Disruption of ZNF334 promotes triple-negative breast carcinoma malignancy through the SFRP1/ Wnt/ß-catenin signaling axis.

Zinc-finger proteins (ZNFs) constitute the largest transcription factor family in the human genome. The family functions in many important biological processes involved in tumorigenesis. In our research, we identified ZNF334 as a novel tumor suppressor of triple-negative breast cancer (TNBC). ZNF334 expression was usually reduced in breast cancerv (BrCa) tissues and TNBC cell lines MDA-MB-231 (MB231) and YCCB1. We observed that promoter hypermethylation of ZNF334 was common in BrCa cell lines and tissues, which was likely responsible for its reduced expression. Ectopic expression of ZNF334 in TNBC cell lines MB231 and YCCB1 could suppress their growth and metastatic capacity both in vitro and in vivo, and as well induce cell cycle arrest at S phase and cell apoptosis. Moreover, re-expression of ZNF334 in TNBC cell lines could rescue Epithelial-Mesenchymal Transition (EMT) process and restrain stemness, due to up-regulation of SFRP1, which is an antagonist of Wnt/ß-catenin signaling. In conclusion, we verified that ZNF334 had a suppressive function of TNBC cell lines by targeting the SFRP1/Wnt/ß-catenin signaling axis, which might have the potentials to become a new biomarker for diagnosis and treatment of TNBC patients.

ZBTB28 inhibits breast cancer by activating IFNAR and dual blocking CD24 and CD47 to enhance macrophages phagocytosis.

Breast cancer is the leading cause of cancer death in female. Until now, advanced breast cancer is still lack effective treatment strategies and reliable prognostic markers. In the present article, we introduced the physiologic and pathologic functions and regulation mechanisms of ZBTB28, a tumor suppressor gene, in breast cancer. ZBTB28 is frequently silenced in breast cancer due to promoter CpG methylation, and its expression is positively correlated with breast cancer patient survival. The antineoplastic effect of ZBTB28 in breast cancer was elucidated through a series of in vitro and in vivo measurements, including cell proliferation, apoptosis, cell cycle, epithelial mesenchymal transition (EMT), and growth of xenografts. Furthermore, ZBTB28 can directly regulate IFNAR to activate interferon-stimulated genes and potentiate macrophage activation. Ectopic ZBTB28 expression in breast cancer cells was sufficient to downregulate CD24 and CD47 to promote phagocytosis of macrophages, demonstrating that ZBTB28 was beneficial for the combination treatment of anti-CD24 and anti-CD47. Collectively, our results reveal a mode of action of ZBTB28 as a tumor suppressor gene and suggest that ZBTB28 is an important regulator of macrophage phagocytosis in breast cancer, holding promise for the development of novel therapy strategies for breast cancer patients.

Structural family factors and bullying at school: a large scale investigation based on a Chinese adolescent sample.

BACKGROUNDS: Various family factors have been identified in association with school bullying and the involvement of children and adolescents in bullying behaviors. METHODS: A total of 11,919 participants (female = 6671, mean age = 15) from 22 middle schools in Suzhou City, China completed the questionnaire. The associations between structural family factors (family socio-economic status, living arrangement, number of siblings, whether they were local residents/migrants, had an urban/rural hukou [a household registration system in China], parental and maternal education levels, and other various bullying-related constructs (i.e. bullying witnessing, bullying involvement, bystander intervention, and fear of being bullied) were all examined. Odds ratios (ORs) adjusted for covariates were calculated for the four bullying-related constructs (bullying witness, bullying involvement, bystander intervention, and reactions to being bullied) using structural family factors. RESULTS: The result showed that all demographic household characteristics were associated with bullying at school except for being from a single-child family. Adolescents from rural families witnessed more bullying incidents than those from local families (OR = 1.35, 95% CI: [1.09, 1.68]). Adolescents who come from migrant families (OR = 1.12, 95% CI: [1.07, 1.43]) with a rural hukou (OR = 1.31, 95% CI: [1.00, 1.74]) and low parental education levels (OR = 1.42, 95% CI: [1.01, 2.57]) were more likely to be bullies. Adolescents who came from migrant families (OR = 1.37, 95% CI: [1.03, 1.82]), with low maternal education levels (OR = 1.42, 95% CI: [1.06, 1.91]) engaged in more negative bystander intervention behaviors. Furthermore, adolescents with less educated mothers experienced a higher fear of being bullied (never versus sometimes: OR = 1.33, 95% CI: [1.00, 1.85]; never versus usually OR = 1.39, 95% CI: [1.01, 1.20]). CONCLUSIONS: A systematic examination of the relationship between school bullying and demographic household characteristics may be used to inform school policies on bullying, such as training management on the importance of paying attention to adolescents from disadvantage household backgrounds. Identifying demographic factors that may predict bullying can also be used to prevent individuals from becoming involved in bullying and reduce the related negative consequences from being bullied.

