Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study.

BACKGROUND: Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT). METHODS: A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values. RESULTS: Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04-0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64-13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L). CONCLUSIONS: For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

Prenatal phthalate exposure and neurodevelopmental differences in twins at 2 years of age.

BACKGROUND: Previous studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors. METHODS: A co-twin control design was employed to test whether prenatal phthalate exposure was associated with children's neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility. RESULTS: Maternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (ß = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (ß = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins. CONCLUSIONS: Neurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.

Gender differences in prevalence and clinical correlates of anxiety in first-episode and drug-naïve patients with major depressive disorder comorbid with metabolic syndrome.

BACKGROUND: Although gender differences in major depressive disorder (MDD) have been widely reported, there has not been much focus on gender differences in comorbidity. In patients with MDD and comorbid metabolic syndrome (Mets), the goal of this study was to investigate potential gender differences in the prevalence and clinical correlates of concomitant anxiety. METHODS: Seven hundred and ninety-four first-episode and drug-naïve patients (FEDN) patients with MDD and comorbid Mets were recruited. For each patient, sociodemographic data, thyroid function indicators, and Mets parameters were acquired. Each participant completed the 14-item Hamilton Assessment Scale for Anxiety (HAMA) and the 17-item Hamilton Assessment Scale for Depression (HAMD). RESULTS: There were no gender differences in the prevalence of anxiety in patients with MDD and comorbid Mets. Female patients with MDD had a shorter duration of illness. Correlation analysis showed that HAMD score, TSH, TgAb, and TPOAb were associated with anxiety prevalence in female patients, whereas anxiety onset in male patients was only associated with TSH, TgAb, and TPOAb levels. In addition, multiple logistic regression analysis showed that TSH and TgAb predicted anxiety in male patients, whereas HAMD score and age of onset significantly predicted anxiety in female patients. LIMITATIONS: Cross-sectional design and no control for anxiety-related factors. CONCLUSIONS: Our study showed no gender differences in the prevalence of anxiety in patients with MDD and comorbid Mets. HAMD score was associated with anxiety in female patients, whereas TSH, TgAb, and TPOAb were associated with anxiety in male patients.

Prenatal exposure to poly- and perfluoroalkyl substances and postpartum depression in women with twin pregnancies.

BACKGROUND: Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. OBJECTIVE: To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. METHODS: Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. RESULTS: Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. CONCLUSIONS: The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.

Psychiatric disorders associated with PCSK9 inhibitors: A real-world, pharmacovigilance study.

BACKGROUND: The relationship between Protein Convertase Subtilisin Kexin Type 9 inhibitor (PCSK9i) and psychiatric adverse events (AEs) remains unclear due to the limitations of clinical trials. In this study, PCSK9i-related psychiatric AEs were realistically observed and systematically summarized in the real world by data mining the FDA AE Reporting System (FAERS). METHOD: Total AEs between the third quarter of 2015 and the first quarter of 2023 were obtained from FAERS. Psychiatric AEs were identified using disproportionality analysis and clinical prioritization of signals using a rating scale, followed by univariate logistic regression to explore factors influencing psychiatric AEs. RESULTS: Psychiatric AEs accounted for 6.7% of the total number of PCSK9i reports. Eighteen psychiatric AEs were defined as PCSK9i-related psychiatric adverse events (ppAEs) (lower 95% CI of both ROR >1 and IC025 > 0). The median age of ppAE reports was 68 years, and female patients accounted for 22.67% of reports, including 41.40% of reports with a serious outcome. Eleven (61.11%) and seven (38.89%) ppAEs were classified as weak and moderate clinical priority, respectively. The median time to onset of ppAEs was 149 and 196 days after treatment with evolocumab and alirocumab, respectively. Patients weighing ≥80 kg were 1.59 times more likely to experience ppAEs. CONCLUSION: The results of this study facilitate the prioritization of psychiatric AE signals by healthcare professionals with the goal of mitigating the risk of PCSK9i-related psychiatric AEs. However, as an exploratory study, our findings need to be confirmed in large-scale prospective studies.

