CS rate. The effects of the smartphone application might be via the management of gestational weight gain. TRAIL REGISTRATION: This trial was registered at Chinese Clinical Trial Registry. Registration number is ChiCTR2300068845 (retrospectively registered, 01/03/2023).

Exploration of Serum lipid levels during twin pregnancy.

Objective: This study aims to characterize changes in serum lipid levels throughout twin pregnancies and explore the relationship between lipid levels and gestational diabetes mellitus (GDM) and hypertensive disorders complicating pregnancy (HDCP).Methods: We retrospectively studied 297 twin pregnancies of women who received regular prenatal care and delivered at the Beijing Obstetrics and Gynecology Hospital over a period of two years. Demographic and medical data of the participants were collected by questionnaires and medical records review. Serum lipid levels were measured in the first trimester (6-13 weeks), second trimester (24-28 weeks), and third trimester (34-37 weeks). A multivariate regression model was constructed to examine the association between lipid levels and pregnancy complications. A decision tree was used to explore the relationship between early serum lipid glucose levels and GDM and HDCP in twin pregnancies.Results: Triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased significantly from the first trimester to the third trimester, with the exception of high-density lipoprotein cholesterol (HDL-C), which decreased in the third trimester in twin pregnancies (p < 0.001). The levels of TC in the GDM and HDCP group were significantly elevated compared to those in the normal group in early pregnancies (p < 0.05, p < 0.05). In the second trimester, TG in the HDCP group was substantially higher than that in the normal group (p = 0.01). In the third trimester, LDL-C and HDL-C levels in the GDM group are significantly lower than that in the normal group (p < 0.05, p < 0.05). After adjusting for confounders, body mass index (BMI) is independently associated with GDM (odds ratio [OR] = 1.129, 95% confidence interval [CI]: 1.007-1.266) and HDCP(odds ratio [OR] = 1.170, 95% confidence interval [CI]: 1.031-1.329). The variation amplitude of HDL-C in the third trimester is related to the occurrence of GDM and HDCP(GDM:OR = 0.271, 95%CI: 0.095-0.778; HDCP: OR =0.249, 95% CI: 0.075-0.823). TG and TC levels in DCDA twins were significantly higher than that in MCDA twins in the first trimester(TG: p < 0.05, TC: p < 0.05). In the decision tree model for GDM, fasting blood glucose in the first trimester (FBG), TC, and pre-pregnancy BMI were identified as important nodes, while in the HDCP model, pre-pregnancy BMI, TC, and TG were key nodes.Conclusion: Serum lipid levels in twin pregnancies increase gradually during pregnancy. BMI is independently associated with the occurrence of GDM and HDCP. HDL-C may serve as a protective factor for GDM and HDCP. The predictive effect of early blood lipid on GDM and HDCP in twin pregnancy needs further study.

Biomimetic phototherapy in cancer treatment: from synthesis to application.

Phototherapy, with minimally invasive and cosmetic effect, has received considerable attention and been widely studied in cancer treatment, especially in biomaterials field. However, most nanomaterials applied for the delivery of phototherapy agents are usually recognized by the immune system or cleared by liver and kidney, thus hindering their clinical applications. To overcome these limitations, bionic technology stands out by virtue of its low antigenicity and targeting properties, including membrane bionics and bionic enzymes. In this review, we will summarize the up-to-date progress in the development of biomimetic camouflage-based nanomaterials for phototherapy, from synthesis to application, and their future in cancer treatment.

c-FLIP-Short reduces type I interferon production and increases viremia with coxsackievirus B3.