Postpartum depression in mothers and fathers: a structural equation model.

BACKGROUND: Post-partum depression (PPD) is a growing mental health concern worldwide. There is little evidence in the Chinese context of the relationship between paternal PPD and maternal PPD. Given the growing global concerns this relationship requires further exploration. METHODS: A survey was conducted with 950 total couples from March 2017 to December 2018. The study was conducted using a standardized questionnaire that included basic demographic information, information on the relationship between the mother-in-law and daughter-in-law, marital satisfaction (both maternal and paternal), and PPD symptoms. Structural Equation Modelling (SEM) analysis was used to explore the underlying mechanism for PPD symptoms in mothers and fathers. RESULTS: In 4.4% of the couples both the wife and the husband showed depressive symptoms. Maternal marital satisfaction showed a significant mediating effect on paternal PPD (B = -0.114, p < 0.01), and there was a direct effect of maternal PPD on paternal PPD (B = 0.31, p < 0.001). CONCLUSIONS: This is the first study to investigate the possible correlation between maternal PPD, mother-in-law and daughter-in-law relationship satisfaction, maternal marital satisfaction, paternal marital satisfaction, and paternal PPD. It is important for future PPD interventions to target both maternal and paternal mental health, as well as the mechanisms identified that can lead to PPD.

Randomized, controlled trial comparing laryngeal mask versus endotracheal intubation during neonatal resuscitation---a secondary publication.

BACKGROUND: This study aimed to study the feasibility, efficacy and safety of using laryngeal mask (LM) ventilation compared with endotracheal intubation (ETI) during neonatal resuscitation. METHODS: Neonates with a heart rate below 60 beats per minute despite 30 s of face mask ventilation were assigned quasi-randomly (odd/even birth date) to LM (n = 36) or ETI (n = 32) ventilation. Differences in first attempt insertion success, insertion time, Apgar score, resuscitation outcome, and adverse effects were compared. RESULTS: There were no significant differences in first attempt at successful insertion (LM, 94.4 % vs. ETI, 90.6 %), insertion time (LM, 7.58 ± 1.16 s vs. ETI, 7.89 ± 1.52 s), Apgar score at 1 and 5 min, response time, ventilation time, successful resuscitation (LM, 86.1 % vs. ETI,  96.9 %), and adverse events (LM, n =3 vs. ETI, n =4) between groups. CONCLUSIONS: Laryngeal mask ventilation is an effective alternative to endotracheal intubation during resuscitation of depressed newborns who do not respond to face-mask ventilation. During an emergency, laryngeal mask ventilation may be a preferred technique for medical staff who are unable to acquire or maintain endotracheal intubation skills. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-IOQ-15006488. Registered on 2 June 2015.

Guanylate-Binding Protein 1 (GBP1) Enhances IFN-α Mediated Antiviral Activity against Hepatitis B Virus Infection.

Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-α antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFNα-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFNα-2b further increased the antiviral effect of IFN-α, while GBP1 silencing co-treatment with Peg-IFNα-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFNα-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFNα-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-α induced immune responses in response to HBV.

Development and Validation of a Novel Prognosis Model Based on a Panel of Three Immunogenic Cell Death-Related Genes for Non-Cirrhotic Hepatocellular Carcinoma.

Purpose: The accurate prediction of non-cirrhotic hepatocellular carcinoma (NCHCC) risk facilitates improved surveillance strategy and decreases cancer-related mortality. This study aimed to explore the correlation between immunogenic cell death (ICD) and NCHCC prognosis using The Cancer Genome Atlas (TCGA) datasets, and the potential prognostic value of ICD-related genes in NCHCC. Methods: Clinical and transcriptomic data of patients with NCHCC patients were retrieved from TCGA database. Weighted gene co-expression network analysis was performed to obtain the NCHCC phenotype-related module genes. Consensus clustering analysis was performed to classify the patients into two clusters based on intersection genes among differentially expressed genes (DEGs) between cancer and adjacent tissues, NCHCC phenotype-related genes, and ICD-related genes. NCHCC-derived tissue microarray was used to evaluate the correlation of the expression levels of key genes with NCHCC prognosis using immunohistochemical staining. Results: Cox regression analyses were performed to construct a prognostic risk score model comprising three genes (TMC7, GRAMD1C, and GNPDA1) based on DEGs between two clusters. The model stratified patients with NCHCC into two risk groups. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. Univariable and multivariable Cox regression analyses revealed that these signature genes are independent predictors of OS. Functional analysis revealed differential immune status between the two risk groups. Next, a nomogram was constructed, which demonstrated the potent distinguishing ability of the developed model based on receiver operating characteristic curves. In vitro functional validation revealed that the migration and invasion abilities of HepG2 and Huh7 cells were upregulated upon GRAMD1C knockdown but downregulated upon TMC7 knockdown. Conclusion: This study developed a prognostic model comprising three genes, which can aid in predicting the survival of patients with NCHCC and guide the selection of drugs and molecular markers for NCHCC.

Thoracoscopic approach to the resection of idiopathic azygos vein aneurysm: a case report.

BACKGROUND: Azygos vein aneurysm (AVA) is a rare thoracic pathological entity that mimics a posterior mediastinal mass. However, the pathogenesis of primary azygos vein aneurysms is not clear and its pathology is still being discussed. Some of the AVA are asymptomatic and usually discovered accidentally by routine physical examination. CASE PRESENTATION: We report the case of a 37-year-old woman who had an azygos vein arch aneurysm with no obvious clinical symptoms. With the analysis of clinical features of the case and AVA morphological characteristics, the AVA was found by a chest computed tomography. Then, enhanced chest computed tomography showed a soft-tissue mass (4.9 × 3.7 × 3.2 cm) in the right posterior mediastinum, which was connected to the superior vena cava and significantly enhanced with contrast agent stratification. The density of the tumor in the delayed stage was the same as that in the azygos vein. The patient underwent video-assisted thoracoscopic surgery. Histopathological evaluation of the surgical biopsy specimen proved to be a completely thrombosed aneurism of the azygos vein arch. CONCLUSIONS: AVA is a rare pathology that must be taken into consideration during the differential diagnosis of right posterior mediastinal masses. Thoracoscopic surgery is one of the most preferred treatment options for azygos vein aneurysm.

Comprehensive sequence and expression profile analysis of the phosphate transporter gene family in soybean.