A co-twin control study of in utero exposure to poly- and perfluoroalkyl substances and associations with neonatal thyroid-stimulating hormone.

Research quantifying associations between early-life exposure to poly- and perfluoroalkyl substances (PFAS) and neonatal thyroid hormone levels is limited and reports inconsistent results. This study aimed to examine the associations of in utero PFAS exposure with neonatal thyroid-stimulating hormone (TSH), and to verify whether genetic and familial factors contribute to these associations. Within Wuhan Twin Birth Cohort study, we included 148 mother-twin pairs recruited between March 2016 and January 2018. Maternal plasma PFAS concentrations were measured at three different trimesters and averaged. Additionally, we measured cord plasma PFAS concentrations for twin newborns and retrieved their TSH levels from the medical system. Multivariable linear regression, generalized estimation equation, and linear mixed models were used to examine the covariate-adjusted associations. For maternal PFAS analyses, a 2-fold increment of average maternal perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) concentrations was linked with a 15% (95% CI: 2.5%, 28%) and 14% (95% CI: 2.4%, 28%) increase in neonatal TSH, respectively. For twin newborns discordant for PFAS exposure, a 2-fold increment of cord plasma PFOA, PFDA, perfluoroundecanoic acid (PFUdA), and perfluorohexanesulfonic acid (PFHxS) concentrations was related to a 7.1% (95% CI: 0.31%, 14%), 12% (95% CI: 4.8%, 20%), 7.5% (95% CI: 0.30%, 15%), and 8.5% (95% CI: 3.0%, 14%) increase in TSH among twins as individuals, respectively. Although these associations were mainly observed between twin pairs, certain PFAS exposure might have an independent association with increased TSH. Our present study suggests that higher maternal and cord plasma PFAS concentrations are associated with increased neonatal TSH, and genetic and familial factors contribute to these associations.

Clinical correlates and metabolic indicators of elevated fasting glucose in overweight/obese Chinese Han patients with first-episode and drug-naive major depressive disorder.

Background: Overweight/obese major depressive disorder (MDD) patients have a high probability of developing glucose metabolism disorders; however, the results are inconsistent due to the confounding variables involved in the studies. The purpose of this study was to explore the prevalence and risk factors for elevated fasting glucose in Chinese Han patients with overweight/obese first-episode and drug naïve (FEDN) MDD. Methods: The study used a cross-sectional design and recruited 1718 FEDN MDD patients between the ages of 18 and 60 years. Socio-demographic information, anthropometric data, and biochemical parameters were collected. The 17-item Hamilton Assessment Scale for Depression (HAMD), the 14-item Hamilton Anxiety Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) positive subscale were used to assess symptoms of all patients. Results: MDD patients with elevated fasting glucose had higher TSH, TPOAb, TC, TG, LDL-C, systolic and diastolic blood pressure levels than those with normal fasting glucose. Logistic regression analysis showed that age, TSH, TgAb, TPOA, and TG were related factors for elevated fasting glucose, while TSH and combination all these five parameters had the potential to differentiate between patients with elevated fasting glucose and those with normal fasting glucose. Multifactorial regression analysis showed that TSH, TG, and LDL-C were independently associated with elevated fasting glucose. Conclusion: Our findings suggest a high prevalence of elevated fasting glucose in overweight/obese FEDN MDD patients. Several clinically relevant factors and metabolic parameters are associated with elevated fasting glucose in overweight/obese FEDN MDD patients. Limitation: Due to the cross-sectional design, no causal relationship could be derived.

Protein powder supplementation in early pregnancy and the risk of gestational diabetes mellitus: a prospective cohort study.

