Determinants of low birth weight among newborns delivered in China: a prospective nested case-control study in a mother and infant cohort.

This nested case-control study aimed to investigate the determinants of low birth weight among newborn babies delivered in Shenzhen, Guangdong, China. We recorded socio-demographic data, health status before pregnancy, pregnancy outcomes and complications in a Shenzhen mother and infant cohort. Among 8951 cases, 401 (4.48%) had low birth weight and 1.65% were full-term with LBW. Maternal body mass index, family income, history of pregnancy, hypertension before pregnancy, vaginal bleeding in 1st trimester, pregnancy-related diabetes, hypertension, placenta previa, placental abruption, premature rupture of membrane, oligohydramnios, and placental types were significantly associated with low birth weight (P < 0.05). In this study, high-risk and mainly preventable factors were linked to low birth weight. Adequate antenatal care, proper maternal nutrition and implementation of proven strategies to prevent high-risk factors may be effective ways to reduce the incidence of low birth weight.

What is already known on this subject? Low birth weight (LBW) is associated with adverse perinatal outcomes and neonatal disease and death. The aim of this study was to investigate the factors affecting low birth weight infants in a developed region in China.What the results of this study add? According to this study, the incidence of LBW in Shenzhen of China was 4.48%. Maternal body mass index, family income, history of pregnancy, hypertension before pregnancy, vaginal bleeding in 1st trimester, pregnancy-related diabetes, hypertension, placenta previa, placental abruption, premature rupture of membrane, oligohydramnios, and placental types were significantly associated with LBW.What the implications are of these findings for clinical practice and/or further research? This study suggests that good prenatal care, maternal nutrition and implementation of proven strategies to manage high-risk factors are needed to prevent and reduce the incidence of LBW. Health care providers could use our findings to identify good antenatal care and provide individualised interventions targeting women with risk factors.

Circular RNA hsa-circ-0005238 enhances trophoblast migration, invasion and suppresses apoptosis via the miR-370-3p/CDC25B axis.

Background: Fetal growth restriction (FGR) is attributed to various maternal, fetal, and placental factors. Trophoblasts participate in the establishment and maintenance of pregnancy from implantation and placentation to providing nutrition to fetus. Studies have reported that impaired trophoblast invasion and proliferation are among factors driving development of FGR. Circular RNAs (circRNAs) can regulate trophoblast function. We assessed the significance of circRNAs underlying FGR development. Materials and methods: Next generation sequencing (NGS) was carried out to quantify levels of circRNAs in placenta tissues with and without FGR. In vitro experiments including transfection, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) assays, flow cytometry analyses, Transwell assays, wound healing assays, western blotting, qRT-PCR, dual-luciferase assays, immunofluorescence staining, and RIP assay were performed. Results: There were 18 differentially expressed circRNAs between FGR placentas and uncomplicated pregnancies, while levels of hsa-circ-0005238 were markedly low in FGR placentas. Our in vitro experiments further revealed that hsa-circ-0005238 suppressed apoptosis and enhanced proliferation, migration, invasion of trophoblast cell lines. The hsa-miR-370-3p was identified as a direct target of hsa-circ-0005238. Mechanistically, hsa-miR-370-3p prevents invasion as well as migration of trophoblast cells by downregulating CDC25B. Conclusion: The hsa-circ-0005238 modulates FGR pathogenesis by inhibiting trophoblast cell invasion and migration through sponging hsa-miR-370-3p. Hence, targeting this circRNA may be an attractive strategy for FGR treatment.

A specific identification platform based on biscuit-like bismuth nanosheets for label-free electrochemical immunosensor.