The family of phosphate transporters (PHTs) mediates the uptake and translocation of Pi inside the plants. However, little is known about transporters in soybean. Therefore, Searched the Genome Database for Soybean, 57 GmPHTs family members were identified in soybean, Phylogenetic analysis suggested that members of the PHTs gene family can be divided into six clades. Collinearity analysis revealed that most of the GmPHT genes shared syntenic relationships with PHTs members in Arabidopsis thaliana and that large segment duplication played a major driving force for GmPHTs evolution in addition to tandem duplication. Further analysis of the promoter revealed that light-responsive elements and abiotic stress-responsive elements were widely distributed within the promoter regions of GmPHT genes. Based on RNA-seq data, GmPHTs showed different expression patterns in roots and leaves of soybean treated with long-term low phosphorus and short-term low phosphorus, in addition, the expression levels of GmPHT genes can be regulated by drought stresses, it was implied that the induced expression of GmPHTs could promote phosphorus uptake and transport in soybean and thus adapt to low phosphorus and drought stress, which is the first step dissection of Pi transport system and probably refers to new roles of PHTs genes in soybean.

KLF15 suppresses tumor growth and metastasis in Triple-Negative Breast Cancer by downregulating CCL2 and CCL7.

Kruppel like factor 15 (KLF15), a transcriptional factor belonging to the Kruppel-like factor (KLF) family of genes, has recently been reported as a tumor suppressor gene in breast cancer. However, the specific mechanisms by which KLF15 inhibits BrCa have not been elucidated. Here we investigated the role and mechanism of KLF15 in triple-negative breast cancer (TNBC). KLF15 expression and methylation were detected by RT-qPCR, RT-PCR and methylation-specific PCR in breast cancer cell lines and tissues. The effects of KLF15 on TNBC cell functions were examined via various cellular function assays. The specific anti-tumor mechanisms of KLF15 were further investigated by RNA sequence, RT-qPCR, Western blotting, luciferase assay, ChIP, and bioinformatics analysis. As the results showed that KLF15 is significantly downregulated in breast cancer cell lines and tissues, which promoter methylation of KLF15 partially contributes to. Exogenous expression of KLF15 induced apoptosis and G2/M phase cell cycle arrest, suppressed cell proliferation, metastasis and in vivo tumorigenesis of TNBC cells. Mechanism studies revealed that KLF15 targeted and downregulated C-C motif chemokine ligand 2 (CCL2) and CCL7. Moreover, transcriptome and metabolome analysis revealed that KLF15 is involved in key anti-tumor regulatory and metabolic pathways in TNBC. In conclusion, KLF15 suppresses cell growth and metastasis in TNBC by downregulating CCL2 and CCL7. KLF15 may be a prognostic biomarker in TNBC.

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis.

BACKGROUND: Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment. METHODS: Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo. RESULTS: This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200. CONCLUSION: These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.

COPB2 promotes metastasis and inhibits apoptosis of lung adenocarcinoma cells through functioning as a target of miR-216a-3p.

BACKGROUND: Lung adenocarcinoma is a non-small cell lung cancer with a high mortality. There is little published data on the role of coatomer protein complex subunit ß (COPB2) in lung adenocarcinoma. The current study aimed to explore the effects of COPB2 on lung adenocarcinoma cells. METHODS: The differential expression of COPB2 in normal cells and lung adenocarcinoma cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR) and Western blotting. Then, cell viability assay, flow cytometry and Transwell experiments were performed to study the effects of COPB2 on cell growth, apoptosis, migration and invasion. MiRNA targeting COPB2 was predicted by TargetScan and validated by luciferase assay, qRT-PCR and Western blotting. The effects of miRNA inhibitor on siCOPB2 were analyzed by rescue experiments. Finally, apoptosis and metastatic marker proteins were detected by Western blotting. RESULTS: COPB2 was high-expressed in lung adenocarcinoma cells. Silencing COPB2 inhibited cell viability and cell metastasis, and significantly increased apoptosis. MiR-216a-3p was predicted to be able to target COBP2. Rescue experiment showed that miR-216a-3p inhibitor promoted cell viability, migration and invasion, and inhibited apoptosis of lung adenocarcinoma cells, partly reversed the effects of siCOPB2. Moreover, Western blotting showed that siCOPB2 up-regulated expressions of cleaved Caspase-3, Caspase-3, BCL2 associated X (Bax), and E-Cadherin, and down-regulated expressions of BCL2 apoptosis regulator (Bcl-2), N-Cadherin, and Vimentin, and the above effects were also partly reversed by miR-216a-3p inhibitor. CONCLUSIONS: High-expressed COPB2 promotes metastasis and inhibits apoptosis of lung adenocarcinoma cells through functioning as a target of miR-216a-3p.

