Activated STING1 rides the Rafeesome.

Over the past decade, accumulated studies have reported the presence of non-canonical macroautophagy/autophagy characterized by the shared usage of the autophagy machinery and distinct components that function in multiple scenarios but do not involve lysosomal degradation. One type of non-canonical autophagy is secretory autophagy, which facilitates the secretion of various cargoes. In a recent work from Gao et al. the ER-membrane protein STING1 has been identified as a novel substrate of secretory autophagy. The secretion of activated STING1 is mediated by its packing into the rafeesome, a newly identified organelle formed upon the fusion of RAB22A-mediated non-canonical autophagosome with an early endosome. Moreover, extracellular vesicles containing activated STING1 induce antitumor immunity in recipient cells, a process potentially promoted by RAB22A.

Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis.

CONTEXT: Ferulic acid (FA) has antioxidative and anti-inflammatory effects, and is a promising drug to treat sepsis. OBJECTIVE: To study the therapeutic effect of FA in sepsis-induced acute lung injury (ALI) and its underlying mechanisms. MATERIALS AND METHODS: The caecal ligation and puncture (CLP) manoeuvre was applied to establish a murine model of sepsis-induced ALI, and female BALB/c mice (6 mice per group) were subjected to 100 mg/kg FA or 0.8 mg/kg ferrostatin-1 (Fer-1, ferroptosis inhibitor) treatment to clarify the role of FA in preserving alveolar epithelial barrier function and inhibiting ferroptosis. Lipopolysaccharide (LPS; 500 ng/mL)-induced cell models were prepared and subjected to FA (0.1 µM), sh-Nrf2, and Fe (Fe-citrate, ferroptosis inducer; 5 M) treatment to study the in vitro effect of FA on LPS-induced alveolar epithelial cell injury and the role of the Nrf2/HO-1 pathway. RESULTS: We found that FA decreased the lung injury score (48% reduction), lung wet/dry weight ratio (33% reduction), and myeloperoxidase activity (58% reduction) in sepsis-induced ALI. Moreover, FA inhibited ferroptosis of alveolar epithelial cells and improved alveolar epithelial barrier dysfunction. The protective role of FA against alveolar epithelial barrier dysfunction could be reversed by the ferroptosis inducer Fe-citrate, suggesting that FA alleviates alveolar epithelial barrier dysfunction by inhibiting ferroptosis. Mechanistically, we found that FA inhibited ferroptosis of alveolar epithelial cells by activating the Nrf2/HO-1 pathway. CONCLUSION: Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment.

Immunogenicity and safety of BNT162b2 mRNA vaccine in Chinese adults: A phase 2 randomised clinical trial.

Background: BNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited. Methods: This phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18-85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 µg or placebo, administered 21 days apart. Study participants, study personnel, investigators, statisticians, and the sponsor's study management team were blinded to treatment assignment. Primary immunogenicity endpoints were the geometric mean titers (GMTs) of neutralising antibodies to live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seroconversion rates (SCR) 1 month after the second dose. Safety assessments included reactogenicity within 14 days of vaccination, adverse events (AEs), and clinical laboratory parameters. Randomised participants who received at least one dose were included in the efficacy and safety analyses on a complete case basis (incomplete/missing data not imputed). Results up to 6 months after the second dose are reported. Findings: Overall, 959 participants (all of Han ethnicity) who were recruited between December 5th, 2020 and January 9th, 2021 received at least one injection (BNT162b2, n=720; placebo, n=239). At 1 month after the second dose, the 50% neutralising antibody GMT was 294.4 (95% CI; 281.1-308.4) in the BNT162b2 group and 5.0 (95% CI; 5.0-5.0) in the placebo group. SCRs were 99.7% (95% CI; 99.0%-100.0%) and 0% (95% CI; 0.0%-1.5%), respectively (p<0.0001 vs placebo). Although the GMT of neutralising antibodies in the BNT162b2 group was greatly reduced at 6 months after the second dose, the SCR still remained at 58.8%. BNT162b2-elicited sera neutralised SARS-CoV-2 variants of concern. T-cell responses were detected in 58/73 (79.5%) BNT162b2 recipients. Reactogenicity was mild or moderate in severity and resolved within a few days after onset. Unsolicited AEs were uncommon at 1 month following vaccine administration, and there were no vaccine-related serious AEs at 1 month or 6 months after the second dose. Interpretation: BNT162b2 vaccination induced a robust immune response with acceptable tolerability in Han Chinese adults. However, follow-up duration was relatively short and COVID-19 rates were not assessed. Safety data collection is continuing until 12 months after the second dose. Funding: BioNTech - sponsored the trial. Shanghai Fosun Pharmaceutical Development Inc. (Fosun Pharma) - conducted the trial, funded medical writing. ClinicalTrialsgov registration number: NCT04649021. Trial status: Completed.

