Characteristics and effects on daily lives of pelvic girdle pain during early postpartum in Beijing women, China.

Pelvic girdle pain (PGP) is a common problem during pregnancy and postpartum and negatively affects women's well-being. Yet it is not well known in China. This study assessed PGP's intensity, location, and quality and the status of daily activities on postpartum women with pain, and explored the relationship between pain and the prevalence of depressive symptoms. A cross-sectional study recruiting 1,038 eligible women at 6 weeks postpartum from the obstetric clinic of a hospital was conducted in Beijing, China. Data were collected using self-reported questionnaires, including Introductory information form, Body chart, Number Rating Scale, McGill Pain Questionnaire-2, Pelvic Girdle Questionnaire, and Edinburgh Postnatal Depression Scale. In this study, 32.2 percent women experienced pain. The mean (SD) pain intensity score was 3.07 ± 1.60. About 50.6 percent women experienced sacroiliac joint pain, and 25.5 percent women experienced pain in a combination of locations. About 73.1 percent women experienced aching pain, and 57.5 percent experienced more than one kind of pain quality. The mean total score, which assesses activity and symptom limitations, was 21.93 ± 17.35 (percent), of which a normal sex life (1.29 ± 0.94) was made more challenging due to pain. In mental health, the prevalence of depressive symptoms coincided with the prevalence of pain (p = 0.008). Postpartum PGP still needs to be taken seriously, and women with pain require further support. The above knowledge offers information to manage pain, daily lives and depressive symptoms, contributes to think about strategies to better promote postpartum women physical and mental health in the future.

Molecular Basis for SPINDOC-Spindlin1 Engagement and Its Role in Transcriptional Attenuation.

Spindlin1 is a histone reader with three Tudor-like domains and its transcriptional co-activator activity could be attenuated by SPINDOC. The first two Tudors are involved in histone methylation readout, while the function of Tudor 3 is largely unknown. Here our structural and binding studies revealed an engagement mode of SPINDOC-Spindlin1, in which a hydrophobic motif of SPINDOC, DOCpep3, stably interacts with Spindlin1 Tudor 3, and two neighboring K/R-rich motifs, DOCpep1 and DOCpep2, bind to the acidic surface of Spindlin1 Tudor 2. Although DOCpep3-Spindlin1 engagement is compatible with histone readout, an extended SPINDOC fragment containing the K/R-rich region attenuates histone or TCF4 binding by Spindlin1 due to introduced competition. This inhibitory effect is more pronounced for weaker binding targets but not for strong ones such as H3 "K4me3-K9me3" bivalent mark. Further ChIP-seq and RT-qPCR indicated that SPINDOC could promote genomic relocation of Spindlin1, thus modulate downstream gene transcription. Collectively, we revealed multivalent engagement between SPINDOC and Spindlin1, in which a hydrophobic motif acts as the primary binding site for stable SPINDOC-Spindlin1 association, while K/R-rich region modulates the target selectivity of Spindlin1 via competitive inhibition, therefore attenuating the transcriptional co-activator activity of Spindlin1.

Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome.

Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism for sustaining hepatitis B virus (HBV) life cycle and its chronic infection. HBV encodes a regulatory protein, HBx, which activates transcription and replication of HBV genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes its task by hijacking Spindlin1, an epigenetic reader comprising three consecutive Tudor domains. Our biochemical and structural studies have revealed that the highly conserved N-terminal 2-21 segment of HBx (HBx2-21) associates intimately with Tudor 3 of Spindlin1, enhancing histone H3 "K4me3-K9me3" readout by Tudors 2 and 1. Functionally, Spindlin1-HBx engagement promotes gene expression from the chromatinized cccDNA, accompanied by an epigenetic switch from an H3K9me3-enriched repressive state to an H3K4me3-marked active state, as well as a conformational switch of HBx that may occur in coordination with other HBx-binding factors, such as DDB1. Despite a proposed transrepression activity of HBx2-21, our study reveals a key role of Spindlin1 in derepressing this conserved motif, thereby promoting HBV transcription from its chromatinized genome.

Tumor-targeted delivery of a STING agonist improvescancer immunotherapy.

The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models. The STING ADC further synergized with an anti-PD-L1 antibody to achieve superior antitumor efficacy. The STING ADC promoted multiple aspects of innate and adaptive antitumor immune responses, including activation of dendritic cells, T cells, natural killer cells and natural killer T cells, as well as promotion of M2 to M1 polarization of tumor-associated macrophages. These results provided the proof of concept for clinical development of the STING ADCs.