A label-free electrochemical immunosensor based on the biscuit-like bismuth nanosheets (BiNSs) and multi-wall carbon nanotubes-chitosan-gold nanoparticles (MWCNTs-Chit-AuNPs) was constructed for the detection of human immunoglobulin G (hIgG). The biscuit-like BiNSs prepared by one-step aqueous phase reduction method had a large electroactive surface area, 1.7 times that of bare glassy carbon electrode (GCE), which could load more antibodies and were used as a larger platform for the specific identification of antigens and antibodies. In addition, MWCNTs and AuNPs with good conductivity could be used to regulate the sensing interface, which promoted electron transfer greatly. Moreover, the AuNPs could stably anchor anti-hIgG by the affinity interaction between amine group of antibody and AuNPs, which greatly increased the number of anti-hIgG attached to the sensing platform. Under the optimal conditions, the proposed immunosensor exhibited excellent analytical performance for hIgG with a wide linear response of 0.01-1000 ng/mL and a low detection limit of 4.26 pg/mL. The electrochemical immunosensor exhibited favorable reproducibility, excellent specificity and high storage stability. Additionally, the immunosensor could be applied to determining hIgG in human serum samples as well. Considering these advantages, the electrochemical immunosensor has the potential application in clinical diagnosis.

Reliability and validity of the Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) in Chinese people.

OBJECTIVE: To investigate the reliability and validity of Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) for different population cohorts in the city of Guangzhou, Guangdong, China and to provide evidence and tools for further evaluation of healthy fitness of Chinese population and related factors. DESIGN: Cross-sectional study. SETTING: Urban neighbourhood and Medical University. PARTICIPANTS: Elderly people (n=393; mean age 68.27±6.38 years; 53.18% male), university students (n=390; mean age 19.29±1.29 years; 38.21% male) and urban residents (n=393; mean age 32.23±9.41 years; 44.78% male). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were evaluated the reliability and validity of HFMS V1.0 by internal consistency evaluation, split-half reliability, test-retest reliability, convergent and discriminant construct validity, and factor analysis. RESULTS: The Cronbach's α coefficients for HFMS V1.0 were all greater than 0.85 for overall scale of total samples and three individual groups, and the split-half reliability and intragroup correlation coefficients were both greater than 0.70 (p<0.01). The correlation of each item, dimension and subscales ranged from 0.52 to 0.91 (p < 0.01). A total of 10 factors were screened by exploratory factor analysis with the cumulative contribution rate of 61.40%, basically consistent with the theoretical structure of scale. The confirmatory factor analysis indicated good fit: CMIN/DF=3.45, root mean square error of approximation=0.05, GFI=0.91, AGFI=0.90, IFI=0.90, comparative fit index=0.90. CONCLUSION: HFMS V1.0 showed acceptable reliability and validity in the test of healthy fitness of general population in Guangzhou. This scale could be a reliable measurement tool for evaluation of healthy fitness and potential risk factors.

Associations of environment and lifestyle factors with suboptimal health status: a population-based cross-sectional study in urban China.

INTRODUCTION: Suboptimal health status (SHS), an intermediate state between chronic disease and health, is characterized by chronic fatigue, non-specific pain, headaches, dizziness, anxiety, depression, and functional system disorders with a high prevalence worldwide. Although some lifestyle factors (e.g. smoking, alcohol consumption, physical exercise) and environmental factors (e.g. air quality, noise, living conditions) have already been studied, few studies can comprehensively illustrate the associations of lifestyle and environment factors with general, physical, mental, and social SHS. METHODS: A cross-sectional study was conducted among 6750 urban residents aged 14 years or over in five random cities from September 2017 to September 2018 through face-to-face questionnaires. There were 5881 valid questionnaires with a response rate of 87%. A general linear model and structural equation model were developed to quantify the effects of lifestyle behaviors and environment factors on SHS. RESULTS: The detection rates of general, physical, mental, and social SHS were 66.7, 67.0, 65.5, and 70.0%, respectively. Good lifestyle behaviors and favorable environment factors positively affected SHS (P < 0.001). Lifestyle behaviors had the largest effect on physical SHS (ß = - 0.418), but the least on social SHS (ß = - 0.274). Environment factors had the largest effect on mental SHS (ß = 0.286), but the least on physical SHS (ß = 0.225). CONCLUSIONS: Lifestyle behaviors and environment factors were important influencing factors of SHS. Physical SHS was more associated with lifestyle. Lifestyle and environment were similarly associated with mental and social SHS.

Reliability and validity of Healthy Fitness Measurement Scale Version1.0 (HFMS V1.0) in Chinese elderly people.