Generation of singlet oxygen over CeO2/K,Na-codoped g-C3N4 for tetracycline hydrochloride degradation over a wide pH range.

Singlet oxygen (1O2) species have been widely studied in catalytic oxidation and photodynamic therapy (PDT) and so on due to their unique properties, such as their long lifetime, wide pH tolerance, relative long migration distance, and high selectivity. In this work, 1O2 could be generated over CeO2/K,Na-codoped g-C3N4 heterojunction (CeO2/CN) fabricated using a molten salt method in the presence of H2O2 in dark for the first time, which was used as a Fenton-like catalyst to degrade the emerging tetracycline hydrochloride (TCH) pollutant through a Fenton-like reaction. A significantly-enhanced catalytic activity was observed over CeO2/CN compared with g-C3N4 and commercial CeO2. The Ce4+/Ce3+ redox system was found to play a vital role in the formation of 1O2 from the disproportionation of superoxide radical (˙O2-). The 1O2 and ˙O2- radicals were observed as the main active species in the highly-efficient degradation of TCH over a wide pH range (1.20-11.20). The strong interfacial interaction of CeO2/CN promoted the Ce4+/Ce3+ redox and the generation of active species. The catalytic mechanism of TCH decomposition was also proposed. This finding introduces an efficient and promising approach for the preparation of the highly-effective Fenton-like catalysts for water purification.

Immune Persistence and Safety After SARS-CoV-2 BNT162b1 mRNA Vaccination in Chinese Adults: A Randomized, Placebo-Controlled, Double-Blind Phase 1 Trial.

INTRODUCTION: BNT162b1 is a lipid nanoparticle-formulated, nucleoside-modified mRNA SARS-CoV-2 vaccine. Here, we report safety and immune persistence data following a primary two-dose vaccination schedule administered 21 days apart. METHODS: Immune persistence was determined at month 3 in 72 younger participants (aged 18-55 years) and at month 6 in 70 younger and 69 older participants (aged 65-85 years). RESULTS: In younger participants, neutralizing antibody (nAb) geometric mean titers (GMTs) for the 10 and 30 µg dose levels declined from 233 and 254 (21 days after dose 2) to 55 and 87 at month 3, respectively, and to 16 and 27 at month 6, respectively. In older participants, nAb GMTs declined from 80 and 160 (21 days after dose 2) to 10 and 21 at month 6. Overall, higher antibody titers were observed in younger participants, and the 30 µg dose induced higher levels of nAb, which declined more slowly by month 6. No serious adverse events were reported in the vaccine group. CONCLUSION: This study showed BNT162b1 maintains a favorable safety profile in younger and older participants in the 6 months after vaccination. This study further extends our understanding of immune persistence and the safety of the BNT162b1 vaccine as a candidate vaccine in the BioNTech pipeline. TRIAL REGISTRATION NUMBER: NCT04523571, registered August 21, 2020.

Loss of MBD2 ameliorates LPS-induced alveolar epithelial cell apoptosis and ALI in mice via modulating intracellular zinc homeostasis.

Apoptosis of alveolar epithelial cells is a critical initial link in the pathogenesis of acute lung injury (ALI), recent studies have revealed that Methyl-CpG binding domain protein 2 (MBD2) was involved in the execution of apoptosis, yet its role in ALI remained unclear. In the present study, we aim to explore the role and mechanism of MBD2 in the pathogenesis of ALI. We have found that MBD2 expression, in parallel to apoptosis, increased in alveolar epithelial cells of mice treated with LPS, knockout of MBD2 reduced apoptosis and protected mice from LPS-induced ALI. In MLE-12 cells, a cell line of murine alveolar epithelial cells, LPS induced MBD2 expression and apoptosis in a dose- and time-dependent manner. Knockdown of MBD2 with shRNA alleviated, while overexpression of MBD2 increased LPS-induced apoptosis. Mechanistically, intracellular zinc level decreased when MLE-12 cells were treated with LPS. MBD2 knockdown restored intracellular zinc level after LPS treatment, and MBD2 overexpression further aggravated LPS-induced intracellular zinc loss. Metal transcription factor 1 (MTF1) is a critical transcription factor in charge of intracellular zinc efflux. LPS treatment induced MTF1 expression both in vivo and in vitro. Inhibition of MTF1 reduced LPS-induced apoptosis in MLE-12 cells. MBD2 could bind to the promoter region of MTF1 and promote MTF1 expression. Collectively, these data indicated that loss of MBD2-ameliorated LPS-induced alveolar epithelial cell apoptosis and ALI in mice via modulating intracellular zinc homeostasis by upregulating MTF1.