Objective: Protein powder has attracted attention due to its possible adverse effects. We aimed to investigate the association of protein powder supplementation in early pregnancy with gestational diabetes mellitus (GDM) risk. Methods: We included 6897 participants with singleton pregnancies from a prospective birth cohort. Protein powder supplementation and GDM relationships were examined by unadjusted and multivariable analysis, 1 : 2 propensity score matching, and inverse probability weighting (IPW). A multinomial logistic regression model was used to further explore the effects of protein powder supplementation on the risk of GDM subtypes. Results: Overall, 14.6% of pregnant women (1010) were diagnosed with GDM. In the crude and multivariable analysis before propensity score matching, participants who had received protein powder supplements were more likely to have GDM than women who did not (OR, 1.39 [95% CI: 1.07-1.79]; OR, 1.32 [95% CI: 1.01-1.72]). Protein powder supplementation was significantly associated with a higher GDM risk on IPW analysis (OR, 1.41 [95% CI, 1.08-1.83]), propensity score matching analysis (OR, 1.40 [95% CI, 1.01-1.93]) and multivariable analysis adjusted for propensity score (OR, 1.53 [95% CI, 1.10-2.12]). In the multinomial logistic regression model, protein powder supplementation was only positively associated with the risk of GDM with isolated fasting hyperglycaemia (IFH) in the crude and multivariable models (OR, 1.87 [95% CI: 1.29-2.73]; OR, 1.82 [95% CI: 1.23-2.68]). Conclusions: Protein powder supplementation in early pregnancy is significantly associated with a greater risk of GDM, especially for GDM-IFH. Additional comparative studies are needed to validate these findings.

Piperine ameliorates psoriatic skin inflammation by inhibiting the phosphorylation of STAT3.

Psoriasis is a common chronic inflammatory skin disease that is easy to relapse and difficult to cure. Piperine is the main alkaloid extracted from black pepper, and its role in psoriasis has not been previously reported. We identified that piperine ameliorated M5-induced psoriatic skin lesions. Furthermore, piperine alleviated psoriasis pathological features including epidermal hyperplasia and inflammatory cell infiltration, decreased the expression of psoriasis-characteristic cytokines, chemokines and proteins in IMQ-induced psoriasiform dermatitis. Moreover, we determined that piperine inhibited the phosphorylation of STAT3 in M5- and IMQ-induced psoriasis-like skin lesions. Our data demonstrated that piperine ameliorated psoriatic skin inflammation by inhibiting the phosphorylation of STAT3. Therefore, piperine may be one potential compound candidate for psoriasis therapy, providing new strategies for clinical intervention.

Hexafluoroisopropanol-based deep eutectic solvents for high-performance DNA extraction.

In this study, hexafluoroisopropanol (HFIP)-based deep eutectic solvents (DESs) were developed and used for DNA extraction from human whole blood samples for the first time. HFIP-based DESs were prepared using HFIP and choline chloride (ChCl)/tetrabutylammonium chloride/cetyltrimethylammonium bromide as the hydrogen bond donor and acceptor, respectively. The two-phase system formation was promoted with different inorganic salts as the phase-forming component. According to the strong phase separation capability and high DNA extraction efficiency, DESs consisting of HFIP/ChCl-(NH4)2SO4, HFIP/ChCl-Na2SO4 and HFIP/ChCl-MgSO4 were then selected for application in DNA extraction. The factors that could have impacted the DNA extraction process, including molar ratio of DES, DES addition, salt species and addition, and sample pH, were systematically investigated via single-factor experimental analysis. Furthermore, we selectively examined bovine serum albumin and RNA to assess the specificity of the HFIP-based DESs for DNA extraction. Conclusively, 93.9%, 96.7% and 99.8% DNA could be extracted using the HFIP/ChCl-(NH4)2SO4, HFIP/ChCl-Na2SO4, and HFIP/ChCl-MgSO4 systems, respectively. Moreover, the developed systems were successfully used to extract DNA from human whole blood with satisfactory results. The DNA secondary structure was stable after DES extraction with the electrostatic interaction between DES and DNA as the main force driving DNA adsorption by DES.