PURPOSE: We examined the reliability and validity of the Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) specifically on elderly people in China. METHODS: We carried out a cross-sectional study in December 2020 and enrolled 800 elderly people through stratified sampling technique, including 777 valid samples (with a mean age of 71.81 ± 8.36 years), of which 382 cases (49.2%) were women. The level of healthy fitness was measured using the HFMS V1.0. The Cronbach's alpha coefficient, split-half reliability, test-retest reliability, convergent and discriminant validity, exploratory factor and confirmatory factor were calculated for assessing the reliability and validity of HFMS V1.0. RESULTS: HFMS V1.0 consists of 8 dimensions and 38 items. The scale had acceptable reliability (Cronbach's alpha = 0.920, split-half = 0.946, test-retest = 0.878). Exploratory factor analysis showed KMO value =0.927, and uncovered 10 factors with the cumulative contribution rate of 65.71% and all factor loads over 0.40. The item distribution was consistent with the initial expectation of the scale. The confirmatory factor analysis indicated good fit: CMIN/DF = 2.796, RMSEA = 0.048, IFI =0.914, TLI = 0.902, CFI = 0.913. CONCLUSION: HFMS V1.0 was shown to have acceptable reliability and validity indices for this sample. Collectively, HFMS V1.0 is reliable and efficient to measure the healthy fitness of elderly people. It is recommended to use it among the elderly in other Chinese cities in the future to ensure uniformity and objectivity. This scale can be carried out to evaluate of the effectiveness of public health measures in improving the healthy fitness level of the elderly and optimizing public health policies.

Association analysis of Suboptimal health Status: a cross-sectional study in China.

BACKGROUND: Suboptimal health status (SHS) among urban residents is commonplace in China. However, factors influencing SHS have not been thoroughly explored, especially with regard to the effects of internal factors (e.g., personality and health awareness) on SHS. METHODS: A cross-sectional study was conducted with a nationally representative sample of 5460 Chinese urban residents..SHS was measured using the Suboptimal Health Mesurement Scale Version 1.0. Demographic information, and information pertaining to lifestyle behaviors, environmental factors, and internal factors were abtained through a questionnaire. The associations between demographic information, lifestyle behaviors, environmental factors, internal factors and SHS were assessed using logistic regression. RESULTS: Of the 5460 participants (with a mean age of 41.56 ±  16.14 years), 2640 (48.4 %) were men. Out of 36 variables, 23 were significantly associated with SHS: age (odds ratio [OR]: 1.014), an education level of high school/junior college (OR: 1.443) , marital status (OR: 1.899), area of registered permanent residence (OR: 0.767), monthly household income (p < 0.001) , exposure to second-hand smoke (p = 0.001), alcohol drinking (OR: 1.284), bad eating habits (OR: 1.717), not sleeping before 11 p.m. every day (p = 0.002), spending time online more than five hours a day (OR: 1.526), having a good relationship with parents during one's growth period (OR: 0.602), living with good quality air (OR:0.817), living in not crowded conditions (OR:0.636), having a harmonious neighborhood (OR:0.775), having adequate fitness facilities (OR:0.783), one's health being affected by two-child policy (OR: 1.468) and medical policies (OR: 1.265) , high adverse quotient (OR: 0.488), many (≥3 kinds) interests and hobbies (OR: 0.617), mature and steady personality traits (OR: 0.469) , a high attention to one's health (OR: 0.833), and effective health promotion induced by leading a leisurely lifestyle (OR: 0.466) were significantly associated with SHS. CONCLUSIONS: All these variables were included demographic information, lifestyle behaviors, environmental factors and internal factors. Our study supports the benefits of controlling both internal and external factors in preventing suboptimal health.

Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8+ T cell immune response and antitumor effects in a preclinical cervical cancer model.

BACKGROUND: Bortezomib, a proteasome inhibitor and suberoylanilide hydroxamic acid (SAHA, also known as Vorinostat), a histone deacetylase inhibitor, have been recognized as potent chemotherapeutic drugs. Bortezomib and SAHA are FDA-approved for the treatment of cutaneous T cell lymphoma and multiple myeloma/mantle cell lymphoma, respectively. Furthermore, the combination of the bortezomib and SAHA has been tested in a variety of preclinical models and in clinical trials and may be ideal for the treatment of cancer. However, it remains unclear how this treatment strategy affects the host immune response against tumors. RESULTS: Here, we used a well-defined E6/E7-expressing tumor model to examine how the immune system can be motivated to act against tumor cells expressing tumor antigens. We demonstrate that the combination of bortezomib and SAHA elicits potent antitumor effects in TC-1 tumor-bearing mice. Additionally, we are the first to show that treatment with bortezomib and SAHA leads to tumor-specific immunity by rendering tumor cells more susceptible to killing by antigen-specific CD8+ T cells than treatment with either drug alone. CONCLUSIONS: The current study serves an important foundation for the future clinical application of both drugs for the treatment of cervical cancer.