Development and validation of a novel blending machine learning model for hospital mortality prediction in ICU patients with Sepsis.

BACKGROUND: Early prediction of hospital mortality is crucial for ICU patients with sepsis. This study aimed to develop a novel blending machine learning (ML) model for hospital mortality prediction in ICU patients with sepsis. METHODS: Two ICU databases were employed: eICU Collaborative Research Database (eICU-CRD) and Medical Information Mart for Intensive Care III (MIMIC-III). All adult patients who fulfilled Sepsis-3 criteria were identified. Samples from eICU-CRD constituted training set and samples from MIMIC-III constituted test set. Stepwise logistic regression model was used for predictor selection. Blending ML model which integrated nine sorts of basic ML models was developed for hospital mortality prediction in ICU patients with sepsis. Model performance was evaluated by various measures related to discrimination or calibration. RESULTS: Twelve thousand five hundred fifty-eight patients from eICU-CRD were included as the training set, and 12,095 patients from MIMIC-III were included as the test set. Both the training set and the test set showed a hospital mortality of 17.9%. Maximum and minimum lactate, maximum and minimum albumin, minimum PaO2/FiO2 and age were important predictors identified by both random forest and extreme gradient boosting algorithm. Blending ML models based on corresponding set of predictors presented better discrimination than SAPS II (AUROC, 0.806 vs. 0.771; AUPRC 0.515 vs. 0.429) and SOFA (AUROC, 0.742 vs. 0.706; AUPRC 0.428 vs. 0.381) on the test set. In addition, calibration curves showed that blending ML models had better calibration than SAPS II. CONCLUSIONS: The blending ML model is capable of integrating different sorts of basic ML models efficiently, and outperforms conventional severity scores in predicting hospital mortality among septic patients in ICU.

Standardized treatment and determinants on 9,059 syphilis-infected pregnant women during 2015-2018 in Hunan, China.

This study was aimed to describe the standardized treatment rate of syphilis-infected pregnant women in Hunan province and to explore the determinants for standardized treatment. All syphilis-infected pregnant women registered in the Information System of Prevention of Mother-to-Child Transmission of Syphilis Management (IPMTCT) in Hunan between January 2015 and December 2018 were included in this study. Among 9,059 pregnant women with syphilis, 7,797 received syphilis treatment, with a treatment rate of 86.1%, and 4,963 underwent standardized syphilis treatment, with an average standardized treatment rate of 54.8%. The facilitators for the standardized treatment included abnormal reproductive histories (aOR = 1.15, 95%CI:1.03-1.28), time of first prenatal care within 1-12 weeks (aOR = 5.17, 95%CI:4.19-6.37) or within 13-27 weeks (aOR = 5.56, 95%CI:4.46-6.92), previous syphilis infection (aOR = 1.64, 95%CI: 1.48-1.81), and definite syphilis infection status of sexual partner (negative: aOR = 1.73, 95%CI:1.57-1.91; positive: aOR = 1.62, 95%CI:1.34-1.95). The barriers included marital status being unmarried/divorced/widowed (aOR = 0.81, 95%CI: 0.65-0.99), pluripara (aOR = 0.58, 95%CI: 0.46-0.74), number of children ≥ 2 (aOR = 0.45, 95%CI: 0.35-0.57), and syphilis clinical stage being primary/secondary/tertiary (aOR = 0.72, 95%CI: 0.58-0.88) or unclear (aOR = 0.78, 95%CI: 0.70-0.86). Though the treatment rate of syphilis-infected pregnant women was high, the standardized treatment rate was low. The facilitators and barriers on standardized treatment of gestational syphilis were identified at the patient level.