Removal of As(III) using a microorganism sustained secrete laccase-straw oxidation system.

While laccase oxidation is a novel and promising method for treating arsenite-containing wastewater, the high cost and unsustainability of commercially available enzymes indicate a need to investigate more cost-effective viable alternatives. Here, a microorganism sustained secrete laccase-straw oxidation system (MLOS) was established and subsequently evaluated for the removal of As(III). MLOS showed efficient biological As(III) oxidation, with an As(III) removal efficiency reaching 99.9% at an initial As(III) concentration of 1.0 mg·L-1. IC-AFS and XPS analysis showed that As(III) was partially oxidized to As(V), and partially As(III) adsorbed on the surface of rice straw. FTIR analysis revealed that hydroxyl, amine and amide groups were all involved in the As(III) removal process. SEM-EDS demonstrated that the surface structure of rice straw was destroyed following Comamonas testosteroni FJ17 (C. testosteroni FJ17) treatment, and the metal ions binding sites of rice straw were increased resulting in elemental arsenic being detected on the material surface. Molecular docking revealed the interaction between key residues of laccase and As(III). Laccase activity was negatively correlated with Cu(II) concentration in the As(III) oxidation. EEM showed that humic-like acids were also involved in the interaction with As(III). Overall, a MLOS derived from biomass waste has a significant potential to be developed as a green and sustainable technology for the treatment of wastewater containing As(III).

Exposure to bisphenols, parabens and phthalates during pregnancy and postpartum anxiety and depression symptoms: Evidence from women with twin pregnancies.

BACKGROUND: Women are vulnerable to suffer from the common mental disorders like anxiety and depression during the postpartum period. Exposure to bisphenols, parabens, and phthalates has been linked to anxiety and depression symptoms in the general population. However, little is known about their impacts on postpartum women. OBJECTIVE: To evaluate the effects of individual and joint exposure to 11 nonpersistent chemicals during pregnancy on postpartum anxiety and depression. METHODS: Among 278 mothers from the Wuhan Twin Birth Cohort (WTBC), bisphenols, parabens, and phthalate metabolites were measured in maternal urine samples from each trimester. Self-rating Anxiety Scale (SAS) and Edinburgh Postnatal Depression Scale (EPDS) were administrated at early pregnancy and 1 month and 6 months postpartum to determine anxiety and depression symptoms, respectively. Associations between urinary chemical biomarkers (individual or mixtures) and anxiety and depression symptoms were estimated using multiple informant model and quantile-based g-computation. RESULTS: With adjustment for confounders, one quartile increase in the overall chemical mixture (bisphenols, parabens and phthalate metabolites) during the second trimester was associated with 1.03-point (95% CI: 0.07, 1.99, P = 0.036) higher EPDS score at 1 month postpartum, in which bisphenol A (BPA) and bisphenol F (BPF) contributed the most to the positive association. Consistent effects were also observed in the multiple informant models. We found that second-trimester BPA and BPF exposure individually showed the strongest and significant associations with anxiety and depression symptoms, and some of associations differed across trimesters (Ptrimester-int < 0.05). CONCLUSIONS: Second-trimester nonpersistent chemical exposure was associated with increased postpartum anxiety and depression symptoms.

Maternal paraben exposure and intra-pair thyroid-stimulating hormone difference in twin neonates.