Arabidopsis thalianaMLK3, a Plant-specific Casein Kinase 1, Negatively Regulates Flowering and Phosphorylates Histone H3 in Vitro.

Arabidopsis thaliana MUT9-like kinases (MLKs), a family of the plant-specific casein kinase 1 (CK1), have been implicated collectively in multiple biological processes including flowering. Three of the four MLKs (MLK1/2/4) have been characterized, however, little is known about MLK3, the most divergent member of MLKs. Here, we demonstrated that disruption of MLK3 transcript in mlk3 caused early flowering with retarded leaf growth under long-day conditions. In vitro kinase assay showed the nuclear protein MLK3 phosphorylated histone 3 at threonine 3 (H3T3) and mutation of a conserved residue (K146R) abolished the catalytic activity. Ectopic expression of MLK3 but not MLK3(K146R) rescued the morphological defects of mlk3, indicating that an intact MLK3 is critical for maintaining proper flowering time. Transcriptomic analysis revealed that the floral repressor FLOWERINGLOCUS C (FLC) was down-regulated significantly in mlk3, suggesting that MLK3 negatively regulates flowering. Hence, MLK3 plays a role in repressing the transition from vegetative to reproductive phase in A. thaliana. This study sheds light on the delicate control of flowering time by A. thaliana CK1 specific to the plant kingdom.

Mental Health Status of Cisgender and Gender-Diverse Secondary School Students in China.