Cellular FLIP (c-FLIP) is an enzymatically inactive paralogue of caspase-8 and as such can block death receptor-induced apoptosis. However, independent of death receptors, c-FLIP-Long (c-FLIPL) can heterodimerize with and activate caspase-8. This is critical for promoting the growth and survival of T lymphocytes as well as the regulation of the RIG-I helicase pathway for type I interferon production in response to viral infections. Truncated forms of FLIP also exist in mammalian cells (c-FLIPS) and certain viruses (v-FLIP), which lack the C-terminal domain that activates caspase-8. Thus, the ratio of c-FLIPL to these short forms of FLIP may greatly influence the outcome of an immune response. We examined this model in mice transgenically expressing c-FLIPS in T cells during infection with Coxsackievirus B3 (CVB3). In contrast to our earlier findings of reduced myocarditis and mortality with CVB3 infection of c-FLIPL-transgenic mice, c-FLIPS-transgenic mice were highly sensitive to CVB3 infection as manifested by increased cardiac virus titers, myocarditis score, and mortality compared to wild-type C57BL/6 mice. This observation was paralleled by a reduction in serum levels of IL-10 and IFN-α in CVB3-infected c-FLIPS mice. In vitro infection of c-FLIPS T cells with CVB3 confirmed these results. Furthermore, molecular studies revealed that following infection of cells with CVB3, c-FLIPL associates with mitochondrial antiviral signaling protein (MAVS), increases caspase-8 activity and type I IFN production, and reduces viral replication, whereas c-FLIPS promotes the opposite phenotype.

Reduced immune response to Borrelia burgdorferi in the absence of γδ T cells.

Little is known regarding the function of γδ T cells, although they accumulate at sites of inflammation in infections and autoimmune disorders. We previously observed that γδ T cells in vitro are activated by Borrelia burgdorferi in a TLR2-dependent manner. We now observe that the activated γδ T cells can in turn stimulate dendritic cells in vitro to produce cytokines and chemokines that are important for the adaptive immune response. This suggested that in vivo γδ T cells may assist in activating the adaptive immune response. We examined this possibility in vivo and observed that γδ T cells are activated and expand in number during Borrelia infection, and this was reduced in the absence of TLR2. Furthermore, in the absence of γδ T cells, there was a significantly blunted response of adaptive immunity, as reflected in reduced expansion of T and B cells and reduced serum levels of anti-Borrelia antibodies, cytokines, and chemokines. This paralleled a greater Borrelia burden in γδ-deficient mice as well as more cardiac inflammation. These findings are consistent with a model of γδ T cells functioning to promote the adaptive immune response during infection.

Activation of gamma delta T cells by Borrelia burgdorferi is indirect via a TLR- and caspase-dependent pathway.

Activation of the innate immune system typically precedes engagement of adaptive immunity. Cells at the interface between these two arms of the immune response are thus critical to provide full engagement of host defense. Among the innate T cells at this interface are gammadelta T cells. gammadelta T cells contribute to the defense from a variety of infectious organisms, yet little is understood regarding how they are activated. We have previously observed that human gammadelta T cells of the Vdelta1 subset accumulate in inflamed joints in Lyme arthritis and proliferate in response to stimulation with the causative spirochete, Borrelia burgdorferi. We now observe that murine gammadelta T cells are also activated by B. burgdorferi and that in both cases the activation is indirect via TLR stimulation on dendritic cells or monocytes. Furthermore, B. burgdorferi stimulation of monocytes via TLR, and secondary activation of gammadelta T cells, are both caspase-dependent.

Fas ligand deficiency impairs host inflammatory response against infection with the spirochete Borrelia burgdorferi.

Lyme disease represents a complex response to Borrelia burgdorferi that involves both bacterial factors as well as host responses. This results in an inflammatory reaction at several sites, including the synovial lining of joints. Synovial tissues of inflamed joints contain cells expressing high levels of Fas and Fas ligand (FasL). Although Fas stimulation is typically associated with cell death, it can also transmit stimulatory signals to certain cell types. Among these are dendritic cells and macrophages, which are abundant in inflamed synovium. To better assess the role of FasL in the pathogenesis of Lyme arthritis, we evaluated the response to B. burgdorferi infection in C3H/HeJgld mice that bear a nonfunctional mutation in FasL. Compared to wild-type C3H+/+ mice, C3Hgld mice had a similar bacterial burden and antibody response 2 weeks and 4 weeks following infection, but they manifested a significantly reduced Borrelia-specific cytokine response. In addition, C3Hgld mice developed a greatly reduced incidence and severity of arthritis. The findings document a contribution of FasL to the host inflammatory response to B. burgdorferi.