Thyroid hormones are essential for fetal growth and neurodevelopment. The recent frequent use of parabens has raised concerns about their endocrine-disrupting potential. However, the effects of maternal paraben exposure on neonatal thyroid hormone levels are still largely unknown. In our study, a co-twin control design was employed to analyze the relationships between maternal paraben exposure and neonatal thyroid-stimulating hormone (TSH) difference. We collected information from 252 mother-twin pairs from a twin birth cohort in Wuhan, China. Concentrations of six parabens were measured in maternal urine samples collected at < 16, 16-28, and > 28 weeks of gestation. Data of neonatal TSH levels were retrieved from medical records. Multiple informant models were applied to explore the time-specific relationships between paraben exposure and intra-twin TSH difference and to determine the susceptible window of exposure. We found that maternal urinary methyl paraben (MeP) during early pregnancy was positively associated with intra-twin TSH difference (%change = 5.96 %; 95 % confidant interval (CI): 0.04 %, 12.2 %). However, no significant differences were observed for exposure to ethyl paraben (EtP) and propyl paraben (PrP), and the associations between parabens and intra-twin TSH difference did not differ materially across pregnancy. Further, a stratified analysis based on twin zygosity and chorionicity and sex types indicated that the positive association between early pregnancy MeP exposure and intra-twin TSH difference was significant in monochorionic diamniotic (MCDA) twins of female-female fetuses and dichorionic diamniotic (DCDA) twins of opposite-sex. The prospective twin study provides first evidence that MeP exposure in early pregnancy was associated with an increased TSH difference in twin neonates, especially in female fetuses.

Prenatal exposure to perfluorooctane sulfonate alternatives and associations with neonatal thyroid stimulating hormone concentration: A birth cohort study.

BACKGROUND: Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA) and perfluorobutane sulfonate (PFBS), used as perfluorooctanesulfonate (PFOS) alternatives, were indicated as thyroid hormone disruptive toxicants in experimental studies. However, it is unclear whether prenatal exposure to Cl-PFESA and PFBS affects neonatal thyroid stimulating hormone (TSH) in human. OBJECTIVE: To disclose the relationships between prenatal Cl-PFESAs and PFBS exposure and neonatal thyroid-stimulating hormone (TSH) levels based on a perspective cohort study. METHODS: A total of 1015 pairs of mother and newborn were included from an ongoing birth cohort study in Wuhan, China, between 2013 and 2014. Six PFASs in cord blood sera and TSH concentration in neonatal postpartum heel sticks blood were quantified. Mixed linear and weighted quantile sum (WQS) regression models were applied to assess the individual and combination effects of PFASs exposure on neonatal TSH levels with multiple covariates adjustments. RESULTS: After adjusting for potential confounders and other five PFASs, for each 1-ng/mL increase of PFBS or 8:2 Cl-PFESA, was negatively associated with 25.90% (95%CI: 37.37%, -12.32%; P < 0.001) and 27.19% (95%CI: 46.15%, -1.55%; P = 0.033) change in TSH in male but not female infants, respectively. No significant association was found between other PFASs exposure and neonatal TSH. Higher PFAS mixture in cord blood was significantly associated with decrease TSH concentration in all newborns (ß = -0.36; 95%CI: 0.58, -0.13; P = 0.001) identified by WQS regression model. PFBS, PFOS and 6:2 Cl-PFESA were the major contributors to the neonatal TSH decrement with the weights of 56.50%, 18.71%, 12.81% among PFAS mixture, respectively. CONCLUSIONS: our prospective cohort study suggested a negative association of cord serum PFBS and 8:2 CI-PFESA with TSH concentration in newborns, especially for boys. Additional studies are required to elaborate on the underlying biological mechanisms, especially for PFBS.

Behavioral problems of pediatric patients recovered from COVID-19 in Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is profoundly affecting lives around the globe. Previous studies on COVID-19 mainly focused on epidemiological, clinical, and radiological features of patients with confirmed infection. Little attention has been paid to the follow-up of recovered patients. As a vulnerable population to adverse events, the health status of the COVID-19 recovered pediatric patients is of great concern. We aimed to investigate the prevalence of behavioral problems among pediatric patients recovered from the COVID-19 in Wuhan, China. METHODS: A total of 122 children who were suspected or confirmed COVID-19 cases and hospitalized for treatment were enrolled in the study between April 2020 and May 2020 in Wuhan, China. We collected related information about hospitalization and discharge of the children and emotional symptoms of their parents through electronic medical records and questionnaire. The behavioral problems of children were examined by applying the parent-reported the Strengths and Difficulties Questionnaire (SDQ). RESULTS: The participant children were discharged from hospital after about two months. Among them, 76 (62%) were boys, and the mean age was 6.71 years old. The highest prevalence of behavioral problems among pediatric children with COVID-19 was for prosocial behavior (15%), followed by total difficulties (13%), emotional symptoms (11%), hyperactivity (10%), conduct problems (9%), and peer problems (1%). With regarding to their parents, 26% reported having symptoms of anxiety and 23% as having symptoms of depression. The scores of SDQ were higher in those children whose parents have emotional problems compared to parents without. CONCLUSION: Long-term follow up studies on the psychological and behavioral problems of COVID-19 recovered children and their parents are warranted.