Importance: Transgender or gender nonconforming (TGNC) adolescents face a wide range of physical and mental health concerns. However, there has been no school-based study to explore the prevalence and mental health status of these adolescents in mainland China. Objectives: To assess the mental well-being of TGNC adolescents in China by comparing them with their cisgender peers. Design, Setting, and Participants: This was a cross-sectional survey study. Of the 12 354 adolescents who completed the questionnaire, 246 did not specify to which sex they identified and were therefore excluded from further analysis. Therefore, a total of 12 108 adolescents were included from 18 secondary schools in Suzhou city, China, from June 2019 to July 2019. Participants provided consent and answered questions on sex assigned at birth and gender identity. Main Outcomes and Measures: All participants completed questionnaires, including the Patient Health Questionnaire for the measurement of depressive symptoms, a generalized anxiety disorder screening, the Pittsburgh Sleep Quality Index, and a self-harm and suicide risk checklist. The frequency of being bullied at school was also measured. Participants who reported their perceived gender as the opposite of their assigned sex at birth were classified as transgender, those who identified as neither male nor female were classified as nonbinary, and those who were not sure about their perceived gender were classified as questioning. All of these participants were categorized as TGNC adolescents. Results: A total of 12 108 adolescents (mean [SD] age, 15.8 [1.0] years; 6518 [53.8%] assigned male at birth [AMAB]) participated in the study. Of the 6518 participants AMAB in the sample, 5855 (89.8%) were classified as cisgender boys, 208 (3.2%) as transgender girls (transgender youth who perceive their current gender identity to be female), 138 (2.1%) as nonbinary youth AMAB, and 317 (4.9%) as questioning youth AMAB. Of the 5590 participants assigned female at birth (AFAB), 4142 (74.1%) were classified as cisgender girls, 861 (15.4%) as transgender boys (transgender youth who perceive their current gender identity to be male), 112 (2.0%) as nonbinary youth AFAB, and 475 (8.5%) as questioning youth AFAB. Compared with cisgender adolescents, TGNC adolescents reported significantly higher health concerns including lower overall health (t11 872 = -7.36; P < .001), poorer sleep (t11 683 = 10.49; P < .001), higher depression and anxiety symptoms (t11 830 = 12.43 and t11 847 = 11.47, respectively; P < .001), and higher rate of self-harm and suicide ideation (t11 860 = 12.22; P < .001). The TGNC youth who were AMAB were also more likely to be bullied at school than cisgender boys (transgender girls: odds ratio [OR], 2.34 [95% CI, 1.64-3.33]; nonbinary youth AMAB: OR, 1.97 [95% CI, 1.23-3.16]; and questioning youth AMAB: OR, 1.95 [95% CI, 1.43-2.67]). The TGNC groups also reported significantly greater amounts of thoughts of self-harm (transgender girls: OR, 3.06 [95% CI, 2.24-4.19]; transgender boys: OR, 4.06 [95% CI, 3.47-4.74]; nonbinary youth AMAB: OR, 2.86 [95% CI, 1.93-4.23]; nonbinary youth AFAB: OR, 3.71 [95% CI, 2.46-5.59]; questioning youth AMAB: OR, 2.61 [95% CI, 1.98-3.44]; and questioning youth AFAB: OR, 3.35 [95% CI, 2.70-4.16]), thoughts of suicide (transgender girls: OR, 3.93 [95% CI, 2.88-5.38]; transgender boys: OR, 3.71 [95% CI, 3.10-4.21]; nonbinary youth AMAB: OR, 3.13 [95% CI, 2.11-4.63]; nonbinary youth AFAB: OR, 3.78 [95% CI, 2.50-5.71]; questioning youth AMAB: OR, 2.53 [95% CI, 1.93-3.33]; and questioning youth AFAB: OR, 3.94 [95% CI, 3.17-4.88]), suicide plan formation (transgender girls: OR, 4.44 [95% CI, 2.88-6.83]; transgender boys: OR, 2.66 [95% CI, 2.03-3.50]; nonbinary youth AMAB: OR, 5.36 [95% CI, 3.22-8.93]; nonbinary youth AFAB: OR, 4.06 [95% CI, 2.25-7.30]; and questioning youth AFAB: OR, 2.36 [95% CI, 1.63-3.43]), deliberate self-harm during the last month (cisgender girls: OR, 1.49 [95% CI, 1.33-1.68]; transgender girls: OR, 2.74 [95% CI, 1.93-3.91]; transgender boys: OR, 3.06 [95% CI, 2.57-3.66]; nonbinary youth AMAB: OR, 2.56 [95% CI, 1.66-3.94]; nonbinary youth AFAB: OR, 3.06 [95% CI, 1.95-4.81]; questioning youth AMAB: OR, 2.14 [95% CI, 1.56-2.92]; and questioning youth AFAB: OR, 2.53 [95% CI, 2.00-3.01]), and attempts of suicide (transgender girls: OR, 4.35 [95% CI, 2.88-6.56]; transgender boys: OR, 2.92 [95% CI, 2.26-3.76]; nonbinary youth AMAB: OR, 3.94 [95% CI, 2.36-6.55]; nonbinary youth AFAB: OR, 3.06 [95% CI, 1.67-5.63]; questioning youth AMAB: OR, 2.61 [95% CI, 1.73-3.94]; and questioning youth AFAB: OR, 1.93 [95% CI, 1.33-2.81]) compared with cisgender boys. Conclusions and Relevance: Results of this cross-sectional survey study suggest poor mental health status among TGNC adolescents in China; in addition, findings suggest a compelling need for researchers, practitioners, and policy makers to address these mental health problems. Particular school-based interventions are recommended to support the mental health well-being of TGNC adolescents.

BTB/POZ zinc finger protein ZBTB16 inhibits breast cancer proliferation and metastasis through upregulating ZBTB28 and antagonizing BCL6/ZBTB27.