Factors associated with poor mental health outcomes in nurses in COVID-19-designated hospitals in the postepidemic period in Guangdong Province: a cross-sectional study.

OBJECTIVE: The early days of the COVID-19 pandemic placed enormous pressure and subsequent negative psychological problems on nurses, but at this stage of the year-long COVID-19 outbreak, the level of stress and negative emotions that nurses experience is unclear. Our study attempted to assess the factors influencing mental health status in nurses during the postepidemic period of COVID-19. DESIGN: Cross-sectional study. SETTING: COVID-19 designated hospitals. PARTICIPANTS: 1284 Chinese nurses. MAIN OUTCOME MEASURES: Electronic questionnaires, including the Chinese version of the Perceived Stress Scale (CPSS) and Symptom Checklist-90 (SCL-90), were distributed for self-evaluation. Regression analysis was used to analyse the associated factors of psychological stress among variables such as age, years of nursing experience, weekly working hours, anxiety symptoms, somatisation symptoms and compulsive symptoms. RESULTS: A total of 1284 respondents from COVID-19-designated hospitals in Guangdong Province were studied. The average CPSS score for all respondents was 22.91±7.12. A total of 38.5% of respondents scored ≥26 on the CPSS, indicating a significant degree of psychological stress. Nurses with high psychological stress had higher levels of anxiety symptoms (41.7% vs 8.0%), somatisation symptoms (31.4% vs 7.7%) and compulsion symptoms (62.3% vs 27.0%) than nurses with low psychological stress. Stepwise multiple linear regression revealed that weekly working hours, years of nursing experience, anxiety symptoms, somatisation symptoms and compulsion symptoms had a linear relationship with the participants' psychological stress scores. CONCLUSION: Nurses experienced significant physical and psychological risk while working in the postepidemic period. Our findings suggest that nurses still need support to protect their physical and mental health.

Effects of Diet and Exercise Interventions to Prevent Gestational Diabetes Mellitus in Pregnant Women With High-Risk Factors in China: A Randomized Controlled Study.

This is a randomized controlled study to determine whether diet and exercise interventions can reduce the incidence of gestational diabetes mellitus (GDM) in pregnant women with high-risk factors. Ninety-four pregnant women were randomly divided into the intervention (n = 47) and control (n = 47) groups. A diet and exercise program was provided for the intervention group by researchers and was adjusted every 2 weeks by outpatient or WeChat intervention. The control group only received the routine health management in the hospital. Follow-up continued until the birth of the baby. The incidence of GDM (23.9%) in the intervention group was lower than in the control group (51.1%) (p = .007). Weight gain did not differ significantly between the two groups throughout pregnancy (p = .572). It is concluded that diet and exercise interventions can reduce the incidence of GDM in pregnant women with high-risk factors.

Probiotics for preventing gestational diabetes in overweight or obese pregnant women: A review.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Specific probiotics or probiotic foods can be used to reduce the risk of diseases associated with aberrant gut microbiota composition. The incidence of gestational diabetes mellitus (GDM) has increased annually with the proportion of overweight and obese people. Overweight or obese pregnant women are at high risk of GDM and have obvious changes in gut microbiota compared with normal-weight pregnant women. Specific probiotics or probiotic foods may alter gut microbiota in overweight or obese pregnant women and inhibit the expression of inflammatory factors, consequently resulting in weight loss and reduced insulin resistance. This review discusses the mechanism of probiotics on GDM, as well as the dose, method and duration of probiotics use, and summarizes current evidence on probiotics in improving glucose metabolism and other maternal and infant outcomes in overweight/obese pregnant women.

Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity.

Telomerase is an attractive target for anti-tumor therapy as it is almost universally expressed in cancer cells. Here, we show that treatment with a telomere-targeting drug, 6-thio-2'-deoxyguanosine (6-thio-dG), leads to tumor regression through innate and adaptive immune-dependent responses in syngeneic and humanized mouse models of telomerase-expressing cancers. 6-thio-dG treatment causes telomere-associated DNA damages that are sensed by dendritic cells (DCs) and activates the host cytosolic DNA sensing STING/interferon I pathway, resulting in enhanced cross-priming capacity of DCs and tumor-specific CD8+ T cell activation. Moreover, 6-thio-dG overcomes resistance to checkpoint blockade in advanced cancer models. Our results unveil how telomere stress increases innate sensing and adaptive anti-tumor immunity and provide strong rationales for combining telomere-targeting therapy with immunotherapy.