HPV E7 affects the function of cervical cancer cells via the TAL1/lnc­EBIC/KLHDC7B axis.

High­risk human papillomavirus (HPV)16 and 18 are the primary cause of cervical cancer (CC) and long non­coding RNAs (lncRNAs/lncs) are often abnormally expressed in patients with CC. The authors' previous study indicated that oncogenic enhancer of zeste homolog 2 (EZH2)­binding lncRNA in cervical cancer (lnc­EBIC) serves a role in the tumorigenic activity of the HPV E6 protein in patients with CC. However, whether HPV E7 affects the development of CC through lnc­EBIC, and the potential mechanisms underlying this remains unclear. Therefore, the present study investigated the effects of lnc­EBIC and HPV E7 in cervical cancer cell lines HeLa, CaSki and C33A in vitro. CCK­8, EdU and DAPI staining assays, flow cytometry, RT­qPCR, western blotting and Transwell assay were performed on these cell lines. The results revealed that exogenous expression of HPV16/18 E7 significantly promoted lnc­EBIC expression, and conversely, lnc­EBIC was downregulated by silencing endogenous HPV16/18 E7 expression in corresponding CaSki and HeLa cells. Overexpression of lnc­EBIC significantly increased cellular proliferation, migration and invasion, and inhibited apoptosis in HPV­ C33A cells. The tumorigenic effects of HPV16/18 E7 in corresponding CaSki and HeLa cells were significantly blocked by the silencing of lnc­EBIC expression. Molecular analysis revealed that HPV16/18 E7 depended on TAL BHLH transcription factor 1, erythroid differentiation factor inhibition to promote lnc­EBIC expression, which also resulted in the upregulation of oncogenic Kelch domain­containing 7B (KLHDC7B) in corresponding CaSki and HeLa cells. Additionally, KLHDC7B knockdown blocked the tumor­promotive effects of lnc­EBIC in HPV­ C33A cells. Collectively, the results of the present study indicated that lnc­EBIC acts as an oncogenic lncRNA by enhancing KLHDC7B expression in HPV+ and HPV­ CC cells, and can be exploited by HPV16/18 E7 to accelerate tumorigenic activity in CC. These results further revealed that the lnc­EBIC/KLHDC7B axis represents a novel molecular mechanism and potential therapeutic target for CC.

Association between vaccinations and clinical manifestations in children with COVID-19.

BACKGROUND: The infection rate of Coronavirus Disease 2019 (COVID-19) in children was less than that in adults. However, the underlining reason is not well known. METHODS: Children with COVID-19 were recruited from two Children's Hospitals in Wuhan and Shanghai in this case-control study. The associations of initial symptoms with age, vaccinations of Bacillus Calmette Guerin (BCG), and influenza and pathogens were determined by Chi-square t-test. RESULTS: We evaluated 248 confirmed cases, and 56 suspected cases with COVID-19. The median age was 6.82 years old, and 118 cases (38.82%) were girls. Furthermore, 30.26% of all patients were asymptomatic cases. The percentage of asymptomatic cases vaccinated with BCG was not significantly higher than that without BCG vaccination [86/280 (30.71%) vs. 6/13 (46.15%), P=0.203], and initial symptoms were not related with immunized influenza vaccine (P=0.267). Compared to parameters in pediatric patients with normal body temperatures, patients with fever had higher C reactive protein (CRP) (P<0.001). CONCLUSIONS: Pediatric COVID-19 patients with BCG vaccinations exhibit similar clinical manifestations compared to those without BCG vaccinations, and the severity of symptoms in pediatric patients may be related to the maturity of immune function.