BACKGROUND: Breast cancer remains in urgent need of reliable diagnostic and prognostic markers. Zinc finger and BTB/POZ domain-containing family proteins (ZBTBs) are important transcription factors functioning as oncogenes or tumor suppressors. The role and regulation of ZBTB16 in breast cancer remain to be established. METHODS: Reverse-transcription PCR and methylation-specific PCR were applied to detect expression and methylation of ZBTB16 in breast cancer cell lines and tissues. The effects of ZBTB16 in breast cancer cells were examined via cell viability, CCK8, Transwell, colony formation, and flow cytometric assays. Xenografts and immunohistochemistry analyses were conducted to determine the effects of ZBTB16 on tumorigenesis in vivo. The specific mechanisms of ZBTB16 were further investigated using Western blot, qRT-PCR, luciferase assay, and co-IP. RESULTS: ZBTB16 was frequently downregulated in breast cancer cell lines in correlation with its promoter CpG methylation status. Restoration of ZBTB16 expression led to induction of G2/M phase arrest and apoptosis, inhibition of migration and invasion, reversal of EMT, and suppression of cell proliferation, both in vitro and in vivo. Furthermore, ectopically expressed ZBTB16 formed heterodimers with ZBTB28 or BCL6/ZBTB27 and exerted tumor suppressor effects through upregulation of ZBTB28 and antagonistic activity on BCL6. CONCLUSIONS: Low expression of ZBTB16 is associated with its promoter hypermethylation and restoration of ZBTB16 inhibits tumorigenesis. ZBTB16 functions as a tumor suppressor through upregulating ZBTB28 and antagonizing BCL6. Our findings also support the possibility of ZBTB16 being a prognostic biomarker for breast cancer.

Mental health outcomes among Chinese prenatal and postpartum women after the implementation of universal two-child policy.

BACKGROUND: Poor mental health status among both pregnant and postpartum women is commonly reported worldwide. The associations between mental health outcomes and giving birth to the second child since the implementation of China's universal two-child policy have not been identified. METHODS: A large-scale based mental health survey was conducted between March 2017 and December 2018 in Suzhou, China. The survey evaluated the symptoms of anxiety, hypomania, depression and poor sleep quality among both pregnant and postpartum women. RESULTS: A total of 3113 questionnaires were collected, the prevalence of anxiety, hypomanic and depressive symptoms and poor sleep quality in our sample were 3.2% (95%CI: 2.6%-3.9%), 51.7% (95%CI: 49.9%-53.4%), 12.4% (95%CI: 11.3%-13.6%) and 37.8% (95%CI: 36.0%-39.5%), respectively. Logistic regression showed that giving birth to the second child was positively associated with women's age, and was negatively correlated with higher educational level and living in rented housing. Women with the second pregnancy or child were positively associated with anxiety symptoms in the whole sample (OR = 1.75, 95%CI: 1.11-2.75) and among prenatal women (OR = 2.11, 95%CI: 1.16-3.83), while it was inversely correlated with depressive symptoms among postpartum women (OR = 0.63, 95%CI: 0.41-0.99). CONCLUSIONS: Women giving birth a second time were more prone to have anxiety symptoms among the prenatal women and the whole sample, and less likely to have depressive symptoms among the postpartum women. Efficacious measures and interventions are essential to improve maternal mental health.

Screening for postpartum hypomania among Chinese women after childbirth.