Anemia prevalence, severity and associated factors among children aged 6-71 months in rural Hunan Province, China: a community-based cross-sectional study.

BACKGROUND: In recent 10 years, with the rapid socioeconomic development and the extensive implementation of children nutrition improvement projects, the previous epidemiological data cannot reflect the actual level of anemia among children in China, especially in rural areas. Therefore, this study analyzed the prevalence, severity and associated factors of anemia among children aged 6-71 months in rural Hunan Province. METHODS: A community-based cross-sectional study was conducted. Through multistage stratified cluster sampling, 5229 children aged 6 to 71 months and their caregivers were randomly selected from 72 villages across 24 towns in 12 counties from rural Hunan. The demographic characteristics of children and their caregivers, feeding practice, nutritional status of children, caregivers' anemia-related feeding knowledge, and gestational conditions of mothers were acquired by using a unified questionnaire. Peripheral blood from the left-hand middle fingertip was sampled from each child, and hemoglobin concentration was measured using a HemoCue301 portable hemoglobin analyzer (Sweden). Associated factors analyses involving overall anemia and anemia severities were conducted on multivariate logistic regression models. RESULTS: The overall anemia prevalence was 8.8%, and the prevalence of mild, moderate and severe anemia was 6.3, 2.5 and 0.1%, respectively. Children age groups of 6-11 months, 12-23 months and 36-47 months, exclusive breast-feeding within 6 months after birth, and maternal moderate/severe anemia were significantly associated with an increased risk of overall anemia in children. Children age groups of 6-11 months and 12-23 months were significantly associated with an increased risk of mild anemia in children. Children age groups of 6-11 months, 12-23 months and 36-47 months, low caregivers' anemia-related feeding knowledge level, and maternal moderate/severe anemia were significantly associated with an increased risk of moderate/severe anemia in children. Children who underwent regular physical examination were less likely to have moderate/severe anemia. The common protective factor for overall, mild and moderate/severe anemia in children was high family income. CONCLUSIONS: The anemia status of preschool children in rural Hunan Province was a mild public health problem and associated with children age group, feeding practice, regular physical examination, family income, caregivers' anemia-related feeding knowledge level, and maternal moderate/severe anemia.

Preparation of multi-dimensional (1D/2D/3D) carbon/g-C3N4 composite photocatalyst with enhanced visible-light catalytic performance.

A multi-dimensional (1D/2D/3D) carbon/g-C3N4 composite photocatalyst (CCN) was successfully prepared by a facile method with carbon from cheap absorbent cotton wool. The activities and stabilities of CCN were evaluated by photo-degrading Rhodamine B (RhB) under visible light irradiation. The effect of carbon content in composite on the catalytic activities was investigated. The results show that a good interfacial contact can be observed between g-C3N4 and carbon materials in CCN. It reveals an enhanced photocatalytic activity in photocatalytic decomposition of RhB compared with g-C3N4. The carbon content has obvious effect on the performance of CCN, and the optimal carbon content in CCN is 1 wt% (CCN1.0). The first-order rate constant (k) of CCN1.0 is approximately 5.5 and 3.4 times those of g-C3N4 and AC1.0/g-C3N4. The CCN1.0 catalyst also shows the excellent photocatalytic stability in the recycling experiments. The enhanced catalytic performance of CCN is mainly due to an increase in electron-hole pair separation efficiency and visible light adsorption after coupling carbon. The hole and •O2- radicals are the main active species, and •O2- plays a more important role than h+. The photocatalytic mechanism over CCN1.0 was proposed. This work will provide a new insight to prepare highly-efficient g-C3N4-based photocatalysts.

Maternal HIV infection and risk of adverse pregnancy outcomes in Hunan province, China: A prospective cohort study.