Lyme arthritis synovial gammadelta T cells instruct dendritic cells via fas ligand.

gammadelta T cells participate in the innate immune response to a variety of infectious microorganisms. They also link to the adaptive immune response through their induction of maturation of dendritic cells (DC) during the early phase of an immune response when the frequency of Ag-specific T cells is very low. We observe that in the presence of Borrelia burgdorferi, synovial Vdelta1 T cells from Lyme arthritis synovial fluid potently induce maturation of DC, including production of IL-12, and increased surface expression of CD40 and CD86. The activated DC are then able to stimulate the Vdelta1 T cells to up-regulate CD25. Both of these processes are initiated primarily by Fas stimulation rather than CD40 activation of DC via high expression of Fas ligand by the Vdelta1 T cells. DC are resistant to Fas-induced death due to expression of high levels of the Fas inhibitor c-FLIP. This effect serves to divert Fas-mediated signals from the caspase cascade to the ERK MAPK and NF-kappaB pathways. The findings affirm the importance of the interaction of certain T cell populations with DC during the early phases of the innate immune response. They also underscore the view that as levels of c-FLIP increase, Fas signaling can be diverted from induction of apoptosis to pathways leading to cell effector function.

High expression of Fas ligand by synovial fluid-derived gamma delta T cells in Lyme arthritis.

Gamma delta T cells accumulate at epithelial barriers and at sites of inflammation in various infectious and autoimmune diseases, yet little is understood about the function of tissue-infiltrating gamma delta T cells. We observe that gamma delta T cells of the V delta 1 subset accumulate in synovial fluid of human Lyme arthritis and are intensely cytolytic toward a wide array of target cells. Particularly striking is that the cytolytic activity is highly prolonged, lasting for at least 3 wk after stimulation of the gamma delta T cells with Borrelia burgdorferi. Cytolysis is largely Fas dependent and results from very high and prolonged expression of surface Fas ligand, which is transcriptionally regulated. This also manifests in a substantial level of self-induced apoptosis of the gamma delta T cells. In this capacity, certain gamma delta T cell subsets may serve as cytolytic sentinels at sites of inflammation, and perhaps at epithelial barriers.

Gammadelta T cells promote a Th1 response during coxsackievirus B3 infection in vivo: role of Fas and Fas ligand.

Fas/Fas ligand (FasL) interactions regulate disease outcome in coxsackievirus B3 (CVB3)-induced myocarditis. MRL(+/+) mice infected with CVB3 develop severe myocarditis, a dominant CD4(+) Th1 (gamma interferon [IFN-gamma(+)]) response to the virus, and a predominance of gammadelta T cells in the myocardial infiltrates. MRL lpr/lpr and MRL gld/gld mice, which lack normal expression of Fas and express a mutated FasL, respectively, have minimal myocarditis and show a dominant CD4(+) Th2 (interleukin-4 [IL-4(+)]) phenotype to CVB3. Spleen cells from virus-infected wild-type, lpr, and gld animals proliferate equally to virus in vitro. Adoptive transfer of gammadelta T cells from hearts of CVB3-infected MRL(+/+) mice (FasL(+)) into infected MRL gld/gld recipients (FasL(-)/Fas(+)) restores both disease susceptibility and Th1 cell phenotype. However, transfer of these cells into MRL lpr/lpr recipients (FasL(+)/Fas(-)) did not promote myocarditis and the viral response remained Th2 biased. This paralleled the expression of very high surface levels of FasL by myocardial gammadelta T cells, as well as their propensity to selectively lyse Th2 virus-specific CD4(+) T cells. These results demonstrate that Fas/FasL interactions conferred by gammadelta T cells on lymphocyte subpopulations may regulate the cytokine response to CVB3 infection and pathogenicity.