This study examines the prevalence and risk factors for postpartum hypomania in women after childbirth as well as examining the potential influence of personality traits in relation to experiencing symptoms of postpartum hypomania. A total of 1022 women no later than 1 month post-birth were recruited in Suzhou, China, between March 2017 and December 2018. Hypomanic symptoms were assessed with the Hypomania Checklist-32 (HCL-32), and a total score of 14 or higher was defined as having hypomanic symptoms. We found 43.6% of the women in our sample had hypomanic symptoms. The results of multiple logistic regression showed that rural residence [p = 0.01, odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.5-0.9], education background (p = 0.005, OR = 0.6, 95% CI = 0.5-0.9), marriage satisfaction (p = 0.048, OR = 0.9, 95% CI =0.8-1.0), Pittsburgh Sleep Quality Index (PSQI) (p = 0.001, OR = 0.9, 95% CI = 0.9-1.0), Eysenck Personality Questionnaire-Extraversion (p < 0.001, OR = 1.2, 95% CI = 1.1-1.2), Eysenck Personality Questionnaire-Lie (p = 0.01, OR = 0.9, 95% CI = 0.9-1.0), and General Anxiety Disorder-7 (p = 0.02, OR = 1.1, 95% CI = 1.0-1.1) were independently associated with exhibiting hypomanic symptoms. The current study provided insights into hypomanic symptoms in Chinese postpartum women. We also found that extraversion and lie personality were significantly associated with an increased risk of hypomanic symptoms in postpartum women. It is urgent to arrange screening for women at risk of developing postpartum hypomania as soon as possible after giving birth and at regular intervals in the first 6 months to prevent the women developing psychological disorders such as depression and bipolar disorder later on.

Relationship between trait neuroticism and suicidal ideation among postpartum women in China: Testing a mediation model.

BACKGROUND: Suicidal ideation is a common phenomenon among postpartum women around the world. However, evidence of the relationship between neuroticism and suicidal ideation among postpartum women is still lacking. METHODS: From March 2017 to December 2018, a total of 1027 postpartum women (assessed no later than one month post-birth) were recruited to complete questionnaires assessing neuroticism, depression, anxiety and suicidal ideation. RESULTS: Anxiety and depression fully mediated the association between neuroticism and suicidal ideation (Total indirect effects = 0.11, 95%CI: 0.07, 0.15). The indirect effect of the pathway of EPQ (Neuroticism)-Anxiety-Suicidal ideation was more significant than other pathways (Indirect effects=0.04, 95%CI: 0.02, 0.07). CONCLUSION: Interventions for suicidal ideation in postpartum women need to target neuroticism and further research is necessary understand the mechanisms by which neuroticism affects suicidal ideation.

The impact of an intervention package promoting effective neonatal resuscitation training in rural China.

OBJECTIVE: To evaluate an intervention package promoting effective neonatal resuscitation training at county level hospitals across China. METHODS: The intervention package was implemented across 4 counties and included expert seminars, training workshops, establishment of hospital-based resuscitation teams, and supervision of training by national and provincial instructors. Upon completing the activities, a survey was conducted in all county hospitals in the 4 intervention counties and 4 randomly selected control counties. Data on healthcare providers' knowledge and self-confidence, and incidence of deaths from birth asphyxia from 2009 to 2011 in all hospitals were collected and compared between the two groups. RESULTS: Eleven intervention and eleven control hospitals participated in the evaluation, with 97 and 87 health providers, respectively, completing the questionnaire survey. Over 90% of intervention hospitals had implemented neonatal resuscitation related practice protocols, while in control hospitals the proportion was less than 55%. The average knowledge scores of health providers in the intervention and control counties taking a written exam were 9.2±1.2 and 8.4±1.5, respectively (P<0.001) out of maximum possible score of 10, and the average self-confidence scores were 57.3±2.5 and 54.1±8.2, respectively (P<0.001). Incidence of birth asphyxia (defined as 1-min Apgar score≤7) decreased from 8.8% to 6.0% (P<0.001) in the intervention counties, and asphyxia-related deaths in the delivery room decreased from 27.6 to 5.0 per 100,000 (P=0.076). There was no difference over time in asphyxia rates for the control counties. CONCLUSIONS: The intervention has not only improved skills of health providers, decreased the mortality and morbidity of birth asphyxia, but also resulted in effective implementation of guidelines and protocols within hospitals.