This study described the prevalence of adverse pregnancy outcomes (APOs) in Chinese HIV-infected pregnant women, and examined the relationship between maternal HIV infection /HIV-related factors and APOs.This prospective cohort study was carried out among 483 HIV-infected pregnant women and 966 HIV-uninfected pregnant women. The HIV-infected and HIV-uninfected women were enrolled from midwifery hospitals in Hunan province between October 2014 and September 2017. All data were extracted in a standard structured form, including maternal characteristics, HIV infection status, HIV-related factors and their pregnancy outcomes. APOs were assessed by maternal HIV infection status and HIV-related factors using logistic regression analysis.The incidences of stillbirth (3.9% vs 1.1%), preterm birth (PTB) (8.9% vs 3.7%), low birth weight (LBW) (12.2% vs 3.1%) and small for gestational age (SGA) (21.3% vs 7.0%) were higher in HIV-infected women than HIV-uninfected women, with adjusted ORs of 2.77 (95%CI: 1.24-6.17), 2.37 (95%CI: 1.44-3.89), 4.20 (95%CI: 2.59-6.82) and 3.26 (95%CI: 3.26-4.64), respectively. No differences were found in neonatal asphyxia or birth defects between HIV-infected and HIV-uninfected groups, with adjusted ORs of 1.12 (95%CI: 0.37-3.43) and 1.10 (95%CI: 0.51-2.39), respectively. Among HIV-infected pregnant women, different antiretroviral (ARV) regimens were significantly associated with stillbirths, but not PTB, LBW or SGA. Compared with untreated HIV infection (10.1%), both mono/dual therapy and HAART were associated with a reduced risk of stillbirths (2.0% and 3.2%, respectively), with an AOR of 0.19 (95%CI: 0.04-0.92) and 0.31 (95%CI: 0.11-0.85), respectively. Initial time of ARV drugs use and HIV infection status of the sexual partner were not associated with maternal APOs.The findings of this study indicated that maternal HIV infection was associated with significantly increased risks of stillbirth, PTB, LBW and SGA, but not neonatal asphyxia or birth defects. On the condition that most HIV-infected pregnant women started ARV therapy in or after the second trimester, both mono/dual therapy and HAART had a protective effect on stillbirth compared with untreated HIV infection. As some important confounders were not effectively controlled and the specific regimens of HAART were not analyzed, the above findings may have certain bias.

Alanylglutamine Relieved Asthma Symptoms by Regulating Gut Microbiota and the Derived Metabolites in Mice.

OBJECTIVE: Allergic asthma is a chronic inflammatory disease, which seriously affects the life quality of patients, especially children. Alanylglutamine is a nutritional supplement with potential protective and anti-inflammatory effects, but its function in allergic asthma remains elusive. In this study, we focused on the investigations of the roles and functional mechanism of Alanylglutamine in asthma. METHODS: Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. 16S rDNA sequencing was performed to compare the diversity of intestinal microorganisms under different treatments. Gas chromatography was utilized to screen the intestinal microbe-short-chain fatty acids in the stool. The lung tissue was extracted to determine signaling pathways, including AMPK, NF-κB, mTOR, STAT3, IKKß, TGF-ß, and IL-1ß through Western blot or RT-qPCR. RESULTS: It was observed that Alanylglutamine reduced the cytokine in OVA-induced allergic asthma mice. H&E staining showed obvious pneumonia symptoms in the asthma group, while Alanylglutamine alleviated the inflammatory infiltration. Alanylglutamine reversed gut microbiota compositions in OVA-induced allergic asthma mice and enhanced the butyric acid level. The protective role of Alanylglutamine may be associated with the gut microbiota-butyric acid-GPR43 pathway in asthma mice. In contrast to the OVA group, Alanylglutamine activated the protein expression of P-AMPK/AMPK and inhibited the protein expression of P-mTOR/mTOR, P-P65/P65, P-STAT3/STAT3, P-IKKß/IKKß, TGF-ß, and IL-1ß, with similar effects from butyric acid. CONCLUSION: The results indicated that Alanylglutamine might be beneficial for asthma, and its effect was achieved through the regulation on microbiota and the derived metabolites. The therapeutic effects might be associated with AMPK, NF-κB, mTOR, and STAT3 signaling pathways. These findings will help identify effective therapeutic direction to alleviate allergic inflammation of the lungs and airways.

Maternal cosmetics use during pregnancy and risks of adverse outcomes: a prospective cohort study.