Histone deacetylase inhibitor AR-42 enhances E7-specific CD8⁺ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination.

UNLABELLED: We have previously created a potent DNA vaccine encoding calreticulin linked to the human papillomavirus (HPV) oncogenic protein E7 (CRT/E7). While treatment with the CRT/E7 DNA vaccine generates significant tumor-specific immune responses in vaccinated mice, the potency with the DNA vaccine could potentially be improved by co-administration of a histone deacetylase inhibitor (HDACi) as HDACi has been shown to increase the expression of MHC class I and II molecules. Thus, we aimed to determine whether co-administration of a novel HDACi, AR-42, with therapeutic HPV DNA vaccines could improve the activation of HPV antigen-specific CD8(+) T cells, resulting in potent therapeutic antitumor effects. To do so, HPV-16 E7-expressing murine TC-1 tumor-bearing mice were treated orally with AR-42 and/or CRT/E7 DNA vaccine via gene gun. Mice were monitored for E7-specific CD8(+) T cell immune responses and antitumor effects. TC-1 tumor-bearing mice treated with AR-42 and CRT/E7 DNA vaccine experienced longer survival, decreased tumor growth, and enhanced E7-specific immune response compared to mice treated with AR-42 or CRT/E7 DNA vaccine alone. Additionally, treatment of TC-1 cells with AR-42 increased the surface expression of MHC class I molecules and increased the susceptibility of tumor cells to the cytotoxicity of E7-specific T cells. This study indicates the ability of AR-42 to significantly enhance the potency of the CRT/E7 DNA vaccine by improving tumor-specific immune responses and antitumor effects. Both AR-42 and CRT/E7 DNA vaccines have been used in independent clinical trials; the current study serves as foundation for future clinical trials combining both treatments in cervical cancer therapy. KEY MESSAGE: AR-42, a novel HDAC inhibitor, enhances potency of therapeutic HPV DNA vaccines AR-42 treatment leads to strong E7-specific CD8+ T cell immune responses AR-42 improves tumor-specific immunity and antitumor effects elicited by HPV DNA vaccine AR-42 is more potent than clinically available HDACi in combination with HPV DNA vaccine.

Intratumoral injection of therapeutic HPV vaccinia vaccine following cisplatin enhances HPV-specific antitumor effects.

Despite the conventional treatments of radiation therapy and chemotherapy, the 5-year survival rates for patients with advanced-stage cervical cancers remain low. Cancer immunotherapy has emerged as an alternative, innovative therapy that may improve survival. Here, we utilize a preclinical HPV-16 E6/E7-expressing tumor model, TC-1, and employ the chemotherapeutic agent cisplatin to generate an accumulation of CD11c+ dendritic cells in tumor loci making it an ideal location for the administration of therapeutic vaccines. Following cisplatin treatment, we tested different routes of administration of a therapeutic HPV vaccinia vaccine encoding HPV-16 E7 antigen (CRT/E7-VV). We found that TC-1 tumor-bearing C57BL/6 mice treated with cisplatin and intratumoral injection of CRT/E7-VV significantly increased E7-specific CD8+ T cells in the blood and generated potent local and systemic antitumor immune responses compared to mice receiving cisplatin and CRT/E7-VV intraperitoneally or mice treated with cisplatin alone. We further extended our study using a clinical grade recombinant vaccinia vaccine encoding HPV-16/18 E6/E7 antigens (TA-HPV). We found that intratumoral injection with TA-HPV following cisplatin treatment also led to increased E7-specific CD8+ T cells in the blood as well as significantly decreased tumor size compared to intratumoral injection with wild type vaccinia virus. Our study has strong implications for future clinical translation using intratumoral injection of TA-HPV in conjunction with the current treatment strategies for patients with advanced cervical cancer.