Viral loads in throat and anal swabs in children infected with SARS-CoV-2.

Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay on anal swabs was recently reported to be persistently positive even after throat testing was negative during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, data about the consistent performance of RT-PCR assay on throat and anal swabs remain limited in paediatric patients. Here, we retrospectively reviewed RT-PCR-testing results of 212 paediatric patients with suspected SARS-CoV-2 infection at Wuhan Children's Hospital. The diagnostic potential of these two types of specimens showed significant difference (positive rate: 78.2% on throat swabs vs. 52.6% on anal swabs, McNemar Test P = 0.0091) and exhibited a weak positive consistency (Kappa value was 0.311, P < 0.0001) in paediatric patients. Furthermore, viral loads detected on both throat and anal swabs also showed no significant difference (P = 0.9511) and correlation (Pearson r = 0.0434, P = 0.8406), and exhibited an inconsistent kinetic change through the course of SARS-CoV-2 infection. Besides, viral loads in the throat and anal swabs were correlated with different types of immune states, immune-reactive phase, and the resolution phase/immunologic tolerance, respectively. These findings revealed that RT-PCR-testing on throat and anal swabs showed significant difference for monitoring SARS-CoV-2 infection and correlated with different immune state in paediatric patients.

Effects of a HAPA-based multicomponent intervention to improve self-management precursors of older adults with tuberculosis: A community-based randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a multicomponent intervention based on the Health Action Process Approach (HAPA) model to improve the self-management precursors of older adults with tuberculosis (TB). METHODS: A cluster-randomised controlled trial was conducted. Older adults with TB in the intervention communities received HAPA-based multicomponent interventions at the beginning of treatment and in the first and sixth months after treatment initiation, and those in the control communities received health education alone. Self-management precursors were measured at baseline and 1 week after each intervention. RESULTS: Among 262 randomized patients, 244 (93%) completed the trial. Compared with the control group, self-management precursor scores for the intervention group increased significantly over time (ßgroup*time = 2.92, p < 0.001) in the following 3 precursors: behaviour belief (ßgroup*time = 0.35, p < 0.001), behaviour plan (ßgroup*time = 0.72, p < 0.001), and self-efficacy (ßgroup*time = 1.85, p < 0.001). Education was significantly associated with behaviour belief (ß = 0.18, p < 0.05). Chronic comorbidity was significantly associated with behaviour plan (ß=-0.26, p < 0.05). CONCLUSION: Compared with single health education, the HAPA-based multicomponent interventions significantly improved the self-management precursor of older adults with TB. PRACTICE IMPLICATIONS: This HAPA-based multicomponent intervention strategy may be a promising self-management mode for the routine health care of TB patients.

[Genome-wide copy number microarray analysis for a boy with autism].

OBJECTIVE: To carry out genome-wide copy number variations (CNVs) analysis for a boy with autism by using single nucleotide polymorphism array (SNP array). METHODS: SNP array analysis was conducted for the boy and his parents, and the data was validated by real-time PCR. Correlation between the deleted genes and the phenotype was analyzed by reviewing the literature. RESULTS: The patient was found to carry a terminal deletion of 18q22.3q23 (7.1 Mb), which involved FBXO15, ZNF407, ZADH2, TSHZ1, MBP and ADNP2 genes. No pathogenic CNVs were found in the parents. Comparison of the patient with cases reported in the literature suggested that the ZNF407 gene probably accounts for the autistic phenotype in these patients. CONCLUSION: The autistic phenotype of the patient may be attributed to the 18q deletion, for which ZNF407 may be a critical candidate. SNP array has provided an useful tool for the study of molecular mechanism underlying autism.