To probe into the associations between maternal personal cosmetics use during pregnancy and risk of adverse outcomes, and explore the potential dose-response relationships, we carried out a prospective cohort study involving 9710 pregnant women in Zhuzhou City and Xiangtan City in Hunan province during 2016-2017. A structured questionnaire was used to collection information for the pregnant women and their pregnancy outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by binary or multinomial logistic regressions. The study population included 4652 (47.9%) cosmetics non-users and 5058 (52.1%) cosmetics users. Cosmetics use was associated with an increased risk of small for gestational age (SGA) (aOR = 1.23, 95%CI 1.04 to 1.44), compared with cosmetics non-users. A positive dose-response relationship between frequency of cosmetics use and SGA was observed, although a borderline association was found at low use frequency (1-2 times per week; aOR = 1.18, 95%CI 0.99 to 1.40) and moderate use frequency (3-4 times per week; aOR = 1.23, 95%CI 0.92 to 1.64). High-frequency of cosmetics use (≥5 times per week) was significantly correlated with a higher risk of SGA (aOR = 1.83, 95%CI 1.25 to 2.69). No significant association between personal cosmetics use and the risk of preterm birth, low birth weight, macrosomia, or large for gestational age was observed. The present study suggests that personal cosmetics use will increase the risk of SGA, but further research is required to determine which cosmetic products may account for the higher risk of SGA.

mTORC1-Rps15 Axis Contributes to the Mechanisms Underlying Global Translation Reduction During Senescence of Mouse Embryonic Fibroblasts.

The reduction of protein translation is a common feature in senescent cells and aging organisms, yet the underlying mechanisms are not fully understood. Here we show that both global mRNA translation and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) kinase activity are declined in a senescent model of mouse embryonic fibroblasts (MEFs). Furthermore, RNA-seq analyses from polysomal versus total mRNA fractions identify TOP-like mRNA of Rps15 whose translation is regulated by mTORC1 during MEF senescence. Overexpression of Rps15 delays MEF senescence, possibly through regulating ribosome maturation. Together, these findings indicate that the activation of mTORC1-Rps15 axis ameliorate senescence by regulating ribosome biogenesis, which may provide further insights into aging research.

Xuebijing combined with ulinastation benefits patients with sepsis: A meta-analysis.

BACKGROUND: The potential benefits and possible risks associated with Xuebijing when combined with ulinastatin for sepsis treatment are not fully understood. METHODS: Databases, such as PubMed, Web of Science, CNKI, WanFang and VIP, were searched to collect randomized, controlled trials. Studies were screened, data were extracted, and the methodological quality was assessed by two reviewers independently. A meta-analysis was carried out with Stata 11.0 software. RESULTS: A total of 16 studies involving 1192 participants were enrolled for meta-analysis based on the inclusion and exclusion criteria. The results showed that compared with the group using routine therapies and the group using a single administration of either ulinastatin or Xuebijing, the trial group using Xuebijing combined with ulinastatin was significantly superior in the following aspects: mortality (RR = 0. 54,95% CI (0. 41, 0. 70, P = .000), 7 d APACHE II (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), duration of mechanical ventilation (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), average length of time in the intensive care unit (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), incidence of multiple organ dysfunction syndromes (RR = 0. 54, 95% CI (0.41, 0. 70, P = .000), interleukin-6 (SMD = -1.36,95%CI (-2.46, -0.27), P = .000), lipopolysaccharide (SMD = -9.92, 95%CI (-11.7, -7.90), P = .006), and procalcitonin (SMD = -0.30, 95%CI (-0.34, -0.26), P = .012). CONCLUSIONS: Our results found that Xuebijing when combined with ulinastatin was superior to both routine therapies and the single administration of either ulinastatin or Xuebijing. This finding provides a new therapeutic option for the treatment of sepsis.

An artificial neural network prediction model of congenital heart disease based on risk factors: A hospital-based case-control study.

An artificial neural network (ANN) model was developed to predict the risks of congenital heart disease (CHD) in pregnant women.This hospital-based case-control study involved 119 CHD cases and 239 controls all recruited from birth defect surveillance hospitals in Hunan Province between July 2013 and June 2014. All subjects were interviewed face-to-face to fill in a questionnaire that covered 36 CHD-related variables. The 358 subjects were randomly divided into a training set and a testing set at the ratio of 85:15. The training set was used to identify the significant predictors of CHD by univariate logistic regression analyses and develop a standard feed-forward back-propagation neural network (BPNN) model for the prediction of CHD. The testing set was used to test and evaluate the performance of the ANN model. Univariate logistic regression analyses were performed on SPSS 18.0. The ANN models were developed on Matlab 7.1.The univariate logistic regression identified 15 predictors that were significantly associated with CHD, including education level (odds ratio  = 0.55), gravidity (1.95), parity (2.01), history of abnormal reproduction (2.49), family history of CHD (5.23), maternal chronic disease (4.19), maternal upper respiratory tract infection (2.08), environmental pollution around maternal dwelling place (3.63), maternal exposure to occupational hazards (3.53), maternal mental stress (2.48), paternal chronic disease (4.87), paternal exposure to occupational hazards (2.51), intake of vegetable/fruit (0.45), intake of fish/shrimp/meat/egg (0.59), and intake of milk/soymilk (0.55). After many trials, we selected a 3-layer BPNN model with 15, 12, and 1 neuron in the input, hidden, and output layers, respectively, as the best prediction model. The prediction model has accuracies of 0.91 and 0.86 on the training and testing sets, respectively. The sensitivity, specificity, and Yuden Index on the testing set (training set) are 0.78 (0.83), 0.90 (0.95), and 0.68 (0.78), respectively. The areas under the receiver operating curve on the testing and training sets are 0.87 and 0.97, respectively.This study suggests that the BPNN model could be used to predict the risk of CHD in individuals. This model should be further improved by large-sample-size research.

A discriminant analysis prediction model of non-syndromic cleft lip with or without cleft palate based on risk factors.

BACKGROUND: A risk prediction model of non-syndromic cleft lip with or without cleft palate (NSCL/P) was established by a discriminant analysis to predict the individual risk of NSCL/P in pregnant women. METHODS: A hospital-based case-control study was conducted with 113 cases of NSCL/P and 226 controls without NSCL/P. The cases and the controls were obtained from 52 birth defects' surveillance hospitals in Hunan Province, China. A questionnaire was administered in person to collect the variables relevant to NSCL/P by face to face interviews. Logistic regression models were used to analyze the influencing factors of NSCL/P, and a stepwise Fisher discriminant analysis was subsequently used to construct the prediction model. RESULTS: In the univariate analysis, 13 influencing factors were related to NSCL/P, of which the following 8 influencing factors as predictors determined the discriminant prediction model: family income, maternal occupational hazards exposure, premarital medical examination, housing renovation, milk/soymilk intake in the first trimester of pregnancy, paternal occupational hazards exposure, paternal strong tea drinking, and family history of NSCL/P. The model had statistical significance (lambda = 0.772, chi-square = 86.044, df = 8, P < 0.001). Self-verification showed that 83.8 % of the participants were correctly predicted to be NSCL/P cases or controls with a sensitivity of 74.3 % and a specificity of 88.5 %. The area under the receiver operating characteristic curve (AUC) was 0.846. CONCLUSIONS: The prediction model that was established using the risk factors of NSCL/P can be useful for predicting the risk of NSCL/P. Further research is needed to improve the model, and confirm the validity and reliability of the model.

Congenital anomalies in children exposed to antithyroid drugs in-utero: a meta-analysis of cohort studies.

BACKGROUND: Hyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero. METHODS: Embase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I2 tests. RESULTS: Eight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively. CONCLUSIONS: The meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.

Development of a thyroid hormone receptor targeting conjugate.

Molecular conjugates of hormone receptor-ligands with molecular probes or functional domains are finding diverse applications in chemical biology. Whereas many examples of hormone conjugates that target steroid hormone receptors have been reported, practical ligand conjugates that target the nuclear thyroid hormone receptor (TRbeta) are lacking. TR-targeting conjugate scaffolds based on the ligands GC-1 and NH-2 and the natural ligand triiodothyronine (T3) were synthesized and evaluated in vitro and in cellular assays. Whereas the T3 or GC-1 based conjugates did not bind TRbeta with high affinity, the NH-2 inspired fluorescein-conjugate JZ01 showed low nanomolar affinity for TRbeta and could be used as a nonradiometric probe for ligand binding. A related analogue JZ07 was a potent TR antagonist that is 13-fold selective for TRbeta over TRalpha. JZ01 localizes in the nuclei of TRbeta expressing cells and may serve as a prototype for other TR-targeting conjugates.

The new biomimetic chemistry: artificial transcription factors.

While many research programs have focused on the challenge of developing small molecules that can inhibit protein-protein interactions, some researchers have taken the problem one step further by attempting to develop small molecules that mimic the essential features of an entire protein. An area of particular interest has been in the field of artificial transcription factors (ATFs), where the essential function of some transcription factors is to recruit and promote the assembly of a larger transcription complex, leading to the expression of a gene of interest. The goal of synthesizing small-molecule ATFs holds promise as a means to independently control the expression of genes such as those that are misregulated in cancer and disease.